1. Please summarise this article.
This trail has demonstrated the management of post-transplant recipient infected with COVID.
The most common feature presenting feature was fever, cough and other constitutional symptoms,
Laboratories shows high CRP, lymphonia, and high ferritin level.
The management strategy was general management, discontinuation of immunosuppression, there other treatment option, dexamethasone, tocilizumab, baricitinib and casirivimab and imdevimab. 2. What is the level of evidence provided by this article?
Level of evidence IV 3. What is meant by the impact factor of a journal?
Impact factor demonstrated that how the article was cited.
This is a serial case reports of 8 patients . all of them are kidney transplant recipients who acquired COVID19 infection.COVID19 in transplanted patients has the same symptoms in form of fever and cough. So far no observed effects of IS was observed on the course of the disease. The saple size was small . management is mainly supportive . diagnosis is through CXRay. Remdesivir is recommended for treating cases.
Level of evidence is 4 as it is a case series
The impact factor is the number of citation within the last 2 years
Summary of the article COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence Introduction: The new coronavirus (COVID-19) pandemic emerged in December 2019, was highly infectious killing millions of people across globe. There is a common belief that, kidney transplant recipients have higher risk of infection due impact of immunosuppression and associated comorbidities. Course and outcomes of 8 kidney transplant recipients infected with COVID-19 are discussed here. The common features of COVID-19 in KTR: 1. Fever and cough – most common presentation. 2. Lymphopenia, high CRP and ferritin level. 3. HTN – most common co-morbidity. 4. 2 patients had AKI – 1 of them had rising Creatinine, required CVVH. Therapeutic strategies for managing the KTRs with COVID-19 infection: 1. IS reduction – antiproliferative (MMF) discontinued for all. 2. Managed on outpatient basis; 1 patient advised self-isolation at home. 3. Hospital admission to Renal Ward, supportive treatment (IV fluid, monitoring vitals, saturation, RFT, and symptomatic treatment with or without oxygen supplement, based on PaO2) – 6 patients. 4. ICU admission, mechanical ventilation and CVVH – 1 patient. Discussion: 1. Early studies reported – low incidence of AKI (3–9%). 2. Recent study by Cheng et al, showed a higher frequency of renal abnormalities among 710 patients – · 44% had proteinuria. · 26.7% had haematuria. · 14.1% had high serum Cr. 3. The pathophysiology of renal involvement is still unclear, but theories suggested are cytokine storm syndrome and direct renal injury by the virus. 4. Diagnosis and laboratory features of COVID-19 infection: · Low lymphocyte / white blood cell ratio had fatal outcomes. · High CRP (60.7%) is linked to unfavourable outcome – ARDS, myocardial damage and death. · Higher serum ferritin is associated with ARDS development and death. · High IL-6 levels (52%) – novel biomarker, a/w increased risk of mortality in COVID-19 Imaging: CXR – may show patchy consolidation; HRCT chest to be done when there is high clinical suspicion, with CXR normal / uncertain features in seriously ill patient. 5. Management of COVID-19 infection: A. Mild infections: the usual practice is to reduce immunosuppression – withhold antiproliferative suggested. B. Severe infection with requirement to mechanical ventilation: to maintain corticosteroids, hold antiproliferative and to argue about ceasing CNIs. C. Remdesivir-treated patients had 31% faster time to recovery when compared to control. D. CRRT may play a role in the management of AKI in COVID-19 patients. It was assumed that high-volume hemofiltration could remove inflammatory cytokines (tumour necrosis factor, IL-6, and IL-1β) involved in the pathogenesis of renal injury. Level of evidence provided by this article: case series – level of evidence grade 5. The impact factor of a journal: Journal impact factor (JIF) is sciento-metric index calculated by Clarivate, that reflects annual average number of citations of articles published in last 2years. indexed by Clarivate’s Web of Science. Limitations of the JIF · Some journals increase impact factor by reducing the number of scholarly records. · Extension of the impact factor to the assessment of journal quality or individual authors is inappropriate. · Extension of the impact factor to cross-discipline journal comparison is also inappropriate. · Those who choose to use the impact factor as a comparative tool should be aware of the nature and premise of its derivation and also of its inherent flaws and practical limitations.
Dear All You have noticed that I published this article before the publication of the results of the RECOVERY trial. Do you think I would have treated these patients differently? Dear Prof. Ahmad: You have noticed that I published this article before the publication of the results of the RECOVERY trial. Do you think I would have treated these patients differently? “No” for 7 of 8 patient – (mild to moderate illness) : general supportive care was only treatment required; 1 patient was managed even as outpatient. However, 1 patient with severe illness (Cytokine storm Syndrome), required ICU admission, ventilatory support, CVVH. Only this patient would have been treated according to the Recovery Trial regimen (i.e IV dexamethasone 6 mg daily till recovery +/- Tocilizumab) should it be published that time. RECOVERY trial used 4 therapeutic options – dexamethasone, tocilizumab, baricitinib and casirivimab-imdevimab can be used in critically ill COVID patients. Only case 5 having high Serum IL-6, might have been benefitted from Tocilizumab + Dexamethasone, with good cover of antifungal and antimicrobial therapy.
Please summarise this article.
This short series demonstrates experience in managing COVID-19 disease in renal transplant patients in the absence of strong evidence.
The most frequently associated comorbidity was hypertension.
The most common presenting features were fever and cough.
The main radiological investigation was a portable chest X-ray.
Other common features included lymphopenia, high C-reactive protein, and a very high ferritin level.
Management included supportive treatment (intravenous fluid therapy, monitoring renal function, and symptomatic treatment with or without ward-based oxygen therapy depending on oxygen saturation) and discontinuation of the antiproliferative immunosuppressive drugs.
Supportive treatment could be sufficient for the management or to be tried first.
Introduction
In the UK, mortality cases exceeded 30,000 so far. There is a common belief among transplant clinicians that kidney transplant recipients have a high risk of infection due to long-term immunosuppression and associated comorbidities. Data, clinical picture, and outcomes of COVID-19 in kidney transplant recipients are scarce.
Discussion
Many studies showed that COVID-19 infection is associated with high CRP. Guan et al. reported that 60.7% of patients had an elevated CRP, while severe cases had a higher level compared to the non-severe ones (81.5 vs. 56.4% for CRP).
Other reports noticed that high CRP could be linked to unfavourable outcomes, such as ARDS development ,myocardial damage ,and death .
Serum ferritin was measured in only 3 of our patients, and the level was very high. Many reports suggested that higher serum ferritin is associated with ARDS development and death .Ferritin is an acute-phase protein, but we are not sure about the sensitivity and specificity concerning the outcome.
IL-6 is considered a novel biomarker for COVID-19 diagnosis.
Other studies suggested that increased IL-6 levels can be associated with an increased risk of mortality.
there is no clear evidence to support the role of IL-6 blocker (tocilizumab) in treatment of COVID-19 in both transplant and non-transplant population.
The British Society of Thoracic Imaging (BSTI) issued guidelines which state that there is no recommended use of CT unless there is high suspicion with normal or uncertain appearance of CXR in a seriously ill patient .
It is also essential for clinicians of all specialities to be familiar with the radiological findings of COVID-19 on chest X-ray.
Generally speaking, in mild infections, the usual practice is to continue or reduce the dose of immunosuppressive drugs.
we suggest discontinuation of the antiproliferative drugs (azathioprine and mycophenolate mofetil) while monitoring the patients closely.
Remdesivir was used as a compassionate treatment that showed promising results .
Besides, the Adaptive COVID-19 Treatment Trial (NCT04280705) proved that remdesivir-treated patients had 31% faster time to recovery when compared to control .
Based on the previous results, the US Food and Drug Administration has authorized the use of remdesivir as a treatment option for hospitalized COVID-19 patients .
Conclusion
In the above report, the presentations of COVID-19 infected renal transplant patients were not different from the general population where fever and cough were the most frequent symptoms. We believe that our transplant patients did not behave differently from the general population as far as COVID-19 infection is concerned. Because of the small sample size, we could not evaluate the effect of immunosuppression on the course of the disease, but at least it is not a detrimental effect. Based on our experience, supportive treatment could be sufficient or at least to be tried first. It is worth mentioning that the clinical examination supported by simple bedside measures such as oxygen saturation and portable CXR rather than CT scan could be enough and limit the spread of infection. We also found that short hospital stay with self-isolation on discharge reduces the burden on the health service and protect the staff and the public. Since remdisivir was approved for the treatment of COVID-19 and its interaction with CNI is yet unknown, we recommend treatment with remdisivir in a hospital setting where CNI drug level monitoring is available.
What is the level of evidence provided by this article?Level IV
What is meant by the impact factor of a journal? used to measure the frequency with which the “average article” in a journal has been cited in a particular time period, which in turn reflect the potency & importance of the journal. calculated based on a two-year period via dividing the number of citations by the number of citable articles.
Summary of the article COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence Introduction: The new coronavirus (COVID-19) pandemic emerged in December 2019, was highly infectious killing millions of people across globe. There is a common belief that, kidney transplant recipients have higher risk of infection due impact of immunosuppression and associated comorbidities. Course and outcomes of 8 kidney transplant recipients infected with COVID-19 are discussed here. The common features of COVID-19 in KTR: 1. Fever and cough – most common presentation. 2. Lymphopenia, high CRP and ferritin level. 3. HTN – most common co-morbidity. 4. 2 patients had AKI – 1 of them had rising Creatinine, required CVVH. Therapeutic strategies for managing the KTRs with COVID-19 infection: 1. IS reduction – antiproliferative (MMF) discontinued for all. 2. Managed on outpatient basis; 1 patient advised self-isolation at home. 3. Hospital admission to Renal Ward, supportive treatment (IV fluid, monitoring vitals, saturation, RFT, and symptomatic treatment with or without oxygen supplement, based on PaO2) – 6 patients. 4. ICU admission, mechanical ventilation and CVVH – 1 patient. Discussion: 1. Early studies reported – low incidence of AKI (3–9%). 2. Recent study by Cheng et al, showed a higher frequency of renal abnormalities among 710 patients – · 44% had proteinuria. · 26.7% had haematuria. · 14.1% had high serum Cr. 3. The pathophysiology of renal involvement is still unclear, but theories suggested are cytokine storm syndrome and direct renal injury by the virus. 4. Diagnosis and laboratory features of COVID-19 infection: · Low lymphocyte / white blood cell ratio had fatal outcomes. · High CRP (60.7%) is linked to unfavourable outcome – ARDS, myocardial damage and death. · Higher serum ferritin is associated with ARDS development and death. · High IL-6 levels (52%) – novel biomarker, a/w increased risk of mortality in COVID-19 Imaging: CXR – may show patchy consolidation; HRCT chest to be done when there is high clinical suspicion, with CXR normal / uncertain features in seriously ill patient. 5. Management of COVID-19 infection: A. Mild infections: the usual practice is to reduce immunosuppression – withhold antiproliferative suggested. B. Severe infection with requirement to mechanical ventilation: to maintain corticosteroids, hold antiproliferative and to argue about ceasing CNIs. C. Remdesivir-treated patients had 31% faster time to recovery when compared to control. D. CRRT may play a role in the management of AKI in COVID-19 patients. It was assumed that high-volume hemofiltration could remove inflammatory cytokines (tumour necrosis factor, IL-6, and IL-1β) involved in the pathogenesis of renal injury. Level of evidence provided by this article: case series – level of evidence grade 5. The impact factor of a journal: Journal impact factor (JIF) is sciento-metric index calculated by Clarivate, that reflects annual average number of citations of articles published in last 2years. indexed by Clarivate’s Web of Science. Limitations of the JIF · Some journals increase impact factor by reducing the number of scholarly records. · Extension of the impact factor to the assessment of journal quality or individual authors is inappropriate. · Extension of the impact factor to cross-discipline journal comparison is also inappropriate. · Those who choose to use the impact factor as a comparative tool should be aware of the nature and premise of its derivation and also of its inherent flaws and practical limitations.
Dear All You have noticed that I published this article before the publication of the results of the RECOVERY trial. Do you think I would have treated these patients differently? Dear Prof. Ahmad: You have noticed that I published this article before the publication of the results of the RECOVERY trial. Do you think I would have treated these patients differently? “No” for 7 of 8 patient – (mild to moderate illness) : general supportive care was only treatment required; 1 patient was managed even as outpatient. However, 1 patient with severe illness (Cytokine storm Syndrome), required ICU admission, ventilatory support, CVVH. Only this patient would have been treated according to the Recovery Trial regimen (i.e IV dexamethasone 6 mg daily till recovery +/- Tocilizumab) should it be published that time. RECOVERY trial used 4 therapeutic options – dexamethasone, tocilizumab, baricitinib and casirivimab-imdevimab can be used in critically ill COVID patients. Only case 5 having high Serum IL-6, might have been benefitted from Tocilizumab + Dexamethasone, with good cover of antifungal and antimicrobial therapy.
The new coronavirus disease 2019 (COVID-19) infec- tion, emerged in Wuhan city, China, in December 2019, has close genomic structural similarities with the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused the SARS pandemic in 2003 and the middle east respiratory syndrome coronavirus (MERS-CoV) that caused (MERS) epidemic in 2012 [1, 2]. By April 26, 2020, infections related to COVID-19 affected people from 210 countries and caused 203,818 reported deaths worldwide.
In this report, we present our experience with 8 cases of COVID-19 infection in kidney transplant patients from Sheffield Kidney Institute, UK. The median age of patients was 48.5 years (ranging from 21 to 71 years), in- cluding 4 males and 4 females. Three patients had kidney transplantation within the last 3 months, and the rest were transplanted for more than a year.
In our case series, the most frequent presentation was fever (5 patients) and cough (5 patients). Fever was re- ported to be the most common symptom followed by cough . Two large studies demonstrated that 82–87% of their patients had a fever, while patients with cough ranged from 44 to 65.7%
All our patients had lymphopenia and a high CRP lev- el. Guan et al. reported that 83.2% of infected patients had lymphopenia on admission. Another study suggested a link between lymphopenia and acute respiratory dis- tress syndrome (ARDS) development . Two more re- ports demonstrated that patients who had a significantly low lymphocyte/white blood cell ratio both on admission and during hospitalization had fatal outcomes . Many studies showed that COVID-19 infection is associ- ated with high CRP. Guan et al. reported that 60.7% of patients had an elevated CRP, while severe cases had a higher level compared to the non-severe ones (81.5 vs. 56.4% for CRP).
Regarding the management, 6 of our patients had their antiproliferative drugs stopped, and they received sup- portive treatment; 1 patient needed oxygen therapy, and 1 required mechanical ventilation. On the other hand, none of our patients received specific antiviral drugs. When managing immunosuppression in kidney transplant re- cipients, the age, the severity of infection, the post-trans- plant duration, any other associated comorbidity, tissue mismatch, and any episodes of rejection should be consid- ered. Generally speaking, in mild infections, the usual practice is to continue or reduce the dose of immunosup- pressive drugs. While we declare that the small sample size of this study cannot give firm recommendations, we sug- gest discontinuation of the antiproliferative drugs (aza- thioprine and mycophenolate mofetil) while monitoring the patients closely.
We also found that short hospital stay with self-iso- lation on discharge reduces the burden on the health ser- vice and protect the staff and the public. Since remdisivir was approved for the treatment of COVID-19 and its in- teraction with CNI is yet unknown, we recommend treat- ment with remdisivir in a hospital setting where CNI drug level monitoring is available.
Please summarise this article: Introduction: New coronavirus disease 2019 (COVID-19) infection, which is structurally similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV), affected people worldwide but the data regarding this infection among the transplant recipients is lacking. The article deals with 8 kidney transplant recipients infected with COVID-19. Case reports: Patient 1: 21-year-old female, 4 months post-transplant, presented with only fever without any respiratory involvement. Throat/ nasal swab for COVID-19 was positive. She was admitted and given supportive treatment, MMF stopped, and discharged after 2 days. Patient 2: 71-year-old male, 4 years post-transplant, history of colon adenocarcinoma 6 months back and with chronic graft dysfunction, presented with dry cough and x ray chest showed bilateral lung involvement. Throat/ nasal swab for COVID-19 was positive. He was admitted and given supportive treatment, MMF stopped, and discharged after 2 days. Patient 3: 50-year-old male, 2 months post-transplant, history of granulomatous polyangitis, presented with productive cough and a clear x ray chest. COVID-19 test was positive. MMF was stopped. He was advised home isolation and supportive treatment. Patient 4: 63-year-old male, 15 years post-transplant, history of IgA nephropathy, presented with fever and elevated serum creatinine and x ray chest showed bilateral lung involvement. Test for COVID-19 was positive. Blood culture grew staphylococcus aureus, tacrolimus trough levels were low. He was admitted and given supportive treatment with intravenous antibiotics. MMF was stopped while tacrolimus dose was increased, and he was discharged after 7 days. Patient 5: 47-year-old female, 5 months post-transplant, history of bronchial asthma presented with dry cough with shortness of breath and x ray chest showed bilateral lung involvement. Throat/ nasal swab for COVID-19 was positive. Serum creatinine, CRP, IL-2, and ferritin were elevated with urine culture growing E.coli. She was admitted in ICU and given supportive treatment, MMF stopped, and required non-invasive ventilation due to respiratory discomfort, but was intubated in view of worsening respiratory functions. Bronchoalveolar lavage revealed aspergillus. CVVH required in view of worsening renal function. Patient improved after 2 weeks, extubated and shifted to the medical ward from where she was discharged after 1 week. Patient 6: 71-year-old female, 5 years post-transplant, history of diabetes mellitus, presented with fever and x ray chest showed bilateral lung involvement. Throat/ nasal swab for COVID-19 was positive. She was admitted and given supportive treatment, MMF stopped, and discharged after 4 days. Patient 7: 40-year-old female, 3 years post-transplant, history of hypertension, presented with fever and dry cough. Throat/ nasal swab for COVID-19 was positive. She was admitted and given supportive treatment, MMF stopped, and discharged after 4 days. Patient 8: 38-year-old male, 7 years post-transplant, history of chronic graft dysfunction, presented with productive cough and dyspnea for 2 days. Oxygen saturation was low on room air and x ray chest showed bilateral lung involvement. Throat/ nasal swab for COVID-19 was positive. He was admitted and given supportive treatment including oxygen support, tacrolimus dose reduced, azathioprine stopped, prednisolone dose increased, and discharged after 2 days. Discussion: Transplant recipients have increased risk of infection due to underlying CKD, immunosuppression, and presence of co-morbidities like diabetes and hypertension (2-fold risk), and COPD (3-fold risk). The median age of the patients was 48.5 years, with 3 of the patients presenting within 3 months post-transplant.
Most common initial symptoms were fever and cough. 25% of the patients developed acute kidney injury (AKI), with one requiring renal replacement therapy. Renal involvement in COVID-19 is thought to be due to either cytokine storm syndrome, or due to direct viral renal injury. High volume hemofiltration could help by removing inflammatory cytokines.
All patients had lymphopenia and elevated CRP. Lymphopenia has been linked with development of acute respiratory distress syndrome (ARDS)while low lymphocyte/ white blood cell count ratio is associated with increased mortality. Elevated CRP and ferritin have been shown to be associated with ARDS, myocardial damage, and death. Elevated IL-6 has also been shown to be associated with increased mortality.
75% had chest x ray findings. So chest x ray should be the initial imaging of choice with CT reserved for seriously ill patients with uncertain x ray findings. One patient required ward-based oxygen therapy while another required intubation and mechanical ventilation. In mild infections, immunosuppressive drug dose, especially antiproliferative agents can be continued or reduced, while in severe cases calcineurin inhibitors would require cessation. The treatment should be individualized as per the clinical picture of the patient.
Convalescent plasma use as a treatment option is under investigation while remdesivir use has shown promising results with faster recovery in hospitalized patients. Conclusion: COVID-19 presentation in kidney transplant recipients is similar to general population, with fever and cough being the commonest symptoms, and majority of the patients require supportive treatment alone for recovery. Short hospital stay and self-isolation on discharge with remdesivir use in hospitalized patients is advised. 2. What is the level of evidence provided by this article? Level of evidence: Level 4: Case series 3. What is meant by the impact factor of a journal?
Impact factor of a journal implies the average number of citations received per article published in the journal over last 2 years.
Summary of the case series
Transplant clinicians commonly believe that kidney transplant recipients have a high infection risk due to long-term immunosuppression and associated comorbidities. In the absence of firm evidence, this brief series demonstrates experience in managing COVID-19 disease in renal transplant patients. 8 incidences of COVID-19 infection in recipients of kidney transplants The median age is 48.5; the range is 21–71. Sex of patients as follows 4 men and 4 women. Hypertension was the most prevalent associated comorbidity. The two most prevalent symptoms were fever and congestion. The primary radiological examination consisted of a portable chest X-ray. Also prevalent were lymphopenia, a high C-reactive protein level, and a very high ferritin level. One patient was treated as an outpatient, while the remaining seven required hospitalization, one of whom was admitted to the intensive therapy unit. Depending on oxygen saturation, intravenous fluid therapy, monitoring of renal function, and symptomatic treatment with or without ward-based oxygen therapy were administered. Discontinuation of the immunosuppressive antiproliferative medications in all patients Seven patients regained their health and were sent home to self-isolate. One individual required intensive care and mechanical ventilation. None received antiviral therapy or dexamethasone.
Discussion
Multiple risk factors, such as immunosuppression, underlying CKD, and comorbidities, place transplant patients at a high risk of infection. Patients with hypertension and diabetes have a risk of infection that is double that of COPD patients. The pathophysiology of renal involvement is still unknown, but hypotheses point to a cytokine storm syndrome or direct virus-induced renal injury. Continuous renal replacement therapy may be used to treat AKI in COVID-19 patients. Lymphopenia, elevated CRP levels, and elevated ferritin levels are associated with ARDS and poor outcomes. No unambiguous evidence supports the use of the IL-6 blocker tocilizumab in the treatment of COVID-19 in either transplant or nontransplant patients. Clinicians of all specialties must also be conversant with the radiological findings of COVID-19 on chest X-ray. Stop administering the antiproliferative medications (azathioprine and mycophenolate mofetil) while attentively monitoring the patients. In severe cases necessitating mechanical ventilation, discontinue calcineurin inhibitors while continuing corticosteroid treatment.
Conclusions
COVID-19-infected renal transplant recipients do not present differently than the general population. Supportive treatment may be sufficient or should be attempted initially. A brief hospital stay followed by self-isolation reduces the burden on the health service and protects the staff and the general public.
Discharge with full recovery and stable renal function
2.Patient 2
71-year-old, male, Hypertension, 4 years post-transplant complicated with hx of colon adenoca post transplant (prednisolone, tacrolimus, mycophenolate 250 mg BD)
Presented with dry cough
Chest radiograph patchy consolidation
Withhold MMF and supportive care
3.Patient 3
50-year-old, Wegners’ granulomatosis, 2 months post transplant (prednisolone, tacrolimus and mycophenolate 500 mg BD).
Presented with productive cough
Chest radiograph clear
Withhold MMF and supportive care
4.Patient 4
63-year-old, IgA Nephropathy, hypertension, 14 years post kidney transplantation (prednisolone, tacrolimus and mycophenolate 500 mg BD).
Abstract:
Reports of 8 cases of kidney transplant recipients infected with COVID-19 of middle age including 4 males and 4 females. The most frequently associated comorbidity was hypertension and the common presenting features were fever and cough. The main radiological investigation was a portable chest X-ray. Other common features included lymphopenia, high C-reactive protein and a very high ferritin level. Introduction:
The new coronavirus disease 2019 (COVID-19) infection, emerged in Wuhan city, China, in December 2019, has close genomic structural similarities with the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused the SARS pandemic in 2003 and the middle east respiratory syndrome coronavirus (MERS-CoV) that caused (MERS) epidemic in 2012 [1, 2]. By April 26, 2020, infections related to COVID-19 affected people from 210 countries and caused 203,818 reported deaths worldwide. Case report: Patient 1:
A 21-year-old female – who had a deceased donor kidney transplant in December 2019 presented on March 30 with fever (39.2°C).controlled hypertension with on other symptoms COVID-19 +VE treated by supportive care and discontinue MMF. Patient 2:
A 71-year-old male with hypertensive nephropathy who received a kidney graft in February 2016. He had a history of colon adenocarcinoma in June 2019. His baseline Cr was 240–260 μmol/L. covid-19 test is +ve ,treated with supportive management and discontinue MMF. Patient 3:
A 50-year-old male with a history of Wegner’s granulomatosis received a live donor kidney transplant in February 2020. He presented on April 3 with productive cough, and was tested positive for SARS-CoV-2 RNA despite unremarkable clinical examination. . The management included discontinuation of MMF, reduction of tacrolimus dose, and self-isolation at home. He was advised to drink plenty of fluids and report to the unit any new symptoms Patient 4:
A 63-year-old male with a history of IgA nephropathy with a deceased donor kidney transplant in December 2005. He is hypertensive and maintained on calcium channel blockers. He presented on March 20 with fever (38.8°C) and acute kidney injury (AKI; Cr 297 μmol/L, baseline 110 μmol/L). The chest X-ray showed patchy bilateral consolidation, and SARS-CoV-2 RNA was positive. Blood culture was positive for staphylococcus aureus. Serum C-reactive protein (CRP) was 175 mg/L, and serum ferritin was 929 μg/L. treated with IV broad-spectrum antibiotics and paracetamol, stopped MMF and increased the tacrolimus dose. Kidney function tests improved. The patient recovered and discharged. Patient 5:
A47-year-old female with bronchial asthma received a deceased donor kidney transplant in December 2019. c/o dry cough and shortness of breath but no fever. O/E: tachypnoea with a respiratory rate of 36 breaths/min, and the peripheral oxygen saturation was 80%. Investigations: lab shows AKI and mild proteinuria. Chest X-ray revealed bilateral middle and lower zone consolidation. Nose and throat viral swabs for COVID-19 were positive.
patient admitted to the intensive therapy unit (ITU) for non-invasive ventilation . Her respiratory functions got worse, and she required intubation and invasive ventilation.
Bronchoalveolar lavage showed moderate growth of aspergillus. She received broad-spectrum antibiotics and antifungals. No specific antiviral drugs were given.
MMF was discontinued. Her kidney functions deteriorated, and she became anuric; therefore, CVVH was commenced. After 14 days, she was weaned off mechanical ventilation and transferred from the ITU to the medical ward. Her kidney function improved and discharged home. Patient 6:
A 71-year-old female with type II diabetes, received deceased donor kidney transplantation. C/O: fever (38.5°C) and no other complaint. Chest X-ray showed bilateral peripheral mid and lower zone consolidation. Nasal and throat swabs were positive for COVID-19 RNA.
RFT normal, and microbiological tests were negative. She was admitted to the medical ward for adequate hydration and symptomatic treatment. MMF was discontinued and discharged after 4 days with full recovery. Patient 7:
A 40-year-old female with hypertension received deceased donor kidney transplantation. on 10th April. C/O: fever (39°C) and dry cough . Nose and throat swabs for COVID-19 RNA were positive. Kidney function tests were stable and microbiological analyses were negative. Patient admitted for supportive management with IV fluid and paracetamol. MMF was discontinued, with good recovery and discharged home. Patient 8:
A 38-year-old male with a failing kidney transplant from June 2013 presented with productive cough shortness of breath for 2 days. COVID-19 test positive and he was desaturated. Management: discontinuation of azathioprine, reduction of tacrolimus dose, and increase of prednisolone dose to 15 mg OD. He did not require any dialysis. Oxygen saturation recovered to >95% on room air, and the patient was discharged after 2 days. Discussion:
In this report three patients had kidney transplantation within the last 3 months, and the rest were transplanted for more than a year.
The most initial symptoms is fever and cough
Transplant patients are at a high risk of infection due to multiple risk factors, including immunosuppression, underlying CKD, and associated comorbidities.
In mild infection we continue or reduce the immunosuppressive therapy and stopped in severe infection. Conclusion:
In this report COVID-19 presentation like general population in its symptoms .and managed by supportive care first.
we recommend treatment with remdesivir in a hospital setting where CNI drug level monitoring is available.
We recommend treatment with remdisivir in a hospital setting where CNI drug level monitoring is available. Level of evidence is IV
COVID-19 infection structurally similar to SARS-CoV and MERS-CoV. Data regarding this infection among the transplant recipients is still lacking. The article summarized 8 kidney transplant recipients infected with COVID-19.
21-year-old female, 4 months post-KTx, presented with fever without any respiratory involvement. Throat/ nasal swab for COVID-19 was positive, and was admitted. She was given supportive treatment, MMF was stopped, and discharged after 2 days.
71-year-old male, 4 years post-KTx with the history of colon adenocarcinoma 6 months ago and has chronic graft dysfunction. He presented with dry cough and chest x ray showed bilateral lung involvement. The swab for COVID-19 was positive. He was admitted and given supportive treatment, MMF stopped, and discharged after 2 days.
50-year-old male, 2 months post-KTx with the history of GPA, presented with productive cough and with a clear x ray chest. COVID-19 test was positive. MMF was stopped. He was advised for home isolation and treated with supportive treatment.
63-year-old male, 15 years post-KTx with IgA nephropathy, presented with fever and elevated serum creatinine. Chest x ray showed bilateral lung involvement. COVID-19 test was positive however blood culture grew staphylococcus aureus. His tacrolimus trough levels were low. He was admitted and given supportive treatment along with intravenous antibiotics. MMF was stopped while tacrolimus dose was increased to match the desired level. He was discharged after 7 days.
47-year-old female, 5 months post-KTx with bronchial asthma, presented with dry cough with shortness of breath and chest x ray showed bilateral lung involvement. The swab for COVID-19 was positive. Serum creatinine, CRP, IL-2, and ferritin were elevated with urine culture grew E.coli. She was admitted in ICU and required non-invasive ventilation due to respiratory discomfort. She given supportive treatment and MMF was stopped. BAL revealed aspergillus. CVVH for worsening renal function. She improved after 2 weeks and she was discharged after 1 week.
71-year-old female, 5 years post-KTx, with diabetes mellitus, presented with fever and chest x ray showed bilateral lung involvement. She was positive for COVID-19 .She was admitted, given supportive treatment, MPA was stopped and discharged after 4 days.
40-year-old female, 3 years post-KTX with hypertension, presented with fever and dry cough. She was COVID-19 positive. She was given supportive treatment, while MMF was stopped. She was discharged after 4 days.
38-year-old male, 7 years post-KTx, with history of chronic graft dysfunction, presented with productive cough and dyspnea for 2 days. Oxygen saturation was low on room air and chest x ray showed bilateral lung involvement. Swab for COVID-19 was positive. He was admitted and given supportive treatment including oxygen support, tacrolimus dose wasreduced, azathioprine stopped, prednisolone dose increased, and discharged after 2 days.
KTR have increased risk of infection due to underlying CKD, immunosuppression, and presence of co-morbidities like diabetes and hypertension (2-fold risk), and COPD (3-fold risk). The median age was 48.5 years. 3 patients presenting within 3 months post-transplant.
Most common initial symptoms were fever and cough. 25% of the patients developed acute kidney injury (AKI), with one requiring renal replacement therapy. Renal involvement in COVID-19 is thought to be due to either cytokine storm syndrome, or due to direct viral renal injury. High volume hemofiltration could help by removing inflammatory cytokines.
All patients had lymphopenia and elevated CRP. Lymphopenia has been associated with development of ARDS while low lymphocyte/ WBC count ratio is associated with increased mortality. Elevated CRP and ferritin have been shown to be associated with ARDS, myocardial damage, and death. Elevated IL-6 has also been shown to be associated with increased mortality.
75% had chest x ray findings. So chest x ray should be the initial imaging of choice with CT reserved for seriously ill patients with uncertain x ray findings.
In mild infections, immunosuppressive drug dose, especially antiproliferative agents can be continued or reduced, while in severe cases CNI would require cessation. The treatment should be individualized as per the clinical picture of the patient.
Convalescent plasma use as a treatment option is under investigation while remdesivir use has shown promising results with faster recovery in hospitalized patients.
COVID-19 presentation in KTR is similar to general population, with fever and cough being the commonest symptoms, and majority of the patients require supportive treatment alone for recovery.
Short hospital stay and self-isolation on discharge with remdesivir use in hospitalized patients is advised.
What is the level of evidence provided by this article?
Level 4: Case series
What is meant by the impact factor of a journal?
Impact factor of a journal implies the average number of citations received per article published in the journal over last 2 years.
ntroduction :
The new coronavirus disease 2019 (COVID-19) infection, emerged in Wuhan city, China, in December 2019,
This article report 8 covid 19 infected kidney transplant patient.
Case Reports :
Patient 1:
a 21-year-old female – who had a deceased donor kidney transplant in December 2019 presented on March 30 with fever (39.2°C) ,no other symptoms ,positive covid ,managed by supportive and stop of ant proliferative i.e. MMF.
Patient 2:
a 71-year-old male with hypertensive nephropathy who received a kidney graft in February 2016. He had a history of colon adenocarcinoma in June 2019. His baseline Cr was 240–260 “mol/L. His immunosuppressive regimen included prednisolone 5 mg OD, tacrolimus (trough level was 6.4 ng/mL), and MMF 250 mg BD. He presented with a dry cough with no other symptoms. a chest X-ray revealed a patchy bilateral consolidation. He was tested positive for COVID-19. MMF discontinued and received supportive treatment IV fluid and symptomatic treatment. He was discharged 2 days later with stable kidney functions.
Patient 3:
a 50-year-old male with a history of Wegner’s granulomatosis received a live donor kidney transplant in February 2020. He presented with productive cough and was tested positive for SARS-CoV-2 RNA despite unremarkable clinicalexamination. The chest X-ray was clear, and kidney function tests were stable. His immunosuppressive drugs were prednisolone 5 mg OD, tacrolimus (trough level was 13.4 ng/mL), and MMF 500 mg BD. The management included discontinuation of MMF, reduction of tacrolimus dose, and self-isolation at home. He was advised to drink plenty of fluids and report to the unit any new symptoms.
Patient 4:
a 63-year-old male with a history of IgA nephropathy with a deceased donor kidney transplant in December 2005. He presented with fever (38.8°C) and acute kidney injury (AKI; Cr 297 “mol/L, baseline 110 “mol/L). The chest X-ray showed patchy bilateral consolidation, and SARS-CoV-2 RNA was positive. Blood culture was positive for staphylococcus aureus. Serum (CRP) was 175 mg/L, and serum ferritin
was 929 “g/L. His immunosuppressive regimen was prednisolone 5 mg OD, tacrolimus (trough level was 2.7 ng/mL), and MMF 500 mg BD. The patient was admitted and received IV broad-spectrum antibiotics and paracetamol. We stopped MMF and increased thetacrolimus dose. Kidney function tests improved (serum Cr decreased to 113 “mol/L). The patient recovered and discharged home after 7 days.
Patient 5:
A 47-year-old female with bronchial asthma received a deceased donor kidney transplant in December 2019. She was maintained on prednisolone 5 mg OD, tacrolimus with levels between
5 and 7 ng/mL, and MMF 250 mg BD. She presented on April 6 with dry cough and shortness of breath but no fever. Chest X-ray revealed bilateral middle and lower zone consolidation. COVID-19 were positive. Kidney function tests showed AKI (Cr 302 “mol/L and baseline 162
“mol/L), and mild proteinuria (urine protein/Cr ratio 127 mg/
mmol and baseline <30 mg/mmol). Microbiology workup showed positive urine culture for E. coli . Serum CRP on admission was 344 mg/L and ferritin 2684 “g/L, with leukocytosis (white cell counts 25.8 × 109/L) and lymphopenia (lymphocyte count 0.7 × 109/L). Serum interleukin-6 was 22.2 pg/mL
(n = 0–7 pg/mL). She was tachypnoeic with a respiratory rate of 36 breaths/min, and the peripheral oxygen saturation was 80%, therefore admitted to the intensive therapy unit (ITU) for non-invasive
ventilation . she required intubation and invasive ventilation. Bronchoalveolar lavage showed moderate growth of aspergillus. She received broad-spectrum antibiotics and antifungals. MMF was discontinued. Her kidney functions deteriorated, and she became anuric; therefore, continuous veno-venous haemodiafiltration (CVVH) was commenced. After 14 days, she was weaned off mechanical ventilation and transferred from the ITU to the medical ward. Her kidney functions improved (estimated glomerular filtration rate was 17 mL/min per 1.73 m2, urine protein/ Cr ratio, 40 mg/
Patient 6:
A 71-year-old female with type II diabetes, received deceased donor kidney transplantation in November 2015. Her immunosuppressive therapy included prednisolone, tacrolimus,and MMF. She presented on April 2 with fever (38.5°C) and no other complaint. Chest X-ray showed bilateral peripheral mid and lower zone consolidation. positive for COVID-19 RNA. Kidney function tests showed no change from baseline, and microbiological tests were negative. Serum CRP was 19 mg/L, while serum ferritin was 1,835 “g/L. She was admitted to the medical ward for adequate hydration and symptomatic treatment. MMF was discontinued and discharged after 4 days with fullrecovery.
Patient 7:
A 40-year-old female with hypertension received deceased donor kidney transplantation in June 2017. She is maintained on prednisolone, tacrolimus, and MMF. On April 10, she presented with fever (39°C) and dry cough . COVID-19 RNA were positive. Kidney function tests were stable and microbiological analyses were negative. She was admitted to the medical ward, where MMFwas discontinued, Paracetamol and IV fluids were administered and discharged after 4 days with full recovery.
Patient 8:
A 38-year-old male with a failing kidney transplant from June 2013 presented with productive cough (of clear sputum) and shortness of breath for 2 days. He was maintained on prednisolone 5 mg OD, tacrolimus, and azathioprine. On admission on March 20, he had tachypnoea and hypoxaemia with oxygen saturation of 89% on room air, which improved to >96% on 4 L/min oxygen through a nasal cannula. Positive for COVID-19 RNA. Kidney function tests remained unchanged (Cr 648 “mol/L) despite the high baseline Cr. Chest X-ray revealed bilateral infiltrates. Management included discontinuationof azathioprine, reduction of tacrolimus dose, and increase ofprednisolone dose to 15 mg OD. He did not require any dialysis. Oxygen saturation recovered to >95% on room air, and the patient was discharged after 2 days.
Discussion
The most common initial symptoms were fever (5 patients) and cough
(5 patients). All 8 patients were receiving prednisone and
tacrolimus, 7 patients were receiving mycophenolate
mofetil, and 1 patient was receiving azathioprine. Two
patients had AKI (cases 4 & 5); 1 of them required continuous veno-venous hemofiltration (case 5). Blood results showed that all patients had lymphopenia and high CRP.
chest X-ray was performed in 7 patients, which was clear
in 2 of them,
One managed as an outpatient
and advised to self-isolate at home, with the remaining 7
requiring hospital admission.
One patient required ITU
admission, where she needed mechanical ventilation
(case 5). Bronchoalveolar lavage of this patient confirmed
aspergillosis for which she is receiving antifungal treatment
(another contributing factor for deterioration). Another
patient required ward-based oxygen therapy (case
8). The other 6 patients received supportive therapy on
the renal ward. Antiproliferative immunosuppressive drugs were discontinued for all patients.
Transplant patients are at a high risk of infection due to multiple risk factors, including :
1- immunosuppression,
2- underlying CKD,
3- associated comorbidities, especially hypertension and diabetes .
Many studies reported that hypertensive and diabetic patients have a double-fold risk of infection, while COPD patients have a 5-fold risk.
One study report 1% of COVID-19 patients had a history of malignancy, which was higher than the prevalence of cancer in the overall Chinese population (0.29%).
In our case series, the most frequent presentation was
fever (5 patients) and cough (5 patients).
Two of our patients had AKI , recent studies showed a higher frequency of renal abnormalities.
Cheng et al. reported that among 710 patients, 44% had proteinuria, 26.7% had haematuria, and 14.1% had high serum Cr.
The pathophysiology of renal involvement is still unclear,
1- cytokine storm syndrome.
2- direct renal injury by the virus.
In cases of AKI associated with SARS and MERS, continuous renal replacement therapy showed promising results . It was assumed that high-volume hemofiltration could remove inflammatory cytokines (tumour necrosis factor, IL-6, and IL-1) involved in the pathogenesis of renal injury .
Therefore, continuous renal replacement therapy may play a role in the management of AKI in COVID-19 patients.
Two more reports demonstrated that patients who had a significantly low lymphocyte/white blood cell ratio both on admission and during hospitalization had fatal outcomes
Management :
1- 6 of our patients had their antiproliferative drugs stopped, and they received supportive treatment; 1 patient needed oxygen therapy, and 1 required mechanical ventilation.
2- None of our patients received specific antiviral drugs.
3- When managing immunosuppression in kidney transplant recipients, the following should be considered :
a. the age,
b. the severity of infection,
c. the post-transplant duration,
d. associated comorbidity,
e. Tissue mismatch.
f. any episodes of rejection .
4- in mild infections, the usual practice is to continue or reduce the dose of immunosuppressive drugs.
5- The author suggest discontinuation of the antiproliferative drugs (azathioprine and mycophenolate mofetil) while monitoring the patients closely. Although the author prefer to stop the anti -proliferative drugs first in cases of severe infection.
6- In severe cases requiring mechanical ventilation, we can argue about ceasing calcineurin inhibitors while maintaining corticosteroid therapy.
7- convalescent plasma – derived from the blood of recovered patients – was used as a treatment option but its efficacy was questionable.
8- combination of lopinavir and ritonavir were discouraging.
9- remdesivir – the US Food and Drug Administration has authorized the use of remdesivir as a treatment option for hospitalized COVID-19 patients.
Q2- What is the level of evidence provided by this article?
Level of evidence 4 .
Q3- What is meant by the impact factor of a journal?
Impact factor is commonly used to evaluate the relative importance of a journal within its field and to measure the frequency with which the “average article” in a journal has been cited in a particular time period. Journal which publishes more review articles will get highest IFs
This short series demonstrates experience in managing COVID-19 disease in renal transplant patients in the absence of strong evidence.
The most frequently associated comorbidity was hypertension.
The most common presenting features were fever and cough.
The main radiological investigation was a portable chest X-ray.
Other common features included lymphopenia, high C-reactive protein, and a very high ferritin level.
Management included supportive treatment (intravenous fluid therapy, monitoring renal function, and symptomatic treatment with or without ward-based oxygen therapy depending on oxygen saturation) and discontinuation of the antiproliferative immunosuppressive drugs.
Supportive treatment could be sufficient for the management or to be tried first.
Introduction
In the UK, mortality cases exceeded 30,000 so far. There is a common belief among transplant clinicians that kidney transplant recipients have a high risk of infection due to long-term immunosuppression and associated comorbidities. Data, clinical picture, and outcomes of COVID-19 in kidney transplant recipients are scarce.
Discussion
Many studies showed that COVID-19 infection is associated with high CRP. Guan et al. reported that 60.7% of patients had an elevated CRP, while severe cases had a higher level compared to the non-severe ones (81.5 vs. 56.4% for CRP).
Other reports noticed that high CRP could be linked to unfavourable outcomes, such as ARDS development ,myocardial damage ,and death .
Serum ferritin was measured in only 3 of our patients, and the level was very high. Many reports suggested that higher serum ferritin is associated with ARDS development and death .Ferritin is an acute-phase protein, but we are not sure about the sensitivity and specificity concerning the outcome.
IL-6 is considered a novel biomarker for COVID-19 diagnosis.
Other studies suggested that increased IL-6 levels can be associated with an increased risk of mortality.
there is no clear evidence to support the role of IL-6 blocker (tocilizumab) in treatment of COVID-19 in both transplant and non-transplant population.
The British Society of Thoracic Imaging (BSTI) issued guidelines which state that there is no recommended use of CT unless there is high suspicion with normal or uncertain appearance of CXR in a seriously ill patient .
It is also essential for clinicians of all specialities to be familiar with the radiological findings of COVID-19 on chest X-ray.
Generally speaking, in mild infections, the usual practice is to continue or reduce the dose of immunosuppressive drugs.
we suggest discontinuation of the antiproliferative drugs (azathioprine and mycophenolate mofetil) while monitoring the patients closely.
Remdesivir was used as a compassionate treatment that showed promising results .
Besides, the Adaptive COVID-19 Treatment Trial (NCT04280705) proved that remdesivir-treated patients had 31% faster time to recovery when compared to control .
Based on the previous results, the US Food and Drug Administration has authorized the use of remdesivir as a treatment option for hospitalized COVID-19 patients .
Conclusion
In the above report, the presentations of COVID-19 infected renal transplant patients were not different from the general population where fever and cough were the most frequent symptoms. We believe that our transplant patients did not behave differently from the general population as far as COVID-19 infection is concerned. Because of the small sample size, we could not evaluate the effect of immunosuppression on the course of the disease, but at least it is not a detrimental effect. Based on our experience, supportive treatment could be sufficient or at least to be tried first. It is worth mentioning that the clinical examination supported by simple bedside measures such as oxygen saturation and portable CXR rather than CT scan could be enough and limit the spread of infection. We also found that short hospital stay with self-isolation on discharge reduces the burden on the health service and protect the staff and the public. Since remdisivir was approved for the treatment of COVID-19 and its interaction with CNI is yet unknown, we recommend treatment with remdisivir in a hospital setting where CNI drug level monitoring is available.
Reports of 8 cases of kidney transplant recipients infected with COVID-19 (median age = 48.5 years; range = 21–71 years), including 4 males and 4 females. The most frequently associated comorbidity was hypertension.
The most common presenting features were fever and cough. The main radiological investigation was a portable chest X-ray. Other common features included lymphopenia, high C-reactive protei and a very high ferritin level. Introduction :
The new coronavirus disease 2019 (COVID-19) infection, emerged in Wuhan city, China, in December 2019, Data, clinical picture, and outcomes of COVID-19 in kidney transplant recipients are scarce Therefore, we report 8 cases of kidney transplant recipients infected with COVID-19.
Case Reports :
Patient 1:
a 21-year-old female – who had a deceased donor kidney transplant in December 2019 presented on March 30 with fever (39.2°C) ,no other symptoms ,positive covid ,managed by supportive and stop of ant proliferative i.e. MMF.
patient 2:
a 71-year-old male with hypertensive nephropathy who received a kidney graft in February 2016. He had a history of colon adenocarcinoma in June 2019. His baseline Cr was 240–260 μmol/L. test positive for covid-19 ,treated with stop of MMF and supportive treatment.
patient 3:
a 50-year-old male with a history of Wegner’s granulomatosis received a live donor kidney transplant in February 2020. He presented on April 3 with productive cough and was tested positive for SARS-CoV-2 RNA despite unremarkable clinical examination.
the management included discontinuation of MMF, reduction of tacrolimus dose, and self-isolation at home.
Patient 4:
a 63-year-old male with a history of IgA nephropathy with a deceased donor kidney transplant in December 2005.
presented on March 20 with fever (38.8°C) and acute kidney injury (AKI; Cr 297 μmol/L, baseline 110 μmol/L). The chest X-ray showed patchy bilateral consolidation, and SARS-CoV-2 RNA was positive. Blood culture was positive for staphylococcus aureus.
stopped MMF and increased the tacrolimus dose. K
idney function tests improved (serum Cr decreased to 113 μmol/L). patient discharged stable.
Patient 5:
A 47-year-old female with bronchial asthma received a deceased donor kidney transplant in December 2019. She presented with dry cough and shortness of breath but no fever. Chest X-ray revealed bilateral middle and lower zone consolidation. Nose and throat viral swabs for COVID-19 were positive. Kidney function tests showed AKI (Cr 302 μmol/L and baseline 162 μmol/L), and mild proteinuria (urine protein/Cr ratio 127.
She was tachypnoeic with a respiratory rate of 36 breaths/min, and the peripheral oxygen saturation was 80%, therefore admitted to the intensive therapy unit (ITU) for non-invasive ventilation . Her respiratory functions got worse, and she required intubation and invasive ventilation.
Bronchoalveolar lavage showed moderate growth of aspergillus. She received broad-spectrum antibiotics and antifungals. No specific antiviral drugs were given.
MMF was discontinued. Her kidney functions deteriorated, and she became anuric; therefore, CVVH was commenced. After 14 days, she was weaned off mechanical ventilation and transferred from the ITU to the medical ward. Her kidney function improved and discharged home.
Patient 6:
A 71-year-old female with type II diabetes, received deceased donor kidney transplantation . . She presented with fever (38.5°C) and no other complaint. Chest X-ray showed bilateral peripheral mid and lower zone consolidation. Nasal and throat swabs were positive for COVID-19 RNA.
Kidney function tests showed no change from baseline, and microbiological tests were negative. She was admitted to the medical ward for adequate hydration and symptomatic treatment. MMF was discontinued and discharged after 4 days with full recovery.
Patient 7:
A 40-year-old female with hypertension received deceased donor kidney transplantation . On April 10, she presented with fever (39°C) and dry cough with no other symptoms. Nose and throat swabs for COVID-19 RNA were positive. Kidney function tests were stable and microbiological analyses were negative. She was admitted to the medical ward, where MMF was discontinued, Paracetamol and IV fluids. good recovery and discharged home.
Patient 8
: A 38-year-old male with a failing kidney transplant from June 2013 presented with productive cough shortness of breath for 2 days.test positive and she was desaturated.
Management included discontinuation of azathioprine, reduction of tacrolimus dose, and increase of prednisolone dose to 15 mg OD. He did not require any dialysis. Oxygen saturation recovered to >95% on room air, and the patient was discharged after 2 days.
Discussion:
Fever was reported to be the most common symptom followed by cough.
renal abnormalities. Cheng et al. reported that among 710 patients, 44% had proteinuria, 26.7% had haematuria, and 14.1% had high serum Cr.
Therefore, continuous renal replacement therapy may play a role in the management of AKI in COVID-19 patient.
Al Many reports suggested that higher serum ferritin is associated with ARDS development [and death .
generally speaking, in mild infections, the usual practice is to continue or reduce the dose of immunosuppressive drugs and stop in severe infection.
Conclusion:
In the above report, the presentations of COVID-19 infected renal transplant patients were not different from the general population where fever and cough were the most frequent symptoms.
supportive treatment could be sufficient or at least to be tried first.
It is worth mentioning that the clinical examination supported by simple bedside measures such as oxygen saturation and portable CXR rather than CT scan .
Since remdisivir was approved for the treatment of COVID-19 and its interaction with CNI is yet unknown, we recommend treatment with remdisivir in a hospital setting where CNI drug level monitoring is available.
article summaries 8 cases of post transplant covid disease
cough and fever is common presentation
supportive therapy is required
Hypertension is commonest comorbidity
renal involvement is seen in 2 cases , but it is reported to be low in covid cases
stopping antiproliferative drugs is advised
CXR is common test to monitor lung image
general behaviour is same like non transplant patients
level 1 evidence
impact factor
It reflect how commonly the articles are cited after its publication in that jounal
number of citation divided by total number of publication of previous 2 years
high the impact factor , better is the reputation or acceptance of that journal
You have noticed that I published this article before the publication of the results of the RECOVERY trial. Do you think I would have treated these patients differently?You have noticed that I published this article before the publication of the results of the RECOVERY trial. Do you think I would have treated these patients differently?
short answer is NO
most cases are early in the phase and can be managed on supportive care
Introduction: New coronavirus disease 2019 (COVID-19) infection, which is structurally similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV), affected people worldwide but the data regarding this infection among the transplant recipients is lacking. The article deals with 8 kidney transplant recipients infected with COVID-19.
Case reports: Patient 1: 21-year-old female, 4 months post-transplant, presented with only fever without any respiratory involvement. Throat/ nasal swab for COVID-19 was positive. She was admitted and given supportive treatment, MMF stopped, and discharged after 2 days. Patient 2: 71-year-old male, 4 years post-transplant, history of colon adenocarcinoma 6 months back and with chronic graft dysfunction, presented with dry cough and x ray chest showed bilateral lung involvement. Throat/ nasal swab for COVID-19 was positive. He was admitted and given supportive treatment, MMF stopped, and discharged after 2 days. Patient 3: 50-year-old male, 2 months post-transplant, history of granulomatous polyangitis, presented with productive cough and a clear x ray chest. COVID-19 test was positive. MMF was stopped. He was advised home isolation and supportive treatment. Patient 4: 63-year-old male, 15 years post-transplant, history of IgA nephropathy, presented with fever and elevated serum creatinine and x ray chest showed bilateral lung involvement. Test for COVID-19 was positive. Blood culture grew staphylococcus aureus, tacrolimus trough levels were low. He was admitted and given supportive treatment with intravenous antibiotics. MMF was stopped while tacrolimus dose was increased, and he was discharged after 7 days. Patient 5: 47-year-old female, 5 months post-transplant, history of bronchial asthma presented with dry cough with shortness of breath and x ray chest showed bilateral lung involvement. Throat/ nasal swab for COVID-19 was positive. Serum creatinine, CRP, IL-2, and ferritin were elevated with urine culture growing E.coli. She was admitted in ICU and given supportive treatment, MMF stopped, and required non-invasive ventilation due to respiratory discomfort, but was intubated in view of worsening respiratory functions. Bronchoalveolar lavage revealed aspergillus. CVVH required in view of worsening renal function. Patient improved after 2 weeks, extubated and shifted to the medical ward from where she was discharged after 1 week. Patient 6: 71-year-old female, 5 years post-transplant, history of diabetes mellitus, presented with fever and x ray chest showed bilateral lung involvement. Throat/ nasal swab for COVID-19 was positive. She was admitted and given supportive treatment, MMF stopped, and discharged after 4 days. Patient 7: 40-year-old female, 3 years post-transplant, history of hypertension, presented with fever and dry cough. Throat/ nasal swab for COVID-19 was positive. She was admitted and given supportive treatment, MMF stopped, and discharged after 4 days. Patient 8: 38-year-old male, 7 years post-transplant, history of chronic graft dysfunction, presented with productive cough and dyspnea for 2 days. Oxygen saturation was low on room air and x ray chest showed bilateral lung involvement. Throat/ nasal swab for COVID-19 was positive. He was admitted and given supportive treatment including oxygen support, tacrolimus dose reduced, azathioprine stopped, prednisolone dose increased, and discharged after 2 days. Discussion: Transplant recipients have increased risk of infection due to underlying CKD, immunosuppression, and presence of co-morbidities like diabetes and hypertension (2-fold risk), and COPD (3-fold risk). The median age of the patients was 48.5 years, with 3 of the patients presenting within 3 months post-transplant.
Most common initial symptoms were fever and cough. 25% of the patients developed acute kidney injury (AKI), with one requiring renal replacement therapy. Renal involvement in COVID-19 is thought to be due to either cytokine storm syndrome, or due to direct viral renal injury. High volume hemofiltration could help by removing inflammatory cytokines.
All patients had lymphopenia and elevated CRP. Lymphopenia has been linked with development of acute respiratory distress syndrome (ARDS)while low lymphocyte/ white blood cell count ratio is associated with increased mortality. Elevated CRP and ferritin have been shown to be associated with ARDS, myocardial damage, and death. Elevated IL-6 has also been shown to be associated with increased mortality.
75% had chest x ray findings. So chest x ray should be the initial imaging of choice with CT reserved for seriously ill patients with uncertain x ray findings. One patient required ward-based oxygen therapy while another required intubation and mechanical ventilation. In mild infections, immunosuppressive drug dose, especially antiproliferative agents can be continued or reduced, while in severe cases calcineurin inhibitors would require cessation. The treatment should be individualized as per the clinical picture of the patient.
Convalescent plasma use as a treatment option is under investigation while remdesivir use has shown promising results with faster recovery in hospitalized patients. Conclusion: COVID-19 presentation in kidney transplant recipients is similar to general population, with fever and cough being the commonest symptoms, and majority of the patients require supportive treatment alone for recovery. Short hospital stay and self-isolation on discharge with remdesivir use in hospitalized patients is advised.
2. What is the level of evidence provided by this article? Level of evidence: Level 4: Case series
3. What is meant by the impact factor of a journal?
Impact factor of a journal implies the average number of citations received per article published in the journal over last 2 years.
☆ COVID-19 has structure similar to (SARS-CoV) and (MERS-CoV)
☆ kidney transplant recipients have a high risk of infection
● A report 8 cases of kidney transplant recipients infected with COVID-19
Case Reports
● Patient 1:
☆ A 21-year-old female
☆ Recieved deceased RTx
☆ presented after 3 m with fever, unwell, with no respiratory symptoms.
☆ Clinical examination was unremarkable
☆ Chest X-ray was clear.
☆ Urine and blood cultures were negative. ☆ A nasal and throat swab for COVID-19 was positive.
☆ She is hypertensive
☆ She discharged after 2 days with full recovery and stable kidney functions.
● Patient 2:
☆ a 71-year-old male
☆ Received a kidney graft
☆ His IS regimen is pred, tac, MMF
☆ He was on CCBs and PPi .
☆ He presented with only a dry cough with stable vital signs.
☆ a chest X-ray revealed a patchy bilateral consolidation.
☆ A nasal and throat swab for COVID-19 was positive.
☆ He received supportive treatment IV fluid and symptomatic treatment.
☆ He was discharged 2 days later with stable kidney functions.
● Patient 3:
☆ a 50-year-old male
☆ A history of Wegner’s granulomatosis
☆ He received a live donor kidney
☆ He presented with productive cough
☆ He was positive for SARS-CoV-2 RNA
☆ clinical examination was negative
☆ The chest X-ray was clear
☆ kidney function tests were stable.
☆ His IS drugs were pred, tac, MMF
☆ MMF was discontinuated, tacrolimus had reduced, and self-isolation at home.
● Patient 4:
☆ a 63-year-old male
☆ Recieved a deceased RTx
☆ He presented with fever and AKI
☆ Chest X-ray showed patchy bilateral consolidation
☆ SARS-CoV-2 RNA was positive.
☆ His IS regimen was pred, tac, MMF
☆ MMF stopped and tac increased
☆ Kidney function tests improved
● Patient 5:
☆ A 47-year-old female
☆ Received a deceased RTx
☆ Her IS regimen was pred, tac, MMF
☆ She presented with dry cough and shortness of breath but no fever.
☆ Chest X-ray revealed bilateral middle and lower zone consolidation.
☆ Nose and throat viral swabs for COVID-19 were positive.
☆ AKI, mild proteinuria and positive urine culture for E. coli and negative blood culture.
☆ He admitted to ICU due to decreased
O2 sat %
☆ She received broad-spectrum antibiotics and antifungals.
☆ No specific antiviral drugs were given.
☆ MMF was discontinued.
☆ Her kidney functions deteriorated, and she began CVVH
☆ After 14 days, she was weaned off mechanical ventilation
☆ Her kidney functions improved
● Patient 6:
☆ A 71-year-old female
☆ Received deceased RTx
☆ Her IS therapy was pred, tac, MMF.
☆ She presented with only fever
☆ Chest X-ray showed bilateral peripheral mid and lower zone consolidation.
☆ Nasal and throat swabs were positive for COVID-19 RNA.
☆ Kidney function tests were stable
☆ MMF was discontinued
● Patient 7:
☆ A 40-year-old female
☆ She received deceased RTx
☆ Her IS therapy was pred, tac, MMF.
☆ She presented with fever and dry cough
☆ Nose and throat swabs for COVID-19 RNA were positive.
☆ Kidney function tests were stable
☆ MMF was discontinued
☆ He discharged after 4 d with full recover.
● Patient 8:
☆ A 38-year-old male
☆ with a failing kidney transplant
☆ presented with productive cough and shortness of breath
☆ He was on pred, tac, and AZA
☆ He had tachypnoea and hypoxaemia
☆ Nasal and throat swabs were positive for COVID-19 RNA.
Kidney function tests were stable
☆ Chest X-ray revealed bilateral infiltrates.
☆ Management included discontinuation of aza, reduction of tac, and increase of
pred, He did not require any dialysis.
☆ Oxygen saturation recovered
Discussion
● Median age = 48.5, range = 21–71 years
● 4 males and 4 females.
● 3 patients had RTx within the last 3 m and the rest were for more than a year
● The most features were fever and cough
● IS therapy was pred,tac, 7 (MMF),1(AZA)
● 2 had AKI and 1 required CVVH
● all pts had lymphopenia and high CRP.
● 3 pts had elevated serum ferritin
● The most comorbidity was hypertension
● Chest X-ray was clear in 2 pts, and viral pneumonia in the rest
● 1 patient was managed as an outpatient
● 7 required hospital admission
● 1 referred to the intensive therapy unit.
● Transplant patients are at a high risk of infection due to multiple risk factors, including immunosuppression, underlying CKD, and associated comorbidities, especially hypertension and diabetes
● Management included supportive treatment (intravenous fluid therapy, monitoring renal function, and symptomatic treatment with or without
ward-based oxygen therapy depending on oxygen saturation) and discontinuation of the antiproliferative immunosuppressive
● Theories suggest a cytokine storm syndrome or direct renal injury by the virus are the pathophysiology of renal involvement
● CRRT can remove inflammatory cytokines involved in the pathogenesis of renal injury and may play a role in the management of AKI in COVID-19 patients.
● High CRP and ferritin could be linked to unfavourable outcomes, such as ARDS , myocardial damage and death
● Seven patients recovered and One patient required intensive care treatment and mechanical ventilation.
● None of our patients received specific antiviral drugs.
● limitations :
☆ small sample size
☆ lacked control groups
● Treatment should be individualized based on the careful assessment of each patient.
● Currently, the US FDA investigates the efficacy of convalescent plasma as a treatment option for patients with severe COVID-19 infection
● Reports suggested that remdesivir can be effective against MERS-CoV and SARS-CoV infections
Conclusion
☆ Renal transplant patients were not different from the general population regarding to symptoms and behavior
☆ Supportive treatment could be sufficient or at least to be tried first.
☆ Short hospital stay with self-isolation
on discharge reduces the burden on the health service and protect the staff and the public.
● Level : 4
● The impact factor of the journal :
☆ Used to evaluate the relative importance of a journal within its field
☆ Measure the frequency with which the “average article” in a journal has been cited in a particular time period.
☆ Journal which publishes more review articles will get highest IFs
☆ In general, the impact factor of 10 or higher is considered remarkable, while 3 is good, and the average score is less than 1.
☆ It is calculated by dividing the number of citations in the JCR year by the total number of articles published in the two previous years
● As For recovery trail solid organ transplant recipients were not included
● RECOVERY trail reported that Baricitinib Dexamethasone, and Tocilizumab reduce deaths so dexamethazon can be used in these patients , as for Tocilizumab and Baricitinib data is sparse
● Recovery trail reported that Tocilizumab reduces deaths and shortens the time taken for patients to be successfully discharged from hospital, and reduces the need for a mechanical ventilator in patients hospitalised with COVID-19
but in SOT patients
A dministration of tocilizumab for treatment of severe COVID-19 among SOT recipients appeared to be safe but was not associated with reduced mortality and the requirement for mechanical ventilation but it was associated with a shorter hospital stay.
● RECOVERY trial reported that baricitinib reduces the risk of death when given to hospitalised patients with severe COVID-19.
● But in SOTR , NIH still recommends use of baricitinib for patients with severe or critical COVID-19 disease with rapid progression and advises that SOTR who receive baricitinib should be monitored closely for secondary infections
● So I think that is nothing could added to patients in this series cases especially the most of them weren’t severe cases
▪︎Amani H Yamani et al. Immun Inflamm Dis. 2022 Mar .Early use of tocilizumab in solid organ transplant recipients with COVID-19: A retrospective cohort study in Saudi Arabia
▪︎Am J Transplant ،2020 Nov; 20(11): 3198–3205. Tocilizumab for severe COVID-19 in solid organ transplant recipients: a matched cohort study
▪︎Bodro M, Cofan F, Ríos J, Herrera S, Linares L, Marcos MÁ, Moreno A, Diekmann F. Use of anti-cytokine therapy in kidney transplant recipients with COVID-19. J Clin Med. 2021;10(1551). [PMC free article] [PubMed]
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
This short series demonstrates experience in managing COVID-19 disease in renal transplant patients in the absence of strong evidence. 8 cases of kidney transplant recipients infected with COVID-19 were reported. There is a common belief among transplant clinicians that kidney transplant recipients have a high risk of infection due to long-term immunosuppression and associated comorbidities.
Management- increased the dose of tacrolimus and MMF was stopped with improvement in renal function, and he was discharged after seven days.
Patient 5
47 year female with bronchial asthma had deceased donor transplantation.
Symptoms- Dry cough and SOB but without fever
X-rays showed consolidations.
Labs- Urine c/s positive with e coli acute kidney injury. Elevated CRP and IL6. BAL showed aspergillosis.
Immunosuppression- Tacrolimus (trough 5-7 + MMF 500mg/day + Prednisone 5mg. Management -She needed ICU admission, intubation, CVVH. MMF was suspended. She received antifungal treatment for aspergillosis. She extubated her kidney function partially improved to Gfr17ml/min not requiring CVVH and discharged in 21 days.
Patient 6
71 years female with T2 DM had deceased donor transplantation.
Symptoms- fever.
X-rays consolidation.
Labs-There was no change in renal function.
Immunosuppression- tacrolimus + MMF + prednisone
Management- MMF was suspended, hospital admission, discharge after four days.
Patient 7
40-year female with HTN deceased donor.
Symptoms fever and dry cough.
Immunosuppression- Tacrolimus + MMF + Prednisone.
Management- MMF discontinued and discharged after four days.
Patient 8
38 year male with failing transplant kidney.
Symptoms- Productive cough and fever.
X ray showed infiltrates.
Immunosuppression-Tacrolimus + Azathioprine and prednisone.
Management- Discontinued Azathioprine, reduce Tacrolimus dose, Increased prednisolone, Needed oxygenation, not needed HD, discharged in 2 days
Antiproliferative immunosuppressive drugs were discontinued for all patients.
In this case series, the most frequent presentation was fever (5) and cough (5)
All patients had lymphopenia and a high CRP level.
5/8 had bilateral patchy consolidation.
Conclusion
Despite the small number of cases, discontinuing antiproliferative drugs is highly recommended. Maintaining corticosteroid therapy is recommended and treatment with remdesivir in a hospital setting where CNI drug level monitoring is available is recommended.
What is the level of evidence provided by this article? Level 4 case series
What is meant by the impact factor of a journal?
Impact factor is commonly used to evaluate the relative importance of a journal within its field.
Impact Factor measures the frequency with which the “average article” in a journal has been cited in a particular time period. The impact factor of a journal is calculated by dividing the number of current year citations to the source items published in that journal during the previous two years.
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence Introduction
· By April 26, 2020, infections related to COVID-19 were responsible for 203,818 reported deaths worldwide.
· Transplant clinicians believe that kidney transplant recipients have a high risk of infection because they are immunocompromised. Case Reports Patient 1: a 21-year-old female – who had a deceased donor kidney transplant in December 2019. She is hypertensive on calcium channel and β-blockers. She was on prednisone, tacrolimus, and MMF. Admitted with COVID-19, given IV fluids and paracetamol, MMF was stopped and discharged after 2 days with full recovery and stable kidney functions. Patient 2: a 71-year-old male with hypertensive nephropathy who received a kidney graft in February 2016. He had a history of colon adenocarcinoma in June 2019. He is on prednisolone, tacrolimus, MMF, calcium channel blockers, and PPI. Admitted with COVID-19, MMF was stopped, given supportive treatment, and discharged 2 days later with stable kidney functions. Patient 3: a 50-year-old male with a history of Wegner’s granulomatosis received a live donor kidney transplant in February 2020, presented with a productive cough, and had positive for SARS-CoV-2 RNA, MMF was stopped, tacrolimus dose reduced, and self-isolation at home. Patient 4: a 63-year-old male with a history of IgA nephropathy with a deceased donor kidney transplant in December 2005. He is on CCB, prednisone, tacrolimus, and MMF. Presented with fever, AKI, bilateral patchy consolidation, +SARS-CoV-2 RNA, +Blood culture for staphylococcus aureus, high CRP, and ferritin. Admitted for broad-spectrum antibiotics, reduced tacrolimus dose, and MMF was stopped. Kidney function tests improved and the patient recovered and was discharged home after 7 days. Patient 5: A 47-year-old female with bronchial asthma received a deceased donor kidney transplant in December 2019. On prednisolone, tacrolimus, and MMF. Presented with dry cough and shortness of breath without fever, bilateral consolidation, + COVID-19. Kidney function tests showed AKI, and mild proteinuria, positive urine culture for E. coli and negative blood culture. Very high CRP and ferritin. e admitted to the intensive therapy unit (ITU) for non-invasive ventilation but she deteriorated and required intubation and invasive ventilation. BAL showed aspergillus. MMF stopped, antibiotics and antifungals were given. Patient 6: A 71-year-old female with type II diabetes, received deceased donor kidney transplantation in November 2015. She is on prednisolone, tacrolimus, and MMF. She presented with fever, bilateral peripheral mid and lower zone consolidation, and was positive for COVID-19 RNA. She was admitted for fluid therapy, MMF was stopped, and discharged after 4 days. Patient 7: A 40-year-old female with hypertension received deceased donor kidney transplantation in June 2017. She is on prednisolone, tacrolimus, MMF, amlodipine and PPI. She was admitted with fever and + COVID-19 RNA. MMF was held, Paracetamol and IV fluids were given and discharged after 4 days with full recover. Patient 8: A 38-year-old male with a failing kidney transplant from June 2013 presented with productive cough and shortness of breath for 2 days. He was on prednisolone, tacrolimus, and azathioprine. Admitted with tachypnoea and hypoxemia ( SaO2 89% on RA), which improved to >96% on 4 L/min oxygen through a nasal cannula. + COVID-19 RNA, high creatinine, and bilateral lung infiltrates. Azathioprine was stopped, tacrolimus dose reduced, and prednisolone dose was increased to 15 mg OD. Discussion
· Hypertensive and diabetic patients have a double-fold risk of infection, while COPD patients have a 5-fold risk
· Liang et al. found that 1% of COVID-19 patients had a history of malignancy
· Many studies showed that COVID-19 infection is associated with high CRP, which linked to unfavorable outcomes.
· Some studies suggested that increased IL-6 levels can be associated with an increased risk of mortality.
· There is no clear evidence to support the role of IL-6 blocker (tocilizumab) in the treatment of COVID-19 in both transplant and non-transplant populations.
· portable chest X-ray is recommended to reduce the transmission of infection.
· Discontinuation of antiproliferative drugs in cases of severe infection is recommended.
· In severe cases requiring mechanical ventilation, calcineurin inhibitors should be stopped while maintaining corticosteroid therapy.
· Trial of the combination of lopinavir and ritonavir among SARS-CoV patients was discouraging.
· Drug Administration has authorized the use of remdesivir as a treatment option for hospitalized COVID-19 patients.
Conclusion
· There is no big difference between COVID-19 infected renal transplant patients and general population.
· supportive treatment should be tried first, and to give remdisivir in a hospital setting
The article of Prof Halawa and collaegues have shown outcome of 8 kidney transplant patients who suffered from Covid 19 during the pandemic.
All patients were discharged safely as one patient was managed as outpatient.
One patient needed Mechanical ventilation and dialysis support and luckily recovered and discharged later.
MMF was with held for all patients which is now considered as a standard of care for these patients.
Level of Evidence
Case series—articles written about a series of patients with a specific diagnosis—are also regarded as level 4 evidence.
Impact Factor?
The impact factor (IF) is a measure of the frequency with which the average article in a journal has been cited in a particular year. It is used to measure the importance or rank of a journal by calculating the times its articles are cited. How Impact Factor is Calculated?
The calculation is based on a two-year period and involves dividing the number of times articles were cited by the number of articles that are citable.
Introduction · COVID-19 has close genomic structural similarities to SARS-CoV and MERS-CoV and has caused 203,818 reported deaths worldwide. · 8 cases of kidney transplant recipients infected with COVID-19 were reported due to long-term immunosuppression and comorbidities. Discussion · 8 cases of COVID-19 infection in kidney transplant patients from Sheffield Kidney Institute, UK, with a median age of 48.5 years, median initial symptoms of fever, cough, prednisone, tacrolimus, mycophenolate mofetil, AKI, lymphopenia, high CRP, elevated serum ferritin, elevated IL-6, and a portable chest X-ray. · 8 patients were managed as outpatients and advised to self-isolate at home, with 7 requiring hospital admission and 6 receiving supportive therapy on the renal ward. Antiproliferative immunosuppressive drugs were discontinued. · Transplant patients are at a high risk of infection due to multiple risk factors, including immunosuppression, underlying CKD, and comorbidities, such as hypertension and diabetes. · Liang et al. reported that 1% of COVID-19 patients had a history of malignancy, higher than the overall Chinese population. · Fever was the most common symptom, followed by cough, with 82-87% of patients having fever and 44-65% with cough. · The incidence of AKI in COVID-19 patients is low, but recent studies have shown a higher frequency of renal abnormalities, suggesting a cytokine storm syndrome or direct renal injury by the virus. Continuous renal replacement therapy may play a role in the management of AKI. · Studies have shown that COVID-19 infection is associated with high CRP levels, which can be linked to unfavorable outcomes such as ARDS development, myocardial damage, and death. · Serum ferritin was also found to be high, suggesting that higher serum ferritin is associated with ARDS development and death. · The most important details are that in- creased IL-6 levels can be associated with an increased risk of mortality and that there is no clear evidence to support the role of IL-6 blocker (tocilizumab) in the treatment of COVID-19 in both transplant and non-transplant populations. · CT decontamination may disrupt radiology service, and portable chest X-rays should be considered to reduce transmission of infection. · Clinicians of all specialties should be familiar with the radiological findings of COVID-19 on chest X-rays. · The most important details are that 6 of the patients had their antiproliferative drugs stopped, 1 needed oxygen therapy, 1 required mechanical ventilation, and none of the patients received specific antiviral drugs. The treatment should be individualized based on the individual assessment of each patient.
· The US Food and Drug Administration has authorized the use of remdesivir as a treatment option for patients with severe COVID-19 infection.. Conclusion · The presentations of COVID-19-infected renal transplant patients were similar to the general population, with fever and cough being the most frequent symptoms.
· Supportive treatment, such as bedside measures such as oxygen saturation and portable CXR, and short hospital stay with self-isolation on discharge are recommended to reduce the burden on the health system and protect the public.
What is the level of evidence provided by this article?Case series Level IV
What is meant by the impact factor of a journal?It’s a measure of the relative importance of a journal within its field like the “average article” in a journal has been mentioned on average x number of times during y time period, The journals with the highest IFs are those that publish the most reviews.
Summarize the article:
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
8 cases of kidney transplant recipients(a group who is considered high risk ), presented with different symptoms and were treated with supportive measures in addition to stopping antimetabolites and were recovered and discharged in 2days with stable renal function.
They presented with one of these symptoms
· lethargy and unwell with fever
· dry cough, chest X-ray revealed a patchy bilateral consolidation
· productive cough, advised home isolation
· fever (38.8°C) and AKI, chest X-ray showed patchy bilateral consolidation. Positive blood culture with staph and high CRP and ferritin
· dry cough and shortness of breath, X-ray revealed bilateral middle and lower zone consolidation & AKI with mild proteinuria and urine culture positive for E. coli and negative blood culture. high CRP and ferritin with leukocytosis and lymphopenia. High serum interleukin. tachypnoea with a high respiratory rate and low oxygen saturation (80%), required admission to the intensive therapy unit (ITU) and intubated. BAL shows aspergillus. She required antibiotics anti fungal and dialysis , eventually improved and discharged in 7 days.
· Fever , Chest X-ray showed bilateral peripheral mid and lower zone consolidation. Stable Kidney function tests, high serum ferritin received symptomatic treatment and hydration and discharged in 4 days.
· fever (39°C) and dry cough Kidney function tests were stable improved in 4 days with symptomatic treatment.
· productive cough and breathing difficulty With tachypnoea and hypoxaemia with oxygen saturation of 89% on room air, Kidney function tests were stable .Chest X-ray showed bilateral infiltrates. patient recovered and discharged after 2 days.
It is noticed that the most frequent presentation was fever and cough , while All the patients had lymphopenia and a high CRP. IL-6 is considered a novel biomarker for COVID-19 diagnosis but found to be high in only 1 patient.
A chest X-ray had positive finding with bilateral patchy consolidation in almost all the cases, the auther suggested that portable chest X-ray should be considered to reduce the transmission of infection rather that CT scan. The Italian and British hospitals employ chest X-ray as a first-line triage tool as the results of COVID-19 testing.
Most of the patient were treated symptomatically , their antimetabolites drugs stopped, and they received supportive treatment. They improved , 2 of them had AKI however recovered.
none of our patients received specific antiviral drugs.
Other treatments were investigated such as efficacy of convalescent plasma and use of antivirals
reports suggested that remdesivir (a broad-spectrum antiviral nucleotide prodrug) can be effective against MERS-CoV and SARSCoV infections. Level of evidence :
IV(anecdotal evidence including author independent opinion and review) impact factor:The journal Impact Factor is an index that measures how frequently articles in a journal are cited in other research. This is calculated by dividing the number of citations received by articles published in that journal over the previous two years by the total number of articles published in that journal over the previous two years.
Summary: Introduction: Covid-19 infection, emerged in Wuhan, China, in December 2019, shares genomic structural similarities with the severe acute respiratory syndrome coronavirus (SARS-CoV). 30,000 UK deaths have occurred due to Covid-19.
It is believed that kidney transplant recipients have a high infection risk due to long-term immunosuppression and comorbidities. Covid-19 is associated with diffuse lung involvement, respiratory failure and increased mortality, and the data available in patients receiving kidney transplant is limited. This study is demonstrate 8 kidney transplant recipients who developed covid-19 post kidney transplantation. Patients profile:
Patients presents initially with fever and cough
6 patients had comorbidities, most common was hypertension
All the patients had lymphopenia and elevated CRP
3 patients had elevated serum ferritin and 1 had high IL-6
6 of 8 patients had abnormalities in CXR
7 of 8 patients were admitted to the hospital, one needed ICU support and one received outpatient management
Treatment:
Supportive care
Stop antimetabolites for all patients
2 patients developed AKI and one received CRRT
Majority of patients discharged earlier (2-7 days), only one 21 days
Conclusion:
Fever and cough were the most frequent symptoms
Supportive treatment could be sufficient for most of the patients
Short hospital stay with self-isolation on discharge reduces the burden on the health service and protect the staff and the public
Treatment with remdisivir in a hospital setting where CNI drug level monitoring is available
Level of evidence:Level 4, case series
Impact factor of a journal: is the frequency by which an article in a journal has been cited in a particular period of time, which in turn reflect the potency and importance of the journal. the impact factor of a journal is calculated by dividing the number of current year citations to the source items published in that journal during the previous two years.
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
Nephron 2021
Case series, level of evidence IV, published 2020 about 8 kidney transplant recipients (4 males and 4 females) who developed covid 19 after transplantation. All maintained on triple therapy include tacrolimus, MMF, prednisolone except one who was on azathioprine instead of MMF.
Clinical presentation:
Patients most commonly presents initially by fever and cough.
6 of 8 patients had abnormalities in CXR
Although patient on immunosuppression medications but the presentation were not that sever and 6 of 8 patients were admitted to the general word one of them was on O2 therapy, 1 patient to the ICU needed MV and one managed as outpatient case.
Management included
Antimetabolite was stopped for all patients plus supportive care.
One received CVVHD.
Conclusion and recommendations
Each patient should be evaluated and categorized to 3 main categories:
Mild case with normal chest Xray and mild clinical symptoms maintaining saturation on room air no modifications or just half dose of MMF maybe needed
Moderate cases with abnormal chest Xray need stoppage of MMF and close monitoring
Sever cases with high oxygen requirement need careful assessment with considering possibility of mixed bacterial, fungal infections and cytokine storm. Impact factor:
measurement of journal citation frequency in a particular year, it calculated dividing number of articles citing by total number of articles.
I. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
Summarise this article.
Introduction
– kidney transplant recipients (KTRs) are thought to have a high risk of infection due to the long-term immunosuppressive therapies and associated comorbidities
Case reports
– 8 cases of KTRs infected with COVID-19 disease
– 4 males, 4 females
– median age 48.5years, range 21-71 years
– 3 patients had been transplanted within the last 3 months, the rest were transplanted for more than 1 year
– hypertension was the most frequently associated comorbidity
– most common presenting features were cough and fever
– portable chest radiograph was the main radiological investigation
– five out of the 8 cases had bilateral patchy consolidation on CXR
– other common features include: high CRP, lymphopenia, high ferritin level
– 1 patient was managed as an outpatient while 7 patients required hospital admission, 1 of them was referred to ICU for further treatment including mechanical ventilation and CVVH, incidentally this patient had aspergillosis on BAL
– 2 developed AKI
– all patients apart from 1 were on tacrolimus, mycophenolate, prednisone – the patient was on tacrolimus, azathioprine and prednisone
– management entailed: – supportive therapy with IVF, monitoring kidney function, symptomatic treatment with oxygen depending on the oxygen saturation, discontinuation of antiproliferative immunosuppressive agents
– 7 patients recovered and were discharged for self-isolation at home
– short hospital stay with home-based self-isolation on discharge reduces the burden on the healthcare system and also protects the staff and the public
Discussion
– risk factors for infection in kidney transplant patients: immunosuppression, associated comorbidities (hypertension, diabetes, COPD, malignancies), underlying CKD
– high CRP could be linked to unfavourable outcomes like ARDS, myocardial injury, death
– high serum ferritin was also associated with ARDS and death so was interleukin 6 (IL-6)
– use of chest CT scan in the COVID-19 era put a significant burden on the radiology department and also made infection control a challenge
– use of portable chest radiographs should therefore be considered to reduce infection transmission
– management involves withdrawal of the antiproliferative drugs and offering supportive treatment
– overall, the management in KTRs depends on the age, severity of infection, associated comorbidities, post-transplant duration, rejection episodes, tissue mismatch
– for mild infections, the common practice is to continue or reduce the dose of immunosuppressive drugs while monitoring the patient closely
– for severe infections, consider stopping the antiproliferative agents
– in severe cases requiring mechanical ventilation, in addition to stopping antiproliferative agents, the CNIs can be withdrawn but usually the corticosteroids are maintained
– individualized treatment is usually advocated for based on thorough assessment of the patient
– there was no evidence to support use of Tocilizumab (IL-6 blocker) in management of COVID 19 in both transplant and non-transplant patients
– the efficacy of convalescent plasma i.e., blood derived from recovered patients was questionable
– the results from the use of lopinavir and ritonavir were also discouraging
– Remdisivir was approved by FDA as viable treatment option for hospitalized COVID-19 patients
Conclusion
– the clinical presentation of COVID-19 in transplant patients is similar to that of the general population where cough and fever were the most frequent symptoms
– supportive treatment plays a critical role in the management of COVID-19 patients
– CT Chest can be avoided by focusing on simple bedside measures like oxygen saturation and portable CXR
– short hospital stay and home-based self-isolation reduces the burden on the health system as well as protects the staff and the public from the infection
– Remdesivir should only be used in a setting where CNI drug level monitoring can be done
Level of evidence provided by this article
Level IV
What is meant by the impact factor of a journal? (1)
– Impact factor (IF) of a journal is a measure of the frequency by which the average article in a journal has been cited in a particular time period i.e., the number of times an average article in a journal is cited during a year
– IF evaluates the relative importance of a journal within its field
Reference
1. Sharma M, Sarin A, Gupta P, Sachdeva S, Desai AV. Journal impact factor: its use, significance and limitations. World journal of nuclear medicine. 2014 May;13(2):146. PubMed PMID: 25191134. Pubmed Central PMCID: PMC4150161. Epub 2014/09/06. eng.
Hydroxychloroquine, Colchicine & Azithromycin have no clinical benefits
Tocilizumab reduces deaths in patients hospitalised with COVID-19. It shortens the time taken for patients to be successfully discharged from hospital, and reduces the need for a mechanical ventilator.
Baricitinib reduces deaths in hospitalised patients; baricitinib reduced deaths by 13%. It also reduced the chance of progressing to invasive mechanical ventilation.
In review of RECOVERY trial results cases 5 and 8 could have received recommended additional medications:
Patient 1 got IV fluids and paracetamol. MMF was discontinued she was discharged after 2 days. Patient 2 received IV fluid and symptomatic treatment. He was discharged 2 days after MMF was discontinued. Patient 3 was advised to drink plenty of fluids. MMF was discontinued; Tacrolimus dose was reduced. Patient 4 was given paracetamol. MMF was discontinued; Tacrolimus dose was increased. Patient 5 needed temporary CVVH and intubation. MMF was discontinued. Recovery may have been faster if Baricitinib and/or Tocilizumab had been used. Patient 6 was admitted for adequate hydration and symptomatic treatment. MMF was discontinued. Patient 7 had MMF discontinued; Paracetamol and IV fluids were administered. Then discharged after 4 days. Patient 8 Management included discontinuation of azathioprine, reduction of tacrolimus dose, and increase of prednisolone dose. Dexamethasone could have been considered instead of prednisolone.
Case Reports
Patient 1: a 21-year-old female – who had a deceased donor kidney transplant in December 2019 presented on March 30 with fever (39.2°C).
The chest X-ray was clear, and kidney function tests were stable
His immunosuppressive drugs were prednisolone 5 mg OD, tacrolimus, and MMF 500 mg BD.
Patient 4: a 63-year-old male with a history of IgA nephropathy with a deceased donor kidney transplant in December 2005
He is hypertensive and maintained on calcium channel blockers.
Patient 5: A 47-year-old female with bronchial asthma received a deceased donor kidney transplant in December 2019
She was maintained on prednisolone 5 mg OD, tacrolimus with levels between 5 and 7 ng/mL, and MMF 250 mg BD.
Patient 6: A 71-year-old female with type II diabetes, received deceased donor kidney transplantation in November 2015
Her immunosuppressive therapy included prednisolone, tacrolimus, and MMF.
Patient 7: A 40-year-old female with hypertension received deceased donor kidney transplantation in June 2017
She is maintained on prednisolone, tacrolimus, and MMF.
Patient Age/sex Tx date Comorbidities Fever Respiratory involvements Renal involvements Baseline immunosuppression
2 71/M Feb 2016 Hypertension and post-Tx malignancy No Dry cough No Pred-Tac-MMF. 5 47/F Dec 2019 Bronchial asthma, aspergillosis No Dry cough + SOB AKI Pred-Tac-MMF.
2 71/M Feb 2016 Hypertension and post-Tx malignancy No Dry cough No Pred-Tac-MMF.
5 47/F Dec 2019 Bronchial asthma, aspergillosis No Dry cough + SOB AKI Pred-Tac-MMF.
COVID-19, coronavirus disease 2019; F, female; M, male; Tx date, date of transplant; post-Tx, post-transplant; DM, diabetes mellitus; SOB, shortness of breath; Pred, prednisolone; Tac, tacrolimus; MMF, mycophenolic acid; Aza, azathioprine Discussion
We present our experience with 8 cases of COVID-19 infection in kidney transplant patients from Sheffield Kidney Institute, UK.
Three patients had kidney transplantation within the last 3 months, and the rest were transplanted for more than a year.
One of our 8 patients was managed as an outpatient and advised to self-isolate at home, with the remaining 7 requiring hospital admission.
One patient required ITU admission, where she needed mechanical ventilation.
Bronchoalveolar lavage of this patient confirmed aspergillosis for which she is receiving antifungal treatment.
The other 6 patients received supportive therapy on the renal ward.
Transplant patients are at a high risk of infection due to multiple risk factors, including immunosuppression, underlying CKD, and associated comorbidities, especial- Findings
Guan et al, reported that 83.2% of infected patients had lymphopania on admission Color version available online
Many studies discussed the outcome of such comorbidities in COVID-19 patients.
These studies reported that hypertensive and diabetic patients have a double-fold risk of infection, while COPD patients have a 5-fold risk.
Liang et al, reported that 1% of COVID-19 patients had a history of malignancy, which was higher than the prevalence of cancer in the overall Chinese population (0.29%).
In cases of AKI associated with SARS and MERS, continuous renal replacement therapy showed promising results .
Many studies showed that COVID-19 infection is associated with high CRP..
The US Food and Drug Administration investigate the efficacy of convalescent plasma as a treatment option for patients with severe COVID-19 infection.
Drug Administration has authorized the use of remdesivir as a treatment option for hospitalized COVID-19 patients. Conclusion
The presentations of COVID-19 infected renal transplant patients were not different from the general treatment where fever and cough were the most frequent symptoms.
We believe that our transplant patients did not behave differently from the general population as far as COVID-19 infection is concerned.
Supportive treatment could be sufficient or at least to be tried first.
It is worth mentioning that the clinical examination supported by simple bedside measures such as oxygen saturation and portable CXR rather than.
We found that short hospital stay with self-isolation on discharge reduces the burden on the health services and protect the staff and the public.
Since remdisivir was approved for the treatment of COVID-19 and its interaction with CNI is yet unknown, we recommend treatment with remdisivir in a hospital setting where CNI drug level monitoring is available Level of evidence 5 impact factor of a journal
An academic journal’s impact factor is a scientometric index that is used to assess how important the journal is compared to others in its field.
The annual mean number of citations of articles published in the previous two years in a particular publication is reflected in the impact factor.
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
This is a case series analysis of eight KTRs with COVID-19 infection.
The common features of COVID-19 in KTRs of these cases were :
1. Fever and cough are the most common presenting feature.
2. Lymophopenia, high C-reactive protein, and a very high ferritin level.
3. HTN is the most common associated co-morbidity.
4. Two patients had AKI, one of them required continuous veno-venous hemofiltration.
The therapeutic strategies for managing these KTRs with COVID-19 infection were as follows:
1. Antiproliferative immunosuppressive drugs were discontinued for all patients.
2. An outpatient management and advised to self-isolate at home(1 patient).
3. Hospital admission and supportive therapy on the renal ward (intravenous fluid therapy, monitoring renal function, and symptomatic treatment with or without ward-based oxygen therapy based on the oxygen saturation)(6 patients).
4. ITU admission and mechanical ventilation(1 patient).
5. Continuous Veno-Venous Hemofiltration-CVVH (1 patient; ITU admission+ mechanical ventilation and CVVH).
Discussion:
1. Early studies reported that the incidence of AKI was low (3–9%).
2. Recent studies(Cheng et al) showed a higher frequency of renal abnormalities among 710 patients:
· 44% had proteinuria.
· 26.7% had haematuria.
· 14.1% had high serum Cr.
3. The pathophysiology of renal involvement is still unclear, but theories suggest:
· A cytokine storm syndrome.
· Direct renal injury by the virus.
4. Diagnosis and laboratory features of COVID-19 infection:
· Low lymphocyte/white blood cell ratio had fatal outcomes.
· High CRP(60.7%) is linked to unfavorable outcome; ARDS, myocardial damage and death.
· Higher serum ferritin is associated with ARDS development and death.
· High IL-6 levels (52% ); a novel biomarker for COVID-19 diagnosis and can be associated with an increased risk of mortality.
· CXR my show patchy consolidation.
· CT when there is high suspicion with normal or uncertain appearance of CXR in a seriously ill patient.
5. Management of COVID-19 infection:
A. Mild infections: the usual practice is to continue or reduce the dose of immunosup- pressive drugs. Discontinuation of the antiproliferative drugs is suggested.
B. Severe infection with requirement to mechanical ventilation: to maintain corticosteroids, hold antiproliferative and to argue about ceasing CNIs.
C. Remdesivir-treated patients had 31% faster time to recovery when compared to control.
D. CRRT may play a role in the management of AKI in COVID-19 patients. It was assumed that high-volume hemofiltration could remove inflammatory cytokines (tumour necrosis factor, IL-6, and IL-1β) involved in the pathogenesis of renal injury.
The level of evidence provided by this article:
This is a case series study with level of evidence grade 5.
The impact factor of a journal:
The Impact factor (IF) or journal impact factor (JIF) is a sciento-metric index calculated by Clarivate that reflects the yearly mean number of citations of articles published in the last two years in a given journal, as indexed by Clarivate’s Web of Science.
Limitations of the JIF
· Some journals increased the impact factor value by reducing the number of scholarly records.
· Extension of the impact factor to the assessment of journal quality or individual authors is inappropriate.
· Extension of the impact factor to cross-discipline journal comparison is also inappropriate.
· Those who choose to use the impact factor as a comparative tool should be aware of the nature and premise of its derivation and also of its inherent flaws and practical limitations.
Introduction: The new coronavirus disease 2019 (COVID-19) infection emerged in Wuhan city, China in December 2019 . By April 26, 2020, 203,818 reported deaths worldwide and mortality cases exceeded 30,000. There is a common belief that kidney transplant recipients have a high risk of infection due to long-term immunosuppression and associated comorbidities.8 cases of kidney transplant recipients infected with COVID-19 were reported .
Case report and discussion :
This report discusses 8 cases of COVID-19 infection in kidney transplant patients from Sheffield Kidney Institute, UK, with median age 48.5 years ,4 males and 4 females . All 8 patients were receiving prednisone and tacrolimus, 7 patients were receiving mycophenolate mofetil, and 1 patient was receiving azathioprine. Six patients had multiple comorbidities (4 had hypertension, 1 had type II DM,1 had bronchial asthma and aspergillosis, and 1 had a history of cancer). In this case series, the most frequent presentation was fever (5 patients) and cough (5 patients). Fever was reported to be the most common symptom followed by cough . Two large studies demonstrated that 82-87% of their patients had a fever, while patients with cough ranged from 44 to 65. Two of our patients had AKI (cases 4 & 5); 1 of them required renal replacement therapy in the form of CVVH (case 5). Early studies reported that the incidence of AKI was low (3-9%) in those with COVID-19 infection, but recent studies showed a higher frequency of renal abnormalities.
Low lymphocyte/white blood cell ratio and high CRP are associated with fatal outcomes, while serum ferritin is associated with ARDS development and death. IL-6 is considered a novel biomarker for COVID-19 diagnosis, but is not routinely measured. The role of IL-6 blocker (tocilizumab) in treatment of COVID-19 in both transplant and non-transplant population was found in 7 patients, five of whom had bilateral patchy consolidation and 2 who had no classical changes.
CT decontamination may disrupt service availability and portable chest X-ray should be considered to reduce transmission. The British Society of Thoracic Imaging (BSTI) issued guidelines which state that CT should not be used unless there is high suspicion of CXR in a seriously ill patient. Managing immunosuppression in kidney transplant recipients should be individualized based on the patient’s age, severity, post-transplant duration, comorbidity, tissue mismatch, and any episodes of rejection.
Conclusion : The presentations of COVID-19-infected renal transplant patients were similar to the general population, with fever and cough being the most frequent symptoms. Supportive treatment should be tried first, and short hospital stays with self-isolation on discharge reduce the burden on the health service and protect the public.
?What is the level of evidence provided by this article
level IV(Case series )
?What is meant by the impact factor of a journal
The impact factor of an academic journal is a scientometric index which is used to evaluate the relative importance of a journal within its field. The impact factor reflects the yearly mean number of citations of articles published in the last two years in a given journal.
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
Summary:
· Cases with COVID 19 infection, were included (most common symptom was fever and cough, with hypotension as comorbidity). All had lymphopenia, high CRP and ferritin levels. Diagnosis was confirmed by nasal/throat swab for COVID 19 RNA. CXR was either normal or showing bilateral infiltration suggestive of viral pneumonia.
· KTR are at higher risk of infection due to IS therapy, CKD condition and other comorbidities as hypertension or DM.
· 2 cases presented with AKI (one case required CVVHF), the mechanism of renal involvement ay be either direct viral invasion or involvement as a part of cytokine storm. So, CVVH may help by removing circulating cytokines as TNF alfa, IL -1 and IL-6.
· Supportive treatment with oxygen, antipyretic (paracetamol) and IV fluid therapy with early discharge to home isolation was better to decrease the burden, cost and infections among health care workers.
· All patients were informed to drink plenty of fluids and to report any new symptoms to the hospital.
· Discontinuation of antiproliferative MMF was done in all hospitalized cases.
· Higher levels of CRP and severe lymphopenia were linked to development of ARDS and worse prognosis.
· Although IL-6 is a new marker for COVID 19 diagnosis, no clear evidence to support its diagnostic or prognostic role (so not done routinely in all cases and also the role of IL-6 blocker (tocilizumab) is not clear.
· CXR should be 1st imaging modality in suspected COVID cases to avoid burden on CT and uncontrollable spread of infection.
· Still, case series research cannot provide clear guidelines for management, but the current article can suggest that:
o In mild cases, reduction or stoppage of antiproliferative (MMF/ AZA).
o In severe /ventilated cases: consider CNI stoppage and keep or even slight increase in steroids dose.
o Individualized therapy according to severity of infection, comorbid condition, time since transplantation all can play a role in management plan.
o Convalescent plasma derived from recovered cases is still questionable if it has value for severe cases.
o None of the included cases received antiviral therapy.
o RCTs showed that combination of lopinavir and ritonavir among SARS-CoV patients has no value (discouraging results).
o While remdesivir-treated patients had 31% faster time to recovery when compared to control, so may be a promising treatment option in hospitalized cases with close monitoring of CNI level.
Level of evidence: case series is level 4
Meaning of journal impact:
· is a term used to evaluate the relative importance of a journal in a particular field of science. It is derived from the frequency of citation of its articles in a particular period of time.
· Journals with much publication of review articles will have higher impact factor.
The RECOVERY trial has found that there are other treatment options that were effective in COVID 19 treatment as: For COVID-19
sotrovimab (a monoclonal antibody treatment against the spike protein)
molnupiravir (an antiviral treatment)
paxlovid (an antiviral treatment)
In addition, use of high dose dexamethasone ( 6mg once daily for 10 days or until discharge in hospitalized patients requiring oxygen (with or without non-invasive ventilation) and for patients on invasive mechanical ventilation or extra-corporeal membranous oxygenation (ECMO). As a consequence, dexamethasone 6 mg once daily is now widely recommended for treatment of such patients.
I think addition of dexa can be used for the case who required MV and CVVHF. Also use of new available drugs is worthy trying in severe cases as case with CVVH.
While in the rest of cases with short hospitalization, I think no added treatment was required.
Tocioizumab has found to increase mortality among KTR .
Dear All You have noticed that I published this article before the publication of the results of the RECOVERY trial. Do you think I would have treated these patients differently?
Thank you Professor Halawa for the question
In the majority of the trials of COVID 19 therapeutic, solid organ transplant recipients were not included. Most of the data comes from retrospective studies where these therapeutic agents were used in SOT recipients.
Tocilizumab has been evaluated in observational studies. In a study by Perez-Saez et al, the SOT recipients who received Tocilizumab had a higher mortality rate of 32.5% which was significantly higher that in the SOT recipients in earlier studies. This was postulated to be due to the higher baseline inflammatory markers in the SOT recipients. In a matched cohort study of 117 SOT recipients, 29 patients received tocilizumab compared to matched controls and no benefit in mortality was found. This study noted an increase in secondary infections in the tocilizumab group.
The NIH and the American Society for Transplantation recommend the use of baricitinib in SOT recipients with severe/critical COVID 19 disease with rapid progression
Stopping the anti-metabolite and supportive care still remain the gold standard for treatment of COVID 19 in SOT recipients
Baricitinib could be used in critical/severe COVID 19 disease
In This case series, there was only one patient who required mechanical ventilation – case 5. And this was due to aspergillosis. So I don’t think that any of the newer therapies would have made a difference in this cohort of patients
The RECOVERY trial has found that there are other treatment options that were effective in COVID 19 treatment as:
sotrovimab (a monoclonal antibody treatment against the spike protein)
molnupiravir (an antiviral treatment)
paxlovid (an antiviral treatment)
In addition, use of high dose dexamethasone ( 6mg once daily for 10 days or until discharge in hospitalized patients requiring oxygen (with or without non-invasive ventilation) and for patients on invasive mechanical ventilation or extra-corporeal membranous oxygenation (ECMO). As a consequence, dexamethasone 6 mg once daily is now widely recommended for treatment of such patients.
I think addition of dexa can be used for the case who required MV and CVVHF. Also use of new available drugs is worthy trying in severe cases as case with CVVH.
While in rest of cases with short hospitalization, I think no added treatment was required and (supportive therapy and stoppage of antiproliferative therapy remains the golden standard for managemnt )
_ also, tocioizumab was found to be non effective and increased mortality among SOT.
Dear Prof. Ahmad: You have noticed that I published this article before the publication of the results of the RECOVERY trial. Do you think I would have treated these patients differently?
Yes; in the followings:
(1) in the form of severe disease with cytokine storm you might give dexamethasone 6 mg for 10 days, with subsequent tapper down .
(2) Introduction of remdsivir early in the treatment of your patients.
(3) in severe case you might give Tocilizumab/ or baricitinib.
but the main stay of treatment would not differ in the form of supportive measures, immunosuppressive reduction/ or discontinuation
The short answer is no for most of the patient as general supportive was also helpful in many mild to moderate cases at that particular time. One patient was even treated as out patient.However, another patient required ICU & ventilatory support and the treatment of this one in my opinion would have been done according to recovery trial i.e IV dexamethasone 6 mg should it be published that time.
The recovery trial found that the use of dexamethasone in patients hospitalized with Covid-19, resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support. They found that also tocilizumab reduces the risk of deaths in patients hospitalized with severe COVID-19 infection, it shortens the time taken for patients to be successfully discharged from hospital, and reduces the need for a mechanical ventilator. The RECOVERY team also found that treatment with baricitinib reduced deaths by 13%. It also reduced the chance of progressing to invasive mechanical ventilation.
In this case series the treatment will not be different because all patients were mild to moderate cases except case number 5 who deteriorates and found to have aspergellosis and managed without specific antiviral , other wise all underwent supportive therapy ,reduction of immunosuppression stop antimetabolites and reduce the dose of tacrolimus .
RECOVERY had demonstrated 4 life-saving drugs including – dexamethasone, tocilizumab, baricitinib and casirivimab-imdevimab . In each case, results from RECOVERY were clear enough to rapidly influence global practice due to it’s particular setting in the UK during the SARS-CoV-2 pandemic also due to it’s generalisable contexts.
Reference
Leon Peto, Peter Horby, Martin Landray,Establishing COVID-19 trials at scale and pace: Experience from the RECOVERY trial,Advances in Biological Regulation,Volume 86,
2022,100901,
ISSN 2212-4926,
RECOVERY study as shown in attached figure there are another 4 drugs options including – dexamethasone, tocilizumab, baricitinib and casirivimab-imdevimab can be used in critically ill COVID patients.
in this article you discussed 8 cases
Only case 5 i think she may get benefits from Tocilizumab specially with high Serum interleukin-6 22.2 pg/mL (n = 0–7 pg/mL) but with good cover of antifungal and antimicrobial therapy.
The other 7 cases are considered mild to moderate cases and managment in the form of hold MMF and supportive management were excellent with outstanding outcomes.
Mild cases the same supportive care & reduction of immunosuppression
Severe case that need non invasive or invasive mechanical ventilation can benefit from low dose of dexamethasone that can reduce need of IMV & hospital stay.
Professor, COVID-19, unlike Influenza and other viral diseases, is a disease that courses with systemic vasculitis, including pulmonary vasculitis with evolution to Acute Respiratory Syndrome.
Withdrawing Mycophenolate is an excellent strategy to minimize immunosuppression to face the active viral disease and, consequently, the vasculitis process that it develops.
For Th2-response diseases and with vasculitic inflammatory disease, corticosteroids have always been a strategy to control the disease. The dose is dependent on the evolution and severity of the patient.
His vast knowledge of pathophysiology and the immune process of transplantation naturally led him to modulate the patient appropriately.
The RECOVERY Trial has found four treatments that are effective for severe COVID-19 dexamethasone, tocilizumab, baricitinib and casirivimab-imdevimab. In this article, among 8 cases, only case 5 might get benefits from Tocilizumab as high IL-6 level in a critically ill patient. Though this patient recovered with out those emerging treatment options.
In these cases 7/8 results from recovery trial would have no impacts on its management, so all the supportive care provided was enough.
Regarding 1/8 in ICU patient would have received DEXA according to recovery trial..
Thank you for the question, Prof. In these all cases except one would have no change in its management. Regarding one case in ICU patient would have received dexamethasone according to recovery trial.
I think yes especially in those cases which deteriorated. but not really in those who recovered with 2-4 days as they were mild cases.but adding dexamethasone to those which deteriorated would have helped faster recovery.
Prof I think only one patient which needed mechanical ventilation could have been treated differently ( use of dexa). In view of RECOVERY trial as such patients showed reduce mortality , rest of the patients had mild to moderate disease with no oxygen requirement and can be managed same way as u did .
Remdesivir is another thing which can be considered in these patients
the conclusion of recovery trial was :In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support.
accordingly sever COVID 19 infected patient may get benefit from dexamethasone treatment.
I do not think so since supportive therapy with IVF, monitoring kidney function, symptomatic treatment with oxygen depending on the oxygen saturation, reduction/ discontinuation of antiproliferative immunosuppressive agents seemed to work well for most patients apart from the one with severe disease who might have benefited from IV dexamethasone 6mg OD.
I do not think so since supportive therapy with IVF, monitoring kidney function, symptomatic treatment with oxygen depending on the oxygen saturation, reduction/ discontinuation of antiproliferative immunosuppressive agents seemed to work well for most patients apart from the one with severe disease who might have benefited from IV dexamethasone 6mg OD.
In RECOVERY trial showed that there is no benefit of remdisivir on reduction of mortality, only reduce period of hospitalization and dexamethasone reduce mortality those require oxygen.
In your study, you recommend remdisivir in hospital setting which is similar to RECOVERY trial.
IntroductionThe coronavirus disease 2019 (COVID-19) was an infection that led to a pandemic. It emerged in Wuhan city, China in December 2019. Kidney transplant recipients have a high risk of infection due to immune suppression and associated comorbidities. This report summarizes cases of kidney transplant recipients that were infected with COVID-19.
Case reportsPatient 1
A 21-year-old female had a kidney transplant in December 2019 from a deceased donor. She presented on March 30 with fever and lethargy. She had no respiratory symptoms and clinical examination was unremarkable apart from the fever. The chest x-ray was also clear she tested positive for COVID-19. She is hypertensive and usually maintained on calcium channel and beta blockers. Her regular immune suppression medications included prednisone, tacrolimus and mycofenolate mofetil (MMF). During admission she received supportive medical management and MMF was discontinued. She was discharged after two days with full recovery and stable kidney functions.
Patient 2A 71-year-old male with hypertensive nephropathy on calcium channel blockers and he received a kidney transplant in February 2016. He had a history of colon adenocarcinoma in 2019. His regular immune suppression medications included prednisone, tacrolimus and MMF. He presented on April 2, 2020 with a dry cough and stable vital signs his chest x-ray revealed battery bilateral consolidation and he was tested positive for COVID-19. His MMF is also discontinued and he received supportive IV fluids and symptomatic treatment. He was discharged two days later with stable kidney functions.
Patient 3A 50-year-old male underwent life donor kidney transplant in February 2020 due to a history of Wegner’s granuloma. His regular immune suppression medications included prednisone, tacrolimus and MMF. He presented on April 3 with a productive cough and was tested positive for COVID-19 infection. His chest xray was clear and kidney function tests were stable. His management also included discontinuation of MMF, reduction of tacrolimus dose and self isolation at home. He did not present with any further symptoms.
Patient 4Hey 63-year-old male with a history of IgA nephropathy, received a deceased donor kidney transplant in December 2005. He is also hypertensive on calcium channel blockers. He presented on March 20 with fevers and acute kidney injury. The chest x-ray showed bilateral consolidation. The patient tested positive for COVID-19 infection, and blood culture was positive for staphylococcus aureus. His regular immune suppression medications included prednisone, tacrolimus and MMF. The patient required admission and received IV antibiotics and paracetamol. MMF was stopped and the tacrolimus doors was increased. The patient recovered, and an improvement of kidney function was noted.
Patient 5A 47 year old female with bronchial asthma received a deceased donor kidney transplant in December 2019. Her regular immune suppression medications included prednisone, tacrolimus and MMF. She presented in April with a dry cough and shortness of breath. Her chest x-ray showed bilateral middle and lower zone consolidation. She was tested positive for COVID-19 infection and acute kidney injury. Her urine culture was positive for E. coli infection, and her blood culture was negative. The patient’s respiratory function deteriorated, and she required invasive ventilation. Bronchoalveolar lavage showed growth of aspergillus. She required antibiotics and antifungals. Her MMF was discontinued, her kidney functions deteriorated and she became anuric. She required CVVH. She was weaned of mechanical ventilation after 14 days and transferred to the medical ward. Her kidney functions gradually improved. She was discharged home and CVVH was discontinued.
Patient 6A 71-year-old female with type two diabetes received a deceased donor kidney transplantation in 2015. Her regular immune suppression medications included prednisone, tacrolimus and MMF. She presented in April with a fever and no other complaints her chest x-ray showed bilateral peripheral mid and lower zone consolidation. She was tested positive for COVID-19 infection. She was admitted for hydration and symptomatic treatment. MMF was discontinued. She was discharged after four days with full recovery.
Patient 7A 40 year old female with hypertension, received a deceased donor kidney transplantation in 2017. Her regular immune suppression medications included prednisone, tacrolimus and MMF. She was also amlodipine for her hypertension. She presented in April with a fever and dry cough. She was tested positive for COVID-19 infection. MMF was discontinued paracetamol and fluids were administered and she was discharged after four days with full recovery.
Patient 8A 38 year old male with a failing kidney transplant in 2013 presented with a productive cough and shortness of breath for two days. His regular immune suppression medications included prednisone, tacrolimus and azathioprine. He was tested positive for COVID-19 infection. His kidney function test remained unchanged. His chest x-ray revealed bilateral infiltrates. And his management included discontinuation of azathioprine, reducing tacrolimus dosage and increasing prednisone. He did not require dialysis. Oxygen saturation improved and he was discharged after two days.
DiscussionEight cases were summarized in this review. The review included patients with kidney transplant who got infected with COVID-19. The median age of the patients was 48.5 years. There were four males, and four females. Three patients had kidney transplantation within the last three months of the review and the rest of the patients had been transplanted for more than a year.
The most common initial symptoms were fever and cough. All 8 patients were on tacrolimus and prednisone. 7 patients were on mycophenolate and one patient was on azathioprine. In all the patients the antimetabolite was stopped. No patients received any antiviral agents. All 8 patients recovered.
The one patient that required mechanical ventilation was also infected with fungal infection.
Transplant patients are at a high risk of infection, due to immune suppression, chronic kidney disease, associated comorbidities which include diabetes and hypertension.
When managing immunosuppression in post-transplant patients the age, duration of transplant, rejection of episodes and the severity of the COVID infection needs to be taken in to account. Every patient needs to be individualized.
In general, for mild infections, the usual practice is to continue or reduce the dose of immune suppression. Since the review only looked at eight patients, they are unable to provide recommendations. The treatment should be individualized based on the assessment of each patient.
ConclusionIn this report, the presentation of COVID-19 infection in renal transplant patients was not different from that of the general population. The transplant population did not behave differently from the general population in the duration of the COVID-19 infection. Due to the small sample size it was difficult to evaluate the effect of immune suppression during the course of the disease.
Level of Evidence: This is a case series so this is level IV
Impact Factor of A Journal:
This is a scientometric index calculated by clarivate the calculates the yearly mean number of citations of articles published in the previous 2 years.
It is used to measure the importance or rank of a journal by calculating the number of times its articles are cited
Please summarise this article.8 cases of COVID-19 in kidney transplant Sheffield Kidney experience reports .
The median age of patients was 48.5 years
4 males and 4 females.
Three patients had kidney transplantation within the last 3 months, and the rest were transplanted for more than a year.
The most common initial symptoms were fever (5 patients) and cough (5 patients).
All 8 patients were receiving prednisone and tacrolimus, 7 patients were receiving mycophenolate mofetil, and 1 patient was receiving azathioprine.
Two patients had AKI 1 of them required continuous veno-venous hemofiltration
Blood results all patients had lymphopenia and high CRP. Three patients had elevated serum ferritin, and 1 patient had high serum interleukin-6 (IL-6).
A portable chest X-ray was performed in 7 patients, which was clear in 2 of them, and the rest had a picture consistent with viral pneumonia.
One of our 8 patients was managed as an outpatient and advised to self-isolate at home, with the remaining 7 requiring hospital admission.
One patient required ITU admission, needed mechanical ventilation Bronchoalveolar lavage of this patient confirmed aspergillosis receiving antifungal treatment . Another patient required ward-based oxygen therapy The other 6 patients received supportive therapy on the renal ward (intravenous fluid therapy, monitoring renal function, and symptomatic treatment
Antiproliferative immunosuppressive drugs were discontinued for all patients.
studies Facts /hints
Transplant patients are at a high risk of infection due to multiple risk factors, including immunosuppression, underlying CKD, and associated comorbidities
hypertensive and diabetic patients have a double-fold risk of infection, while COPD patients have a 5-fold risk.
Liang et al. reported that 1% of COVID-19 patients had a history of malignancy,the most frequent tumour was lung cancer
the incidence of malignancy was 0.9% among their reported COVID-19 patients
Two large studies demonstrated that 82–87% of their patients had a fever, while patients with cough ranged from 44 to 65.7%
Early studies reported that the incidence of AKI was low (3–9%) in those with COVID-19 infection However, recent studies showed a higher frequency of renal abnormalities.
Cheng et al. reported that among 710 patients, 44% had proteinuria, 26.7% had haematuria, and 14.1% had high serum Cr.
The pathophysiology of renal involvement is still unclear, but theories suggest a cytokine storm syndrome or direct renal injury by the virus. Scientists succeeded in isolating SARS-CoV-2 from a urine sample of an infected patient, suggesting the kidney can be a target of this virus
cases of AKI associated with SARS and MERS, continuous renal replacement therapy was assumed that high-volume hemofiltration could remove inflammatory cytokines (tumour necrosis factor, IL-6, and IL-1β) involved in the pathogenesis of renal injury
Guan et al.reported that 83.2% of infected patients had lymphopenia on admission. Another study suggested a link between lymphopenia and acute respiratory distress syndrome (ARDS) development
Guan et al. reported that 60.7% of patients had an elevated CRP, while severe cases had a higher level compared to the non-severe ones (81.5 vs. 56.4% for CRP).
Many reports suggested that higher serum ferritin is associated with ARDS development and death
IL-6 is considered a novel biomarker for COVID-19 diagnosis.
.Chen et al. reported that 52% (51/99) of patients had high IL-6 levels on admission. Other studies suggested that increased IL-6 levels can be associated with an increased risk of mortality . Since we are not sure about the sensitivity and the specificity of IL-6, we did not measure it routinely. Also, there is no clear evidence to support the role of IL-6 blocker (tocilizumab) in treatment of COVID-19 in both transplant and non-transplant population.
The Italian and British hospitals employ chest X-ray as a first-line triage tool as the results of COVID-19 testing may take more time
The British Society of Thoracic Imaging (BSTI) issued guidelines which state that there is no recommended use of CT unless there is high suspicion with normal or uncertain appearance of CXR in a seriously ill patient
in mild infections,reduce the dose of immunosuppressive drugs. suggest discontinuation of the antiproliferative drugs (azathioprine and mycophenolate mofetil) while monitoring the patients closely.
In severe cases requiring mechanical ventilation, we can argue about ceasing calcineurin inhibitors while maintaining corticosteroid therapy. Undoubtedly, the treatment should be individualized based on the careful assessment of each patient.
the US Food and Drug Administration has authorized the use of remdesivir as a treatment option for hospitalized COVID-19 patients
What is the level of evidence provided by this article? Grade of Recommendation c
Level of Evidence 4
What is meant by the impact factor of a journal? is an index that measures how often a journal’s articles are cited in other research. This is calculated by the number of citations received by articles published in that journal during the two preceding years, divided by the total number of articles published in that journal during the two preceding years. You can find the journal Impact Factor on the journal homepage.
Summarise this article.There is a common belief among transplant clinicians that kidney transplant recipients have a high risk of infection due to long-term immunosuppression and associated comorbidities. This short series demonstrates experience in managing COVID-19 disease in renal transplant patients in the absence of strong evidence.
8 cases of kidney transplant recipients infected with COVID-19
median age = 48.5 years; range = 21–71 years
4 males and 4 females
The most frequently associated comorbidity was hypertension.
The most common presenting features were fever and cough.
The main radiological investigation was a portable chest X-ray.
Other common features included lymphopenia, high C-reactive protein, and a very high ferritin level.
Overall, 1 patient was managed as an outpatient, the remaining 7 required hospital admission, 1 of them referred to the intensive therapy unit.
Management included intravenous fluid therapy, monitoring renal function, and symptomatic treatment with or without ward-based oxygen therapy depending on oxygen saturation
Discontinuation of the antiproliferative immunosuppressive drugs.
Seven patients recovered and discharged home to self-isolate.
One patient required intensive care treatment and mechanical ventilation.
Non had antiviral treatment
Discussion Transplant patients are at a high risk of infection due to multiple risk factors, including immunosuppression, underlying CKD, and associated comorbidities.
Hypertensive and diabetic patients have a double-fold risk of infection, while COPD patients have a 5-fold risk.
The pathophysiology of renal involvement is still unclear, but theories suggest a cytokine storm syndrome or direct renal injury by the virus. Continuous renal replacement therapy may play a role in the management of AKI in COVID-19 patients.
Lymphopenia, High CRP and Ferritin levels are associated with ARDS and poor outcomes.
No clear evidence to support the role of IL-6 blocker (tocilizumab) in treatment of COVID-19 in both transplant and non-transplant population.
It is also essential for clinicians of all specialities to be familiar with the radiological findings of COVID-19 on chest X-ray
Discontinue the antiproliferative drugs (azathioprine and mycophenolate mofetil) while monitoring the patients closely.
In severe cases requiring mechanical ventilation, stop calcineurin inhibitors while maintaining corticosteroid therapy
Conclusions Presentations of COVID-19 infected renal transplant patients is not different from the general population
Supportive treatment could be sufficient or at least to be tried first
Short hospital stay with self-isolation on discharge reduces the burden on the health service and protect the staff and the public
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current EvidenceSummarize the article.
COVID 19 IN RENAL TRANSPLANT RECIPIENTS;CASE SERIES AND A BRIESF REVIEW OF CURRENT EVIDENCE.
Introduction.
Covid 19 has genomic similarities to SARS COV and MERS COV.It has affected multiple countries and resulted to mortalities but we dont have enough data on the transplant popn.
Case reports;
Pt 1 – 21yr old who presented 4/12 post transplant with resp symptoms and a covid 19 +VE ,He recovered and was discharged in 2/7 after MMF was stopped and got supportive tx.PDL and Tac was maintained.
Pt 2 -71 yr old hypertensive nephropathy who dev colon adeno ca post transplant and presented 4 yrs post transplant with resp symptoms, CXR had infiltrates and Covid 19 PCR was +VE,MMF was stopped, He got supportive tx and was discharged in 2/7 with stable kidney function. PDL and Tac were maintained
Pt 3 – 50yr old with hx of Wegner granulomatosis who presented 2 months post transplant with resp symptoms and a +VE Covid 19.MMF was stopped and Tac reduced and pt advised on self isolation at home..
Pt 4 – 63yr old, previous IGA nephropathy who presented 5yrs post transplant with resp symptoms ,AKI,CXR with consolidation and Covid 19 PCR +VE. He was admitted ,put on broad spectrum antibiotics for an infection, MMF was stopped, Tac increased, PDL was maintained, He recovered and went home in a week.
Pt 5 – 47 yr old with asthma who presented 5/12 post transplant with resp symptoms, CXR had consolidation ,Covid 19 PCR was +VE and had an AKI, She was admitted to ICU for CPAP, Had aspergillus infection on BAL.MMF was stopped, CRRT initiated, antivirals given, CRRT later stopped and pt discharged with a GFR of 17 1/52 later.
Pt 6 -71yr old DM female who presented 6 yrs post transplant with fever, CXR had consolidation, Covid 19 +VE, got symptomatic tx,MMF discontinued while PDL and Tac maintained. He got well and was discharged in 4/7.
Pt 7 – 40yr old HTN pt who presents 4 yr post transplant with resp symptoms, Covid 19 PCR was +VE,MMF was stopped, PDL and Tac maintained. She got symptomatic mgt and was discharged after 4/7.
Pt 8 – 38 yr old male 8 yr post transplant who presented with fever and resp symptoms, CXR had consolidation, Covid 19 PCR +VE,AZA was stopped, PDL and Tac maintained and offered supportive tx, He was later discharged after 2/7.
Discussion.
-Fever and cough were the most prominent symptoms for Covid in the listed cases.
-Aspergillosis is a potential complication in this cohort and can contribute to poor outcomes if not addressed.
-Multiple comorbidities in transplant pts increases risk of infection.
-The role of CRRT to decrease inflammatory cytokines can be explored in AKI cases with good outcomes in Covid pts with AKI.
-Lymphopenia and high CRP on admission has poor outcomes post covid, Ferritin is an acute phase reactant not sensitive and specific as a prognostic marker.
-More studies needed on IL6 as a novel marker and use of toclizumab in Covid 19 pts.
-Portable CXR recommended to decrease chance of transmission and CT Scan used when CXR are not clear.
-In mild infection; continue or discontinue immunosuppressive medication, in this case, anti proliferative agent stopped initially while monitoring graft function, In sever cases CNIs are either decreased or stopped. Steroids are maintained and tx is always individualized.
-The efficacy of convalscent plasma in Covid pt is not clear.
-In non transplant pts, Remedesevir has shown quick recovery in covid pts,we need more studies before it can be applied broadly including in transplant popn
What is the level of evidence provided by this article?
-LEVEL IV – Case Series.
What is meant by the impact factor of a journal?
This is the average number of tomes that an article has been cited in its particular field/speciality over a 2 yr span of time.
I appreciate your well-structured summary in great details, and conclusions. I make note of the level of evidence that you have allocated to this article on COVID19 virus in renal transplant.
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
1. Please summarise this article.2. What is the level of evidence provided by this article?3. What is meant by the impact factor of a journal? Please summarise this article:
Introduction:
COVID-19 has close genomic structural similarities to SARS-CoV and MERS-CoV and has caused 203,818 reported deaths worldwide. 8 cases of kidney transplant recipients infected with COVID-19 due to long-term immunosuppression and comorbidities have been reported.
Case Reports
Patient 1
Had a deceased donor kidney transplant in December 2019 and presented with a high fever and no respiratory symptoms.
A nasal and throat swab for COVID-19 tested positive and she was on prednisone, tacrolimus, and mycophe-nolate mofetil.
Patient 2
A 71-year-old male with hypertensive nephropathy had a history of colon adenocarcinoma and was on immunosuppressive medications, but was tested positive for COV-ID-19.
Patients 3, 4, and 5 received live donor kidney transplants in February 2020, February 2019, and December 2019 respectively.
Patient 3 was test-ed positive for SARS-CoV-2 RNA despite unremarkable clinical examination, and his immunosuppressive drugs were prednisolone 5 mg OD, tacrolimus (trough level was 13.4 ng/mL), and MMF 500mg BD.
He was advised to drink plenty of fluids and report to the unit any new symptoms.
Patient 4 was a 63-year-old male with a history of IgA nephropathy with a deceased donor kidney transplant in December 2005.
He was admitted and received IV broad-spectrum antibiotics and paracetamol.
Patient 6:
A 71-year-old female with type II diabetes received de-ceased donor kidney transplantation in November 2015.
Her kidney functions deteriorated and continuous veno-venous hae-modiafiltration (CVVH) was commenced.
On April 2, she presented with fever (38.5°C) and no other complaint. Chest X-ray showed bilateral peripheral mid and lower zone consolidation.
Nasal and throat swabs were positive for COVID-19 RNA. Kidney function tests showed no change from baseline, and microbiological tests were negative.
She was admitted to the medical ward for adequate hydration and symptomatic treat-ment.
Patient 5 received a deceased donor kidney transplant in December 2019 and presented on April 6 with dry cough and shortness of breath.
Chest X-ray showed bilateral middle and lower zone consolidation, and SARS-CoV-2 RNA was positive.
Kidney function tests showed AKI, mild proteinuria, and leu-kocytosis. Microbiology workup showed positive urine culture for E.coli and negative blood culture.
Patient 6 was a 71-year-old female with type II diabetes who received a deceased donor kidney transplantation in November 2015.
On admission, her serum CRP was 344 mg/L and ferritin 2684 μg/L, with leu-kocytosis, lymphopenia, and interleukin-6.
Bronchoalveolar lavage showed moderate growth of aspergillus, and she received broad-spec-trum antibiotics and antifungals. Her kidney functions deteriorated, and continuous veno-venous hae-modiafiltration (CVVH) was commenced.
After 14 days, she was weaned off mechanical ventilation and transferred from the ITU to the medical ward.
Kidney function tests showed no change from baseline, and microbiological tests were negative.
Patient 4 was a 63-year-old male with a history of IgA nephropathy with a deceased donor kidney transplant in December 2005.
His immunosuppressive drugs were prednisolone 5 mg OD, tacrolimus (trough level was 13.4 ng/mL), and MMF 500mg BD. He presented on March 20 with fever and acute kidney in-jury (AKI).
Chest X-ray showed patchy bilateral consolidation, and SARS-CoV-2 RNA was positive.
He was admitted and received IV broad-spectrum antibiotics and paracetamol.
Kidney function tests improved (serum Cr de-creased to 113 μmol/L). He recovered and discharged home after 7 days.
Patient 6 was a 71-year-old female with type II diabetes who received de-ceased donor kidney transplantation in November 2015.
On April 2, she presented with fever (38.5°C) and no other complaint.
Chest X-ray showed bilateral peripheral mid and lower zone consolidation.
Kidney function tests showed no change from baseline, and microbiological tests were negative.
MMF was discontinued and discharged after 4 days with full recovery.
Discussion
This report presents 8 cases of COVID-19 infection in kidney transplant patients from Sheffield Kidney Institute, UK.
The median age of the patients was 48.5 years and the most common initial symptoms were fever (5 patients) and cough (5 patients).
All 8 patients were receiving prednisone and tacrolimus, 7 patients were receiving mycophenolate mofetil, and 1 patient was receiving azathioprine.
Blood results showed that all patients had lymphopenia and high CRP.
A portable chest X-ray was performed in 7 patients, which was clear in 2 of them, and the rest had a picture consistent with viral pneumonia.
One patient required ITU admission, one patient required mechanical ventilation, and one patient required ward-based oxygen therapy.
Antiproliferative immunosuppressive drugs were discontinued for all patients due to multiple risk factors, including immunosuppression, underlying CKD, and associated comorbidities.
Lianget al. [11] reported that 1% of COVID-19 patients had a history of malignancy, which was higher than the preva-lence of cancer in the overall Chinese population (0.29%).
The most frequent tumour was lung cancer, and the most frequent presentation was fever (5 patients) and cough (5 patients).
Two large studies demonstrated that 82-87% of their patients had a fever, while patients with cough ranged from 44 to 65.
Two of our patients had AKI, and the pathophysiology of renal involvement is still unclear, but theories suggest a cytokine storm syndrome or direct renal injury by the virus.
Scientists succeeded in isolating SARS-CoV-2 from a urine sample of an infected patient.
COVID-19 infection is associated with high CRP and lymphopenia, which can lead to adverse outcomes such as ARDS development, myocardial damage, and death.
Continuous renal replacement therapy may play a role in themanagement of AKI in COVID-19 patients.
Serum ferritin is an acute-phase protein, but its sensitivity and specificity are unknown.
IL-6 is considered a novel biomarker for COVID-19 diagnosis, but it is not routinely measured and there is no clear evidence to support the role of IL-6 blocker (tocilizumab) in treatment.
Chest X-ray was used as a first-line triage tool, but CT decontamination may disrupt service availability and portable chest X-ray should be considered to reduce transmission.
CT is not recommended unless there is high suspicion of CXR in a seriously ill patient, and it is important to be familiar with the radiological findings of COVID-19 on chest X-ray.
When managing immunosuppression in kidney transplant recipients, the age, severity of infection, post-trans-plant duration, any other associated comorbidity, tissue mismatch, and any episodes of rejection should be considered.
The treatment should be individualized based on the careful assessment of each patient.
The US Food and Drug Administration has authorized the use of remdesivir as a treatment option for hospitalized COVID-19 patients. Conclusion
The presentations of COVID-19-infected renal transplant patients were similar to the general population, with fever and cough being the most frequent symptoms.
Supportive treatment could be sufficient, and short hospital stay with self-isolation on discharge reduces the burden on the health service and protects the public.
Treatment with remdesivir should be done in a hospital setting with CNI drug level monitoring. What is the level of evidence provided by this article?
The level evidence is IV
What is meant by the impact factor of a journal?
The impact factor (IF) is a measure that reflects the average number of citations to articles published in journals, books, thesis, project reports, newspapers, conference/seminar proceedings, documents published in internet, notes, and any other approved documents.
It is used to evaluate the relative importance of a journal within its field and to measure the frequency with which the “average article” in a journal has been cited in a particular time period.
Journals with higher IFs are believed to be more important than those with lower ones. Journal which publishes more review articles will get maximum IFs.
Impact factor (IF) is the average number of citations received per article published in a journal during the 2 preceding years.
It is calculated each year by Thomson scientific for those journals that it indexes, and is published in Journal Citation Reports .
For example, if a journal has an IF of 3 in 2008, then its papers published in 2006 and 2007 received three citations each on average in 2008.
The IF of any journal may be calculated by the formula;2012 impactfactor =A/BWhere A is the number of times articles published in 2010 and 2011 were cited by indexed journals during 2012.
In an ideal world, evaluators would read each article and make personal judgments.
I make note of of your suggestion ‘In an ideal world, evaluators would read each article and make personal judgments.’ But is it really possible without AI to go through almost 6000 medical journals every month. I agree with your implied message as I would understand: ‘henceforth, we rely on every else each with specific interest in their respective articles and calculate mathematically to express popularity of journals’.
I like your well-structured summary in great details, and conclusions. I appreciate level of evidence that you have allocated to this article on COVID19 virus in renal transplant.
Introduction:
The novel COVID-19 infection, which arose in Wuhan, China, in December 2019, shares genomic structural similarities with the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused the 2003 SARS pandemic and the 2012 MERS pandemic. COVID-19 infected 210 nations and killed 203,818 persons till April 26, 2020.
30,000 UK deaths have occurred.
it is believed that kidney transplant recipients have a high infection risk due to long-term immunosuppression and comorbidities. COVID-19 in renal transplant recipients is poorly studied.
so, this is a case reports of 8 cases of COVID-19 in post kidney transplant. Patient 1: a 21-year-old female with a deceased donor kidney transplant in December 2019 arrived on March 30 with fever (39.2°C). No respiratory symptoms, she felt lethargic and ill. Except a high temperature, the chest X-ray and clinical examination were normal.
Negative blood and urine cultures. Positive COVID-19 nose and throat swabs. was on CCB and β-blockers for hypertension, prednisone 5 mg od, tacrolimus 2 mg twice a day, and mycophenolate mofetil 250 mg (BD). stopped MMF & Intravenous fluids &supportive measures. Discharged after 2 days with stable RFTs. Patient 2: 71-year-old male with hypertensive nephropathy who had a kidney graft in February 2016. June 2019 colon adenocarcinoma history. Baseline Cr was 240–260 μmol/L. presented with respiratory symptoms & spotty bilateral consolidation. He was admitted after a positive COVID-19 swab. MMF stopped and had IV hydration and symptomatic therapy. He left two days later with stable kidney functions. Patient 3: also responded to holding MMF & supportive management with self-isolation at home. Patient 4: 63-year-old male with IgA nephropathy and a deceased donor kidney transplant in December 2005. Calcium channel blockers control his hypertension. presented with a fever (38.8°C) and AKI; Cr 297 μmol/L, baseline 110). SARS-CoV-2 RNA was positive, and the chest X-ray exhibited patchy bilateral consolidation. Blood culture showed staphylococcus aureus. CRP was 175 mg/L and ferritin 929 μg/L. Prednisolone 5 mg OD, tacrolimus (2.7 ng/mL), and MMF 500 mg BD were his immunosuppressive drugs. The patient was hospitalised for IV broad-spectrum antibiotics and paracetamol. stopped MMF and increased tacrolimus. Kidney function improved (serum Cr dropped to 113 μmol/L). After 7 days, the patient was home. Patient 5: A 47-year-old bronchial asthmatic woman received a deceased donor kidney transplant in December 2019. came with respiratory symptoms& x-ray findings.
COVID-19-positive. AKI and moderate proteinuria. E. coli was found in urine but not blood. On admission, serum CRP was 344 mg/L and ferritin 2684 μg/L, with leucocytosis (white cell count 25.8 × 109/L) and lymphopenia (lymphocyte count 0.7 × 109/L). Interleukin-6 was 22.2 pg/mL. She was admitted to ICU for non-invasive ventilation (CPAP for type 1 respiratory failure). needed intubation and invasive ventilation. Aspergillus moderated in bronchoalveolar lavage. got broad-spectrum antibiotics and antifungals. No antivirals were administered. MMF stopped. She got anuric and needed CVVH. She was transferred from the ICU to the medical ward after 14 days of mechanical ventilation. Her renal functions improved and CVVH stopped. She left 7 days later.
The other 3 patients also responded to supportive measures plus holding antiproliferative drugs. Discussion:
This paper describes 8 COVID-19 infections in kidney transplant patients. Four males and four females were 48.5 years old (range from 21 to 71 years). Three patients underwent kidney transplants within three months, and the remainder were transplanted over a year ago. Fever and cough were the most common early symptoms (5 cases) (5 patients). 8 individuals received prednisone and tacrolimus, 7 received mycophenolate mofetil, and 1 received azathioprine. Cases 4 and 5 had AKI, and one needed CVVH (case 5).
Patients experienced lymphopenia and elevated CRP. Three individuals had elevated ferritin, and one had high interleukin-6. Two of seven patients had clear chest X-rays, while the rest had viral pneumonia.
One was outpatient and recommended to self-isolate at home, while the other 7 were hospitalized. One Icu patient needed mechanical ventilation (case 5). She is being treated for aspergillosis after bronchoalveolar lavage (another contributing factor for deterioration). Case 8 needed ward-based oxygen. The remaining 6 patients got supportive care on the renal ward (intravenous fluid therapy, monitoring renal function, and symptomatic treatment with or without ward-based oxygen therapy based on oxygen saturation). All patients stopped antiproliferative drugs.
Immunosuppression, CKD, and comorbidities such hypertension and diabetes put transplant patients at risk of infection. Fever and cough were the most common symptoms in our case series (5 patients). Cough followed fever as the most prevalent symptoms. AKI was rare (3–9%) in COVID-19-infected patients. Recent studies found more renal affection. Cheng et al. found 44% proteinuria, 26.7% haematuria, and 14.1% elevated serum Cr in 710 individuals. Cytokine storm syndrome or virus-induced renal damage may explain renal involvement. SARS-CoV-2 was isolated from a patient’s urine, suggesting it targets the kidney.
Continuous renal replacement therapy improved SARS and MERS-related AKI. High-volume hemofiltration was thought to remove inflammatory cytokines (TNF, IL-6, and IL-1β) that cause kidney damage. Hence, continuous renal replacement treatment may treat COVID-19 AKI.
All patients had lymphopenia and elevated CRP. Guan et al. found lymphopenia in 83.2% of infected patients on admission. Another study linked lymphopenia to ARDS.
Several studies linked COVID-19 to elevated CRP. Guan et al. [5] found that 60.7% of patients had raised CRP, with severe cases having a higher CRP (81.5 vs. 56.4%). High CRP has been linked to adverse outcomes like ARDS, myocardial injury, and mortality. Several studies linked increased serum ferritin to ARDS and death. The outcome sensitivity and specificity of ferritin, an acute-phase protein, remain unknown.
Novel COVID-19 biomarker IL-6. Case 5 was high. Chen et al. [20] found 52% (51/99) of patients had elevated IL-6 on admission. Several investigations linked higher IL-6 levels to higher mortality.
7 individuals had chest X-rays. Five exhibited bilateral patchy consolidation, and two had no COVID-19 symptoms. CT findings dominated COVID-19 radiological findings. This approach burdened radiology departments and made radiology suite infection management difficult, hence the American College of Radiology recommends portable chest X-ray to minimize infection.
Because COVID-19 testing takes time, Italian and British hospitals use chest X-rays for triage. The British Society of Thoracic Imaging (BSTI) recommends CT only for high suspicion with normal or unclear CXR in very sick patients.
6 patients stopped their antiproliferative medicines and underwent supportive treatment; 1 needed oxygen therapy, and 1 needed mechanical ventilation. No patients received particular antiviral medications. Kidney transplant recipients should consider age, infection severity, post-transplant length, comorbidities, tissue mismatch, and rejection episodes. With minor infections, immunosuppressive medications are usually continued or reduced. Despite the study’s limited sample size, we recommend discontinuing azathioprine and mycophenolate mofetil and closely monitoring patients. In severe infections, stop antiproliferative medications first, especially in the absence of UK guidelines and the unpredictable course of COVID-19 infection in this population. Calcineurin inhibitors can be stopped while corticosteroids are continued in severe patients requiring mechanical ventilation. Personalized treatment based on patient assessment is essential. Convalescent plasma was utilized to treat SARS patients. A meta-analysis found that many trials had small sample sizes and no control groups, casting doubt on its usefulness.
Chu and colleagues found no benefit with lopinavir and ritonavir in SARS-CoV patients. Additional studies showed that remdesivir, a broad-spectrum antiviral nucleotide prodrug, can treat MERS-CoV and SARSCoV. the FDA has approved remdesivir for hospitalized COVID-19 patients. Conclusion:
fever and cough were the most frequent symptoms.
supportive treatment could be sufficient or at least to be tried first.
recommend treatment with remdisivir in a hospital setting where CNI drug level monitoring is available. Level of evidence:
Level 4, case series Impact factor of a journal:
used to measure the frequency with which the “average article” in a journal has been cited in a particular time period, which in turn reflect the potency & importance of the journal.
calculated based on a two-year period via dividing the number of citations by the number of citable articles.
I like your well-structured summary in great details, and conclusions. I appreciate level of evidence that you have allocated to this article on COVID19 virus in renal transplant.
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
Case Reports Patient 1 Scenario
· 21-year-old hypertensive female had a DD kidney transplant in December 2019.
· Presented around 3 months post- transplant with fever 39.2°C, lethargic and generally unwell.
· No respiratory symptoms and Clinical examination was unremarkable.
· Chest X-ray was clear, urine and blood cultures were negative.
· A nasal and throat swab for COVID-19 tested positive.
· She was on prednisone, tacrolimus and MMF 250 mg. Management:
· Admitted and received supportive medical treatment.
· MMF was discontinued Outcome:
· Discharged after 2 days with full recovery and stable kidney functions. Patient 2: Scenario
· 71-year-old hypertensive male received a kidney graft in February 2016.
· History of colon adenocarcinoma in June 2019.
· His baseline Cr was 240–260 μmol/L.
· IS regimen included prednisolone 5 mg OD, tacrolimus (trough level was 6.4 ng/mL), and MMF 250 mg BD.
· Presented with a dry cough, no other symptoms and stable vital signs.
· Chest X-ray: patchy bilateral consolidation.
· positive for COVID-19 Management
· Admitted to hospital.
· MMF discontinued and received supportive treatment. Outcome
· Discharged 2 days later with stable kidney functions. Patient 3: Scenario
· 50-year-old male received a live donor kidney transplant in February 2020.
· IS drugs were prednisolone 5 mg OD, tacrolimus (trough level was 13.4 ng/mL), and MMF 500 mg BD
· Presented 2 months after transplantation with productive cough.
· Chest X-ray was clear
· Tested positive for SARS-CoV-2 RNA.
· Kidney function tests were stable. Management
· Discontinuation of MMF, reduction of tacrolimus dose.
· Self-isolation at home. Patient 4: Scenario
· 63-year-old hypertensive male, DD kidney transplant in December 2005.
· Presented on March 20 with fever (38.8°C) and AKI; Cr 297 μmol/L, baseline 110 μmol/L).
· The chest X-ray showed patchy bilateral consolidation.
· SARS-CoV-2 RNA was positive.
· IS regimen was prednisolone 5 mg OD, tacrolimus (trough level was 2.7 ng/mL), and MMF 500 mg BD. Management
· Admission and received IV broad-spectrum antibiotics and paracetamol.
· Stopped MMF and increased the tacrolimus dose. Outcome
· Kidney function tests improved
· The patient recovered and discharged home after 7 days. Patient 5: Scenario
· 47-year-old female with bronchial asthma received a DD kidney transplant in December 2019.
· She was maintained on prednisolone 5 mg OD, tacrolimus with levels between 5 and 7 ng/mL, and MMF 250 mg BD.
· She presented with dry cough and shortness of breath but no fever.
· Chest X-ray: bilateral middle and lower zone consolidation.
· COVID-19 test positive.
· AKI (Cr 302 μmol/L and baseline 162 μmol/L), and mild proteinuria (urine protein/Cr ratio 127 mg/ mmol and baseline <30 mg/mmol).
· Microbiology workup showed positive urine culture for E. coli and negative blood culture.
· She was tachypnoeic with a respiratory rate of 36 breaths/min, and the peripheral oxygen saturation was 80% Management
· Admitted to the ITU) for CPAP
· Her respiratory functions got worse and she required invasive ventilation.
· Bronchoalveolar lavage showed moderate growth of aspergillus.
· She received broad-spectrum antibiotics and antifungals.
· MMF was discontinued.
· Her kidney functions deteriorated, and received CVVH. Outcome
· After 14 days, she was weaned off mechanical ventilation.
· Her kidney functions improved (estimated glomerular filtration rate was 17 mL/min per 1.73 m2, urine protein/Cr ratio, 40 mg/mmol).
· She was discharged 7 days later. Patient 6: Scenario
· A 71-year-old female with type II diabetes, DD kidney transplantation in November 2015.
· IS therapy included prednisolone, tacrolimus, and MMF.
· Presented with fever (38.5°C) and no other complaint.
· Chest X-ray showed bilateral peripheral mid and lower zone consolidation.
· Swabs were positive for COVID-19 RNA.
· Kidney function tests showed no change from baseline, and microbiological tests were negative. Management
· Admitted to the medical ward for adequate hydration and symptomatic treatment.
· MMF was discontinued. Outcome
· Discharged after 4 days with full recovery. Patient 7: Scenario
· 40-year-old hypertensive female received DD kidney transplantation in June 2017.
· Maintained on prednisolone, tacrolimus, and MMF.
· she presented with fever (39°C) and dry cough with no other symptoms
· Swabs for COVID-19 RNA were positive.
· Kidney function tests were stable and microbiological analyses were negative. Management
· Admitted to the medical ward.
· MMF was discontinued, Paracetamol and IV fluids were administered.
Outcome
· Discharged after 4 days with full recovery. Patient 8: Scenario
· 38-year-old male with a failing kidney transplant.
· Presented with productive cough and shortness of breath for 2 days.
· Maintained on prednisolone 5 mg OD, tacrolimus, and azathioprine.
· He had tachypnoea and oxygen saturation of 89% on room air, which improved on oxygen through a nasal cannula.
· Swabs were positive for COVID-19 RNA.
· Kidney function tests remained unchanged despite the high baseline Cr.
· Chest X-ray; bilateral infiltrates.
Management
· Discontinuation of azathioprine, reduction of tacrolimus dose, and increase of prednisolone dose to 15 mg OD. Outcome
· He did not require any dialysis.
· Oxygen saturation recovered
· The patient was discharged after 2 days. Discussion
· In this report, 8 cases of COVID-19 infection in kidney transplant patients were reported from Sheffield Kidney Institute, UK.
· The most common initial symptoms were fever and cough.
· All patients were receiving prednisone and tacrolimus, 7 patients were receiving mycophenolate.
· Two patients had AKI 1 of them required CVVH.
· CCVH showed promising results in AKI associated with SARS and MERS. It could remove inflammatory cytokines involved in the pathogenesis of renal injury.
· All patients had lymphopenia and high CRP.
· CXR in most of them had a picture consistent with viral pneumonia.
· One was managed as an outpatient and one patient required ITU admission. Aspergillosis was confirmed in the latter.
· Transplant patients are at a high risk of COVID 19 due to multiple risk factors, including immunosuppression, underlying CKD, and associated comorbidities, especially hypertension and diabetes.
· Five out of seven patients had bilateral patchy consolidation in CXR. Which suggest viral infection, the recommendation is to use portable chest X-ray to reduce the transmission of infection rather than CT chest.
· Regarding IS, in 6 of these patients, antiproliferative drugs were stopped. They recommended the treatment should be individualized based on the careful assessment of each patient.
· In this series, none of the patients received specific antiviral drugs.
· In some studies, remdesivir showed promising results. Based this results, the FDA has authorized the use of remdesivir as a treatment option for hospitalized COVID-19 patients with close monitoring of CNI level. Conclusion
· Based on this experience, supportive treatment could be sufficient.
· Clinical examination supported by oxygen saturation and portable CXR rather than CT scan could be enough and limit the spread of infection.
· Short hospital stay with self-isolation on discharge reduces the burden on the health service and protect the staff and the public.
Level of evidence: 4 case series Impact factor of a journal
· Is a scientometric index that reflects the yearly mean number of citation of articles published in the last two years in a given journal provided by Clarivate web of science.
· Clarivate web of science provides researchers faculty and students with quick, powerful access to the word leading citation database.
I like your well-structured summary in great details, and conclusions. I appreciate level of evidence that you have allocated to this article on COVID19 virus in renal transplant.
Please summarise this article. Introduction; –The new coronavirus disease 2019 (COVID-19) infection emerged in Wuhan city, China, in December 2019.
-By April 26, 2020, infections related to coronavirus disease 2019 (COVID-19) affected people from 210 countries and caused 203,818 reported deaths worldwide.
-Among kidney transplant recipients, they have a high risk of infection due to long-term immunosuppression and associated comorbidities.
-There are few studies discussed the outcome of COVID-19 in kidney transplant recipients. Aim;
-Pretending experience in managing COVID-19 disease in renal transplant patients in the absence of strong evidence. Methodology;
-They report 8 cases of kidney transplant recipients infected with COVID-19 (median age = 48.5 years; range = 21–71 years), including 4 males and 4 females. The most frequently associated comorbidity was hypertension.
-The most common presenting features were fever and cough & the main radiological investigation was a portable chest X-ray.
-Other common features included lymphopenia, high C-reactive protein, and a very high ferritin level.
-Overall, 1 patient was managed as an outpatient, the remaining 7 required hospital admission, 1 of those admitted patients referred to the intensive therapy unit.
-Management included supportive treatment (intravenous fluid therapy, monitoring renal function, and symptomatic treatment with or without ward-based oxygen therapy depending on oxygen saturation) and discontinuation of the antiproliferative immunosuppressive drugs.
-Seven patients recovered and discharged home to self-isolate & one patient required intensive care treatment and mechanical ventilation.
-Supportive treatment could be sufficient for the management or to be tried first.
-They also found that short hospital stay with self-isolation on discharge reduces the burden on the health service and protect the staff and the public. Conclusion;
-The presentations of COVID-19 infected renal transplant patients were not different from the general population where fever and cough were the most frequent symptoms.
-Covid-19 infection in transplant patients did not behave differently from the general population, Because of the small sample size, we could not evaluate the effect of immunosuppression on the course of the disease, but at least it is not a detrimental effect.
-Based on our experience, supportive treatment could be sufficient or at least to be tried first. It is worth mentioning that the clinical examination supported by simple bedside measures such as oxygen saturation and portable CXR rather than CT scan could be enough and limit the spread of infection.
-Since remdisivir was approved for the treatment of COVID-19 and its interaction with CNI is yet unknown, we recommend treatment with remdisivir in a hospital setting where CNI drug level monitoring is available. What is the level of evidence provided by this article? -This article is Case Series and a Brief Review of Current Evidence with (LOE IV)What is meant by the impact factor of a journal? –Impact factor (I. F.) is commonly used to evaluate the relative importance of a journal within its field and to measure the frequency with which the “average article” in a journal has been cited in a particular time period. -Journal which publishes more review articles will get highest IFs. -The impact factor of a journal is calculated by dividing the number of current year citations to the source items published in that journal during the previous two years .
I like your well-structured detailed summary, and conclusions. I appreciate level of evidence that you have allocated to this article on COVID19 virus in renal transplant.
This report summarizes the clinical presentation, management, and outcome of 8 cases of post-kidney transplant covid 19 infections from a single center in the UK
Published in nephron with an Impact score of 3.26 for the year 2022/2023
we can see covid 19 pneumonia occurs between 1-6 months after transplantation with variable and nonspecific symptoms but fever and cough are the predominant clinical features with or without AKI, patient characteristics, and demography are summarized in table 1 and table 2 summarize the labs and CT images while tabe3 summarizes the treatment and outcome.
the average age at the time of infection was 48 years (younger, 4 males and 4 females with predominate clinical presentation of fever, and cough, two patients had AKI and only one required CVVH as a mode of RRT .nonspecific cx r finding from normal Typical viral infiltration, All patients at tacrolimus based IS with prednisolone and 7 patients were on MMF and the only case was on azathioprine
the most frequent presentation in this case series fever with cough, two cases have AKI and in one case was severe AKI that mandates initiation of CRRT in icu
the comorbid disease was found in 6 patients including HTN IN 4, TYPE 11 DM in one, and malignancy in one case while bronchial asthma with superadded aspergillosis in one case, most of the patients required hospital admission and received supportive care with IVF and other supportive care one case treated as OPD with self-isolation
MMF was kept on hold in all cases and continued on tacrolimus with steroids
All patients have lymphopenia with high CRP and high ferritin was found in 3 cases in this case series they don’t use IL 6 routine monitoring however most of the r
reports found a significant link between severe covid 19 infections in those with lymphopenia, high CRP, and high ferritin associated with ARDS and increased mortality rate, especially with high 1L6 level (a novel marker for the diagnosis of covid 19)
renal involvement in covid 19 infection was reported in many studies and it varies from AKI to glomerulonephritis (proteinuria, hematuria) , TMA
in this series, only two cases had AKI one recovered with hydration and supportive therapy, and one case of severe covid 19 on the background of ASTHMA and get superadded aspergillosis this patient had oliguric AKI requiring high convection CVVH In conclusion, covid 19 severity and outcome are similar to the general population, and supportive therapy with hydration and withholding the antimetabolites was found to be effective in managing covid 19 in post-kidney transplantation, use of antivirals like remdesivir- had 31% faster time to recovery in severe covid 19 compared to the placebo group in one study, while the convalescent plasma benefit was questionable, also the use of clinical assessment with o2 saturation, and portable CXR should be the first line work up that limit the covid19 transfer and better infection control, limit the use of conventional CT case by case
Limitation
Case series from a single center
What is the level of evidence provided by this article?
Level 4, case series
What is meant by the impact factor of a journal?
It’s used to assess the frequency of citations over 2 years, the Impact factor of nephron 2.6 for 2021-2022
I like your well-structured detailed summary. I appreciate level of evidence that you have allocated to this article on COVID19 virus in renal transplant.
I appreciate your listing of limitations of this article. Please use sub-headings, under the heading of ‘Summary’ to make easier to read your write-up. Please use bold or underline to highlight headings and sub-headings.
Please do not leave a gap between a full stop (or comma) and a preceding word, otherwise a new line may start for a full stop (or comma). I quote from your write-up, ” .nonspecific cx r finding from normal Typical viral infiltration, All.”
Please summarise this article Introduction
Covid 19 has genomic similarities to SARS-CoV and MERS-CoV.
Kidney transplant recipients are thought to have high risk of infections due to the use of immunosuppressive therapy and associated co-morbidities.
Cases
8 reported cases;
4 male and 4 female.
3 had transplant within 3 months.
1 managed as an outpatient
1 required ITU admission.
2 had AKI, with 1 requiring CVVH.
6 patients had co-morbidities(1 asthma, 4 HTN, 1 DM, 1 Cancer, 1 bronchial asthma and aspergillosis)
CXR done in 7, with 2 being normal.
Most common presentation was fever 5 and cough 5.
All patients had lymphopenia and high CRP levels
Only 3 patients were done ferritin levels which were found to be high.
All were discontinued anti-proliferative medications.
None received anti-virals.
Discussion.
Hypertensive and diabetic patients have a double risk of Covid 19 while COPD patients have a four fold risk.
Pathophysiology of renal injury is unclear with postulated theories of cytokine storm and direct virus injury to the kidney.
Continuous renal replacement therapy may play a role in management of AKI in Covid 19 by removal of the inflammatory cytokines.
Lymphopenia, high CRP and ferritin levels have been associated with ARDS and unfavourable outcomes.
Patients with mild infections can continue or reduce immunosuppression.
Severe infections stop anti-proliferative first.
Severe cases requiring mechanical ventilation can stop CNI and continue on steroids.
Conclusions
Covid 19 infections in the transplant population presents similar to general population.
Supportive treatment could be sufficient and should be tried first.
Short hospital stay with self isolation reduce the burden on health care.
What is the level of evidence provided by the article?
This is a case series report hence level IV.
What is meant by impact factor of a journal?
It is used as an indicator of the importance of a journal in its field where journal with high impact factors are considered more important.
It measures the frequency a journal has been cited in a particular period which is usually 2 years.
Usually the journal must have completed minimum 3 years after publication hence can’t be done in new journals.
I like your well-structured detailed summary. I appreciate level of evidence that you have allocated to this article on COVID19 virus in renal transplant.
Covid-19 is associated with diffuse lung damage, respiratory failure and increased mortality, and the data available in patients receiving kidney transplant is limited
The current study is presenting 8 kidney transplant recipients (4 males and 4 femalles) who developed covid 19 after transplantation.
Age of the patients was ranging between 21-71 years with median age of 48.5 years, 3 of them developed covid 19 within 3 months of transplantation and 5 after 1-year post transplantation.
All were on tacrolimus, MMF, prednisolone except one who was on tacrolimus, azathioprine, prednisolone
Observations
Patients most commonly presents initially by fever and cough
6 patients had comorbidities (HTN, DM, cancer, coinfection with aspirgillosis)
All the patients had lymphopenia
All patients had elevated CRP
3 patients had elevated serum ferritin
6 of 8 patients had abnormalities in CXR
6 of 8 patients were admitted to the general word (one of them was on O2 therapy), 1 patient to the ICU (need MV, was co-infected with aspirgillosis) and , and one received outpatient management
Therapy received
All patients received supportive therapy including circulatory and ventilator support
Antimetabolite was stopped for all patients
2 patients developed AKI and one received CRRT
No patient received antiviral therapy or toclizumab
Conclusion and recommendations
The use of portable CXR is usually sufficient to prevent the spread of infection and the use of CT is restricted to critically ill patients with normal or uncertain appearance of CXR
In mild covid with no O2 requirement either no or mild reduction of antimetabolite are suitable options.
In patients with covid infection requiring O2 it is recommended to stop antimetabolite and in cases on mechanical ventilation, reducing the dose of CNI may be warranted keeping steroids
Remdesivir is a good treatment option for hospitalized COVID-19 not on mechanical ventilation
No clear evidence to support the use of tocilizumab in treatment of COVID-19 in both transplant and non-transplant patients.
The use of convalescent plasma or the combination of and ritonavir/aritonavir was disappointing
I like your well-structured detailed summary. I appreciate level of evidence that you have allocated to this article on COVID19 virus in renal transplant.
The epidemic of COVID-19 which started in Wuhan City, China has already spread to over 200 countries by April 2020, with a mortality of over 200 thousand as of that time.
The long-term immunosuppressive state and the background comorbidity among CKD patients made most transplant physicians conclude that kidney transplant patients are at great risk of COVID-19 infection
This article presents a case series with the data of the participants as follows
Demography, clinical data, and findings
8 kidney post-transplant patients comprising of 4 males and 4 females with graft age range between 2-8 years to the time of publication
The median age is 48.5 years, ranging between 21-71years
Common comorbidities are HTN and DM
All of them are on Tacrolimus-based immunosuppression
The most common clinical presentations are fever, and cough with one patient each requiring RRT, ICU admission, and outpatient care
The most common imaging finding is bilateral patchy consolidation and all the patients had lymphopenia with elevated CRP. Ferritin level was high among three patients it was measured
As a form of treatment, antiproliferative medication was discontinued from 6 patients in the study, and oxygen therapy for those who needs it
All the patients were discharged, except one that was managed at home by self-isolating and removing antiproliferative drug
A major limitation of the study is the small sample size
Conclusion
The study concluded that, the clinical presentation of post-transplant patients with COVID-19 infection is not different from the general population and that those with mild symptoms can be managed at home by self-isolation, and medication adjustment, and this will reduce the burden of the strained medical facility and the personnel.
The level of evidence is 4
The impact factor is used to evaluate the importance of a journal within its field and to measure the rate at which an article in the journal is been cited.
It is usually calculated by the ratio between the number of citations received in that year for publications in that journal that were published in the two preceding years and the total number of “citable items” published in that journal during the two preceding years
For example the impact factor of a journal in 2021
IF = Citation in the years 2021
Publication in the year 2021 + Publication in the year 2019
Hi Dr Abiola,
I am afraid, I would not agree with your answer.
Correct answer of IF for 2021 is:
A = the number of times articles published in 2019 and 2020 were cited by indexed journals during 2021. B = the total number of “citable items” published in 2019 and 2020.
1.Please summarise this article.Outcomes of COVID-19 infection in renal transplant; evidence from case reports
Muhammed Ahmed ELhadedy et .al reported 8 cases of COVID-19 In transplant recipients at Sheffield Kidney institute.
They were four males and four females with different time line after transplantation
The initial presentation were fever and cough
Two patients developed AKI and one of the required RRT in form of CRRT
The most common laboratory abnormalities were lymphopenia and elevated CRP
Most patient had normal CXR examination
Seven patients were admitted to the hospital, and one was managed as outpatients with isolation measures
The hospital management was supportive; IV fluids, oxygen therapy, ant-ipyretics, and monitoring the renal ward. Anti-proliferative agents were held during the COVID-19 admission without evidence of acute rejection
Interestingly only one transplant recipient required invasive ventilation and ICU admission
Conclusion
They concluded that, presentation and management of COVID-19 in transplant population is largely similar to that of the general population. Simple measures such as CXR, monitoring, and oxygen therapy are effective therapeutic approach. Reduced hospital stay and isolation on discharge significantly decreases pressure on the public and health care system
2.What is the level of evidence provided by this article?
Case series, level IV
3.What is meant by the impact factor of a journal?
Impact factor is commonly used to evaluate the relative importance of a journal within its field and to measure the frequency with which the “average article” in a journal has been cited in a particular time period. Journal which publishes more review articles will get highest IFs. Journals with higher IFs believed to be more important than those with lower ones. According to Eugene Garfield “impact simply reflects the ability of the journals and editors to attract the best paper available.” Journal which publishes more review articles will get maximum IFs.
Impact factor can be calculated after completing the minimum of 3 years of publication; for that reason journal IF cannot be calculated for new journals. The journal with the highest IF is the one that published the most commonly cited articles over a 2-year period.
The impact factor can be influenced and biased (intentionally or otherwise) by many factors. Extension of the impact factor to the assessment of journal quality or individual authors is inappropriate. Extension of the impact factor to cross-discipline journal comparison is also inappropriate.
Introduction:
The new coronavirus disease 2019 (COVID-19) infection emerged in December 2019, resulting in a high mortality rate worldwide. However, the data on its effect on kidney transplant recipients are limited.
This study addressed the experience of COVID-19 infection in 8 KTRs (4 female and 4 male).
Case 1:
A young KTR , presented 3 months post-Tx mainly with fever and lethargy and no respiratory symptoms. Normal CXR and COVID-19 swab was positive. She had hypertension on treatment.. Case 2:
An old male KTR for hypertensive nephropathy (2016), his course complicated with colon cancer. He presented only with dry cough, CXR showed bilateral patchy infiltrate and his tested positive for COVID-19. Case 3:
KRT for DM transplanted 2015, presented with fever only and abnormal CXR
Case 4:
KTR, transplanted in 2017, presented with fever and dry cough only. She was tested positive for covid.
All above mentioned cases were treated with supportive measures and discontinuation of MMF. They had a full recovery and were discharged in few days with stable kidney function.
Case 5:
KTR presented 2 months post-Tx (Wagner granulomatosis) with productive cough only, CXR; clear and tested positive for COVID. He was managed with stopping MMF and home isolated.
Case 6:
KTR transplanted in 2005 for IgAN. He presented with fever and AKI. His CXR showed bilateral infiltrate, high inflammatory markers, tested positive for covid and he has staph. aureus sepsis. He was managed supportively with broad spectrum antibiotic, stopping MMF and was discharged after 7 days with improvement in graft function.
Case 7:
Female with bronchial asthma, presented 4 months post KT with dry cough, respiratory distress and AKI. She rewuired ICU admission for respiratory support (initially CPAP then MV). MMF was discontinues. She was treated with broad spectrum antibiotic and antifungal ( UIT, aspergillus BAL ). She required CVVH for sever AKI. The support (MV and CVVH) weaned later on and discharge after 7 days from ICU transfer with low GFR. Case 8:
KTR (2013) presented with productive cough and SOB. She required O2 for hypoxia, abnormal CXR. She was managed with stopping azathioprine and reducing Tacrolimus dose while increasing prednisolone dose. She did not require dialysis and weaned off O2.
Conclusion:
-The most common initial symptoms were fever and cough
-All patients had lymphopenia and high CRP, ferritin.
-CXR variable from clear, to picture of viral pneumonia.
-The management included supportive care and discontinuation of antiproliferative drugs.
-IL-6 is considered a novel biomarker for COVID-19 diagnosis associated with an increased risk of mortality.
-There is no clear evidence to support the role of IL-6 blocker (tocilizumab) in treatment of COVID-19 in both transplant and non-transplant population.
– Portable chest X-ray was considered to reduce the transmission of infection
– Generally, in mild infections, the usual practice is to continue or reduce the dose of immunosuppressive drugs. Suggestion to discontinuation of the antiproliferative drugs while monitoring the patients closely.
– As there is no clear guideline the treatment should be individualized based on the careful assessment of each patient.
– Remdesivir provided faster time to recovery and approved by FDA as treatment option.
Level of evidence: level 4 case series
Impact factor of a journal:
It is a measure of the frequency of the average article in a journal has been cited in a particular year. It is used to measure the importance or rank of a journal by calculating the times its articles are cited.
The calculation is based on a two-year period and involves dividing the number of times articles were cited by the number of articles that are citable.
6 patients had multiple comorbidities (4 HTN, 1 T2DM, 1 bronchial asthma & aspergillosis, & 1 a H/O cancer).
Studies reported that HTN & DM doubled risk of infection, while COPD patients have a 5-fold risk.
1 patient had a post-TX malignancy (Ca colon). Liang et al. reported that 1% of COVID-19 patients had a H/O malignancy ((higher than the prevalence of cancer in the overall Chinese population (0.29%)).
Fever was the most common symptom followed by cough. 2 large studies reported that 82–87% of patients had a fever, & 44 to 65.7% had cough.
2 patients had AKI; 1 of them required RRT (CVVH). Early studies reported a low incidence of AKI (3–9%) in COVID-19 infection.
All patients had lymphopenia & a high CRP. Guan et al. reported 83.2% of lymphopenia on admission. Other reports linked CRP to unfavourable outcomes (ARDS & death).
CXR was done in 7 patients. 5 of them had bilateral patchy consolidation, & 2 had clear lungs. The reported radiological data of COVID-19 infection focused on CT findings_ a practice with extra burden & infection hazard to radiology departments.
Antiproliferative drugs stopped in 6 patients.
None of the patients received specific antiviral drugs.
Generally, in mild infections, the usual practice is to continue or reduce the dose of IS drugs. The authors suggest (the study size cannot give firm recommendations) discontinuation of the antiproliferative drugs while monitoring the patients closely.
Conclusions
Regarding COVID-19 infection, TX patients in this study behaved similarly to the general population.
Due to limited sample size, it was not possible to assess the impact of immunosuppression on the progression of the disease, but at least it is not a negative impact.
Supportive treatment could be sufficient.
Instead of a CT scan, a clinical examination & bedside tools like O2 saturation & a portable CXR may be sufficient.
A brief hospital stay combined with self-isolation after discharge lightens the load on the health system & safeguards the public & personnel.
In a hospital setting where CNI medication level monitoring is available, remdisivir is recommended.
=========================== 2.What is the level of evidence provided by this article? Level V =========================== 3.What is meant by the impact factor of a journal?
The frequency with which a journal article has been mentioned in a particular year is labeled as its impact factor. By counting how frequently the article is cited, this measures the significance of the journal.
By dividing the number of times journal articles were cited by the total number of papers that were citable over a 2-year period, impact factor may be computed.
Calculation of 2010 Impact Factor (IF): A= the number of times articles published in 2008 & 2009 were cited by indexed journals during 2010. B= the total number of citable items published in 2008 & 2009 A/B= 2010 impact factor. References
University of Illinois. Measuring your impact: Impact factor, citation analysis, and other metrics: Journal impact factor. 2023.
coronavirus disease 2019 (COVID-19) affected people from 210 countries and caused 203,818 reported deaths worldwide this by April 26, 2020. In the UK, mortality cases exceeded 30,000 .
Due to long-term immunosuppression , kidney transplant recipients have a high risk of infections. DISCUSSION
This report, presenting 8 cases of COVID-19 infection in kidney transplant patients from Sheffield Kidney Institute, UK. The median age of patients was 48.5 years , including 4 males and 4 females.
Three patients had kidney transplantation within the last 3 months, and the rest were transplanted for more than a year.
initial symptoms :
fever (5 patients)
cough (5 patients).
All 8 patients were receiving prednisone and tacrolimus.
7 patients were receiving mycophenolate mofetil.
1 patient was receiving azathioprine
Two patients had AKI .
1 of them required continuous veno-venous hemofiltration
One patient was managed as an outpatient , 7 patients requiring hospital admission one of them need ICU and mechanical ventilation, Bronchoalveolar lavage of this patient confirmed aspergillosis for which she is receiving antifungal treatment .
One patient required ward-based oxygen therapy.
The other 6 patients received supportive therapy on the renal ward.
Antiproliferative immunosuppressive drugs were discontinued for all patients. Risk factors :
Immunosuppression.
Underlying CKD.
Associated comorbidities:
Hypertension and diabetes(douple risk)
Bronchial asthma and aspergillosis
COPD(5 fold risk) Pathological pictures
Blood results :
All patients had lymphopenia and high CRP.
Proteinuria(44%)haematuria(26.7%), and had high serum Creatine(14.1%).
Three patients had elevated serum ferritin, and 1 patient had high serum interleukin-6 (IL-6).
A portable chest X-ray was performed in 7 patients, clear in 2 of them, and the rest had a picture consistent with viral pneumonia. TRETMENT
Stop Antiproliferative drugs .
Oxygen therapy
Supportive management may required mechanical ventilation .
plasma – derived from the blood may needed in sever cases.
Lopinavir and ritonavir may used.
Remdesivir showed promising results. Conclusion
The presentations of COVID-19 infected renal transplant patients were not different from the general population .
Fever and cough were the most frequent symptoms.
Transplant patients did not behave differently from the general population as far as COVID-19 infection is concerned.
Because of the small sample size, we could not evaluate the effect of immunosuppression on the course of the disease, but at least it is not a detrimental effect.
Supportive treatment could be sufficient or at least to be tried first.
Clinical examination supported by simple bedside measures such as oxygen saturation and portable CXR rather than CT scan could be enough and limit the spread of infection.
Short hospital stay with self-isolation on discharge reduces the burden on the health service and protect the staff and the public.
Since remdisivir was approved for the treatment of COVID-19 and its interaction with CNI is yet unknown, we recommend treatment with remdisivir in a hospital setting where CNI drug level monitoring is available. What is the level of evidence provided by this article?
Level V. What is meant by the impact factor of a journalecipients: Case Series and a Brief Review of Current Evidence
Is measure of the frequency where average articlein a journal had been cited in certain year. Journal which publishes more review articles will get highest IFs.
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence.
COVID-19 is emerged on 2019 in Wuhan city, China, there is a concept between clinician that kidney transplant recipients have a high risk of infection due to long-term immunosuppression and associated comorbidities.
Herein, this case series report 8 cases of kidney transplant recipients infected with COVID-19 from Sheffield Kidney Institute, UK.
The demographic characteristic showed that the median age of patients was 48.5 years, were 4 males and 4 females, three patients had recent KTX less than 1 year, and the rest were transplanted for more than a year. The most common initial symptoms were fever and cough (5 patients). All 8 patients were receiving prednisone and tacrolimus, 7 patients were receiving Mycophenolate mofetil, and 1 patient was receiving azathioprine. One of them required RRT(low incidence of AKI) and have a role remove inflammatory cytokines .One treated as outpatient and others need hospitalization.
Regarding laboratory investigations shown high CRP , ferritin, IL-6 and lymphopenia in most of cases and has negative impact on the cases, suggested that higher serum ferritin is associated with ARDS development, also IL-6 levels can be associated with an increased risk of mortality and death.
Most of them recovered with only supportive treatment and discontinuation of the antiproliferative immunosuppressive drugs, only 1 patient needed oxygen therapy, and 1 required mechanical ventilation, but we should deal a case by case management, for example if our patient worsening we should be cautious to stop CNI and increasing steroid therapy with close monitoring of graft to avoid attack of rejection. Conclusion:
Post KTX recipient is on high risk for COVID-19 infection due to multiple co-morbidities and immunosuppreive status but we should treat every case according to its clinical state, isolation is important and discontinuation of the antiproliferative immunosuppressive drug is the quintessential of the management plan with supportive treatment. Level of evidence :Case series (IV). What is meant by the impact factor of a journal?
Impact factor (IF) is the average number of citations received per article published in a journal during the 2 preceding years which measures the importance or rank of the journal by calculating the number of times its articles are cited.
This article is surrounding COVID 19 infection in kidney transplant recipients. Fever, cough, and hypertension are the most common presenting features. Lab investigations mainly revealed lymphopenia, high CRP, and high ferritin level. This infection is especially important when it comes to kidney transplant recipients because of the high risk of infection that recipients have from the intense long term immunosuppression and associated comorbidities.
This report and conclusions are based on 8 COVID 19 cases in kidney Transplnt recipients from Sheffield Kidney Institute in the UK.
Discussion
Transplant recipients are at high risk of infection due to many reasons, the major of which include immunosuppression, underlying CKD, associated comorbidities, and underlying hypertension and diabetes. Malignancy is a possible consequence of transplant.Incidence of malignancy among COVID 19 patients is close to 1% according to the data mentioned in this study.
The given study found that there is a higher frequency of kidney disease among COVID 19 patients. These may present as hematuria, proteinuria, and high serum creatinine. The reason behind kidney disease in these patients could be attributed to a possible cytokine storm syndrome being induced by the virus. Direct renal injury is also possible. The kidney could very well be the target of the virus. Due to this, treatment would include continuous renal replacement therapy (RRT) because this would consistently flush out the inflammatory cytokines such as tumor necrosis factor – alpha, IL-6, and IL-1Beta. All of these cytokines are involved in renal injury, and RRT plays a role in preventing such injury.
Lab investigations revealed lymphopenia and high CRP levels in these patients. It is possible that there is a link between lymphopenia and ARDS. Low lymphocyte or WBC count could be an indicator of fatal outcome.
IL-6 is considered as a unique biomarker for COVID-19 infection. Increased levels of this marker is associated with high risk of mortality. However, the sensitivity and specificity of this marker is still under study.
In terms of imaging, chest X-ray is seen as the predominant investigation for this infection. Bilateral patchy consolidation is found in most affected patients, however, it is also possible for infected patients to have no classical changes. It is essential to remember that CT for all these patients can burden the radiology department and even lead to temporary unavailability of CT services since decontamination has to take place. A good solution for this would be to use portable X-ray machine instead. British Society of Thoracic Imaging has issued guidelines stating that CT is not to be used unless there is high suspicion with normal or uncertain appearance of CXR in seriously ill patients.
Treatment would include cessation of anti-proliferative drugs such as azathioprine and MMF while monitoring the patient closely in case of severe infection. Corticosteroid therapy can be continued, with cessation of CNIs in those patients requiring mechanical ventilation. Treatment has to be individualized for each patient, particularly in the absence of clear UK guidelines or recommendations for COVID-19 transplant recipients.
The article finally recommends remdisivir as treatment for COVID-19 infection in this cohort of patients. However, since its interaction with CNIs is yet unknown, it is better to administer this drug and monitor any changes in a hospital setting.
Conclusion
Among the COVID 19 patients in the study, the most common and frequent symptoms were fever and cough. The study found that transplant recipients do not behave differently when it comes to COVID 19 infection in comparison with the general population. Supportive treatment would be sufficient in most cases, and should be part of first line management. Self isolation on discharge can help greatly in reducing the burden on health care workers and the public.
Level of evidence
This is a narrative article, and thus level of evidence is 5.
Impact factor of journal
Impact factor is a measure of the frequency with which the average article in a journal has been cited in a given year. This measures the importance or rank of the journal by calculating the number of times its articles are cited.
Impact factor can be calculated based on a two year period, and involves dividing the number of times articles in the journal were cited by the number of articles that citable.
Reference
University of Illinois. Measuring your impact : Impact factor, citation analysis, and other metrics: Journal impact factor (IF). 2023.
Available form : https://researchguides.uic.edu/if/impact
Please summarise this article. Introduction
o Coronavirus disease 2019 (COVID-19) infection, emerged in Wuhan city, China, in December 2019, has close genomic structural similarities with the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused the SARS pandemic in 2003 and the middle east respiratory syndrome coronavirus (MERS-CoV) that caused (MERS) epidemic in 2012
o By April 26, 2020, infections related to COVID-19 affected people from 210 countries and caused 203,818 reported deaths worldwide
o Aim of the study: manage COVID-19 disease in renal transplant patients (8 cases of COVID-19 infection in kidney transplant patients from Sheffield Kidney Institute, UK)
Case Reports Patient 1: a 21-year-old female presented with fever but no respiratory symptoms. She is lethargic and generally unwell. Clinical examination was unremarkable, and the chest X-ray was clear. Urine and blood cultures were negative. A nasal and throat swab for COVID-19 tested positive. She is hypertensive. She was on prednisone, tacrolimus, and MMF. She was admitted and received supportive treatment. MMF was discontinued and discharged after 2 days with full recovery and stable kidney functions
Patient 2: a 71-year-old male with hypertensive nephropathy. His baseline Cr was 240–260 μmol/L. His immunosuppressive regimen included prednisolone, tacrolimus, and MMF. He presented 4 years after transplantation with a dry cough with no other symptoms but stable vital signs. Chest X-ray revealed a patchy bilateral consolidation. He was tested positive for COVID-19 nasal and throat swab. MMF discontinued and received supportive treatment. He was discharged 2 days later with stable kidney functions
Patient 3: a 50-year-old male with a history of Wegner’s granulomatosis. He presented two months after transplant with productive cough and was tested positive for SARS-CoV-2 RNA despite unremarkable clinical examination. The chest X-ray was clear, and kidney function tests were stable. His immunosuppressive drugs were prednisolone, tacrolimus, and MMF. The management included discontinuation of MMF, reduction of tacrolimus dose, and self-isolation at home
Patient 4: a 63-year-old male with a history of IgA. He is hypertensive. He presented 15 years latter with fever and AKI. The chest X-ray showed patchy bilateral consolidation, and SARS-CoV-2 RNA was positive. Blood culture was positive for staphylococcus aureus. CRP was 175 mg/L, and serum ferritin was 929 μg/L. His immunosuppressive regimen was prednisolone, tacrolimus, and MMF. The patient was admitted and received IV broad-spectrum antibiotics and paracetamol. We stopped MMF and increased the tacrolimus dose. Kidney function tests improved. The patient recovered and discharged home after 7 days
Patient 5: A 47-year-old female with bronchial asthma. She was maintained on prednisolon, tacrolimus, and MMF. She presented a few months later with dry cough and shortness of breath but no fever. Chest X-ray revealed bilateral middle and lower zone consolidation. Nose and throat viral swabs for COVID-19 were positive. Kidney function tests showed AKI, and mild proteinuria. Microbiology workup showed positive urine culture for E. coli and negative blood culture. Serum CRP on admission was 344 mg/L and ferritin 2684 μg/L, with leukocytosis and lymphopenia. She was tachypnoeic with a respiratory rate of 36, and the peripheral oxygen saturation was 80%, therefore admitted to the ITU for non-invasive ventilation. Her respiratory functions got worse, and she required intubation and invasive ventilation. Bronchoalveolar lavage showed moderate growth of aspergillus. She received broad-spectrum antibiotics and antifungals. No specific antiviral drugs were given. MMF was discontinued. Her kidney functions deteriorated, and she became anuric; therefore CVVH was commenced. After 14 days, she was weaned off mechanical ventilation and transferred from the ITU to the medical ward. Her kidney functions improved and CVVH stopped. She was discharged 7 days later
Patient 6: A 71-year-old female with type II diabetes. Her immunosuppressive therapy included prednisolone, tacrolimus, and MMF. She presented 5 years after transplant with only fever. Chest X-ray showed bilateral peripheral mid and lower zone consolidation. Nasal and throat swabs were positive for COVID-19 RNA. Kidney function tests showed no change from baseline, and microbiological tests were negative. Serum CRP was 19 mg/L, while serum ferritin was 1,835 μg/L. She was admitted to the medical ward for supportive treatment. MMF was discontinued and discharged after 4 days with full recovery
Patient 7: A 40-year-old female with hypertension. She is maintained on prednisolone, tacrolimus, and MMF. Three years after transplant, she presented with fever and dry cough. Nose and throat swabs for COVID-19 RNA were positive. Kidney function tests were stable and microbiological analyses were negative. She was admitted to the medical ward. MMF was discontinued and supportive treatment was initiated. Patient discharged after 4 days with full recover
Patient 8: A 38-year-old male with a failing kidney transplant from June 2013 presented with productive cough and shortness of breath for 2 days. He was maintained on prednisolone, tacrolimus, and azathioprine. On admission on March 20, he had tachypnoea and hypoxaemia with oxygen saturation of 89% on room air (improved to >96% on 4 L/min oxygen through a nasal cannula). Nasal and throat swabs were positive for COVID-19 RNA. Kidney function tests remained unchanged despite the high baseline Cr. Chest X-ray revealed bilateral infiltrates. Management included discontinuation of azathioprine, reduction of tacrolimus dose, and increase of prednisolone dose to 15 mg OD. He did not require any dialysis. Oxygen saturation recovered to >95% on room air, and the patient was discharged after 2 days
Discussion
o Eight cases of kidney transplant recipients infected with COVID-19 (median age = 48.5 years; range = 21–71 years), including 4 males and 4 females
o The most common initial symptoms were fever and cough
o The most frequently associated comorbidity was hypertension
o The main radiological investigation was a portable chest X-ray
o All patients had lymphopenia and high CRP
o Seven patients required hospital admission and only one patient managed as an outpatient
o Management included supportive treatment and discontinuation of the antiproliferative immunosuppressive drugs
o Currently, the US Food and Drug Administration investigates the efficacy of convalescent plasma as a treatment option for patients with severe COVID-19 infection
o Remdesivir (a broad-spectrum antiviral nucleotide prodrug) can be effective against MERS-CoV and SARSCoV infections
o The Adaptive COVID-19 Treatment Trial proved that remdesivir-treated patients had 31% faster time to recovery when compared to control
Conclusion
o The presentations of COVID-19 infected renal transplant patients is the same as in the general population (fever and cough were the most frequent symptoms)
o No evaluation of the effect of immunosuppression on the course of the disease in this case series as the sample size is small
o Supportive treatment could be sufficient or at least to be tried first
o Clinical examination supported by simple bedside measures such as oxygen saturation and portable CXR rather than CT scan, could be enough and limit the spread of infection
o Short hospital stay with self-isolation on discharge, reduces the burden on the health service and protect the staff and the public
o Remdisivir which was approved for the treatment of COVID-19 interacts with CNI (remdisivir should be restricted in a hospital setting where CNI drug level monitoring is available)
What is the level of evidence provided by this article?Level IV (case series)
What is meant by the impact factor of a journal?o The impact factor (IF) is frequently used as an indicator of the importance of a journal to its field and to measure the frequency with which the “average article” in a journal has been cited in a particular time period
o The IF of a journal is not associated to the factors like quality of peer review process and quality of content of the journal, but is a measure that reflects the average number of citations to articles published in journals, books, thesis, project reports, newspapers, conference/seminar proceedings, documents published in internet, notes, and any other approved documents
o Journal which publishes more review articles will get highest IFs
o Journals with higher IFs believed to be more important than those with lower ones
o Impact factor can be calculated after completing the minimum of 3 years of publication; for that reason journal IF cannot be calculated for new journals
o The journal with the highest IF is the one that published the most commonly cited articles over a 2-year period
o IFs are calculated each year by Thomson scientific for those journals that it indexes, and are published in Journal Citation Reports (For example, if a journal has an IF of 3 in 2008, then its papers published in 2006 and 2007 received three citations each on average in 2008)
o The IF of any journal is calculated by the following formula:
Year impactfactor =A/B A is the number of times articles published in the previous two years were cited by indexed journals during 2012 B is the total number of citable items like articles and reviews published by that journal in the previous two years Reference
1. Sharma M, Sarin A, Gupta P, Sachdeva S, Desai AV. Journal impact factor: its use, significance and limitations. World J Nucl Med. 2014 May;13(2):146. doi: 10.4103/1450-1147.139151. PMID: 25191134; PMCID: PMC4150161.
Covid-19 in Renal Transplant Recipients; Introduction Covid-19 virus is a new coronavirus disease in 2019 that emerged in China (December 2019).
8 cases were studied in the transplant recipients with covid-19 infection in Sheffield Kidney Institute, UK. The median age of patients was 48.5 years (21 to 71 years), including 4 males and 4 females. 3 patients had transplantation within the last 3 months, and the remaining transplanted for over 1 year. The initial symptoms were
Fever (5 patients).
Cough (5 patients).
A chest x-ray (1st line radiological tool for detection of covid-19) showed bilateral patchy consolidation in 5 patients.
Generally in the large studies they reported fever in 82-87%, while cough was 44 to 65.7%.
All 8 patients received prednisolone and tacrolimus, 7 received MMF and 1 received AZA. 2 patients develop AKI, (1 required CRRT). All patients had lymphopenia and high CRP. 3 patients had high ferritin and 1 patient had an elevated IL-6. A portable x-ray was clear of 2 of the patients and the rest had a picture of viral pneumonia. 1 managed as an outpatient and advised for home isolation, the others required hospital admissions, and 1 required ITU admission, where she need mechanical ventilation, with bronchoalveolar lavage show aspergillosis for which she received antifungal treatment. The remaining patients (1 need O2 ) and the other need supportive renal treatment, with or without O2 therapy. Anti-proliferative management D/C in all patients. Risk factors for infection in transplanted case;
Immunosuppressants.
Underline CKD.
Associated comorbidities.
HTN and DM had double risks of infection.
COPD had 5 fold risks for infection.
The fatal outcome associated with
Associated lymphopenia and leukopenia.
Higher CRP level.
Higher IL-6 level ( a novel biomarker of covid-19) and no clear evidence of using tocilizumab in treating covid-19 patients
6 patients had multiple comorbidities (HTN, T2DM, Bronchial asthma, and a history of cancer). Pathogenesis of AKI in covid-19 infection is unclear but it can be due to
Cytokines storm syndrome.
Direct renal viral injury.
Proteinuria 44%.
Hematuria 26.7%.
high serum Cr in 14%.
CRRT showed promising results in patients with SARS and MERS. Treatment
Treatment should be individualized.
In mild condition; D/C MMF.
In severe cases requiring MV stop CNIs and continue prednisolone.
Remdesivir; showed a promising results; It was found by one trial that it had a faster recovery time when compared to control.
Conclusion
Covid-19 infection in transplant patients, have the same presentation as general population.
And behave the same as the general population in hospitalized patients.
Supportive treatment should be the first line management.
Monitoring and follow up should based on clinical examination, O2 saturation and chest x-ray.
Remdesivir proved to be the treatment of hospitalized patientswith monitoring CNIs levels.
Level of evidence Level ((V)) The impact factor of the Journal Is the number of times articles of the journal published in the past 2 years have been cited in the JCR year. The impact factor is calculated by dividing the number of citations in the JCR year by the total number of articles published in the previous 2 years.
This study is a case series – Level of Evidence IV
Introduction
The spread of SARS CoV 2 quickly affected several countries and initially, there was little data. This study reports eight cases of kidney transplantation with COVID 19
Clinical cases
Patient 1 – Deceased donor to a 21-year-old woman with fever, respiratory symptoms, and normal chest X-ray. Tacrolimus 4mg + MMF 500mg + Prednisone 5mg.
MMF was suspended and discharged with stable renal function
Patient 2 – Male, 71 years old Tacrolimus 6.4 + MMF 500mg + Prednisone 5mg with pulmonary consolidations on chest X-ray. He discontinued MMF and was discharged two days later with normal renal function.
Patient 3 – 50-year-old male with recent living donor and cough. Normal X-rays and stable renal function using Tacrolimus 13.4 + MMF 1g + prednisone 5mg. He suspended mycophenolate and went home.
Patient 4 – Male, 63 years old, deceased donor. Fever and acute kidney injury with bilateral pulmonary consolidation. Tacrikunys 2.7 + MMF 1g + Prednisone 5mg. He increased the dose of tacrolimus and suspended the MMF with improvement in renal function, and he was discharged after seven days.
Patient 5 – a 47-year-old woman with a recent deceased donor with Tacrolimus 5-7 + MMF 500mg + Prednisone 5mg. He presented respiratory symptoms but without fever, with alteration in the X-rays and evolution with consolidations. Evolved with proteinuria and acute kidney injury. Elevated IL6. He presented worsening breathing patterns and intubation when MF was suspended. She improved her kidney function, was extubated, and discharged 21 days later.
Patient 6 – Female 71 years old deceased donor using tacrolimus + MMF + prednisone with fever and no other symptoms. X-rays with alteration and consolidation. There was no change in renal function and MMF was suspended with hospital discharge after four days
Patient 7 – 40-year-old female deceased donor using tacrolimus + MMF + Prednisone with fever and dry cough. Suspended MMF and discharged after four days.
Patient 8 – 38-year-old male with loss of renal function and productive cough. She uses Tacrolimus + Azathioprima and prednisone.
Discussion
Of these patients, only one had the need for hemodialysis again. Chest X-rays were normal in two cases and altered in the others. Only one patient required intubation, but he recovered his respiratory status and renal function. One of the patients evolved to CAPA (Post COVID Pulmonary Aspergillosis). All patients discontinued the antiproliferative.
Transplanted patients have more risks and comorbidities that favor more severe conditions. Five patients had fevers and five had coughs. Two patients had acute kidney injuries, one requiring dialysis.
All patients with lymphopenia and elevated protein C reacted. Serum ferritin and IL6 were measured in a few patients, but all had high values.
Despite the small number of cases, discontinuing antiproliferative drugs is highly recommended. Maintaining corticosteroid therapy is recommended.
Conclusion
Tomography seems to be the best diagnostic test. The use of Remdesivir looks promising, but its interaction with calcineurin inhibitors is unknown, so it is important to monitor the drug during its use.
Impact Factor is a method used to rank scientific journals based on the citations they receive. The calculation is made by adding the citations of articles received in the year of calculation of the impact factor and dividing this number by the number of articles published in the two years preceding this calculation.
COVID-19 has close genomic structural similarities to SARS-CoV and MERS-CoV, and has caused 203,818 reported deaths worldwide. 8 cases of kidney transplant recipients infected with COVID-19 due to long-term immunosuppression and comorbidities have been reported.
Case Reports
Patient 1
Had a deceased donor kidney transplant in December 2019 and presented with a high fever and no respiratory symptoms.
A nasal and throat swab for COVID-19 tested positive and she was on prednisone, tacrolimus, and mycophe-nolate mofetil.
Patient 2
A 71-year-old male with hypertensive nephropathy had a history of colon adenocarcinoma and was on immunosuppressive medications, but was tested positive for COV-ID-19.
Patients 3, 4, and 5 received live donor kidney transplants in February 2020, February 2019, and December 2019 respectively.
Patient 3 was test-ed positive for SARS-CoV-2 RNA despite unremarkable clinical examination, and his immunosuppressive drugs were prednisolone 5 mg OD, tacrolimus (trough level was 13.4 ng/mL), and MMF 500mg BD.
He was advised to drink plenty of fluids and report to the unit any new symptoms.
Patient 4 was a 63-year-old male with a history of IgA nephropathy with a deceased donor kidney transplant in December 2005.
He was admitted and received IV broad-spectrum antibiotics and paracetamol.
Patient 6:
A 71-year-old female with type II diabetes received de-ceased donor kidney transplantation in November 2015.
Her kidney functions deteriorated and continuous veno-venous hae-modiafiltration (CVVH) was commenced.
On April 2, she presented with fever (38.5°C) and no other complaint. Chest X-ray showed bilateral peripheral mid and lower zone consolidation.
Nasal and throat swabs were positive for COVID-19 RNA. Kidney function tests showed no change from baseline, and microbiological tests were negative.
She was admitted to the medical ward for adequate hydration and symptomatic treat-ment.
Patient 5 received a deceased donor kidney transplant in December 2019 and presented on April 6 with dry cough and shortness of breath.
Chest X-ray showed bilateral middle and lower zone consolidation, and SARS-CoV-2 RNA was positive.
Kidney function tests showed AKI, mild proteinuria, and leu-kocytosis. Microbiology workup showed positive urine culture for E.coli and negative blood culture.
Patient 6 was a 71-year-old female with type II diabetes who received a deceased donor kidney transplantation in November 2015.
On admission, her serum CRP was 344 mg/L and ferritin 2684 μg/L, with leu-kocytosis, lymphopenia, and interleukin-6.
Bronchoalveolar lavage showed moderate growth of aspergillus, and she received broad-spec-trum antibiotics and antifungals. Her kidney functions deteriorated, and continuous veno-venous hae-modiafiltration (CVVH) was commenced.
After 14 days, she was weaned off mechanical ventilation and transferred from the ITU to the medical ward.
Kidney function tests showed no change from baseline, and microbiological tests were negative.
Patient 4 was a 63-year-old male with a history of IgA nephropathy with a deceased donor kidney transplant in December 2005.
His immunosuppressive drugs were prednisolone 5 mg OD, tacrolimus (trough level was 13.4 ng/mL), and MMF 500mg BD. He presented on March 20 with fever and acute kidney in-jury (AKI).
Chest X-ray showed patchy bilateral consolidation, and SARS-CoV-2 RNA was positive.
He was admitted and received IV broad-spectrum antibiotics and paracetamol.
Kidney function tests improved (serum Cr de-creased to 113 μmol/L). He recovered and discharged home after 7 days.
Patient 6 was a 71-year-old female with type II diabetes who received de-ceased donor kidney transplantation in November 2015.
On April 2, she presented with fever (38.5°C) and no other complaint.
Chest X-ray showed bilateral peripheral mid and lower zone consolidation.
Kidney function tests showed no change from baseline, and microbiological tests were negative.
MMF was discontinued and discharged after 4 days with full recovery.
This report presents 8 cases of COVID-19 infection in kidney transplant patients from Sheffield Kidney Institute, UK.
The median age of the patients was 48.5 years and the most common initial symptoms were fever (5 patients) and cough (5 patients).
All 8 patients were receiving prednisone and tacrolimus, 7 patients were receiving mycophenolate mofetil, and 1 patient was receiving azathioprine.
Blood results showed that all patients had lymphopenia and high CRP.
A portable chest X-ray was performed in 7 patients, which was clear in 2 of them, and the rest had a picture consistent with viral pneumonia.
One patient required ITU admission, one patient required mechanical ventilation, and one patient required ward-based oxygen therapy.
Antiproliferative immunosuppressive drugs were discontinued for all patients due to multiple risk factors, including immunosuppression, underlying CKD, and associated comorbidities.
Lianget al. [11] reported that 1% of COVID-19 patients had a history of malignancy, which was higher than the preva-lence of cancer in the overall Chinese population (0.29%).
The most frequent tumour was lung cancer, and the most frequent presentation was fever (5 patients) and cough (5 patients).
Two large studies demonstrated that 82-87% of their patients had a fever, while patients with cough ranged from 44 to 65.
Two of our patients had AKI, and the pathophysiology of renal involvement is still unclear, but theories suggest a cytokine storm syndrome or direct renal injury by the virus.
Scientists succeeded in isolating SARS-CoV-2 from a urine sample of an infected patient.
COVID-19 infection is associated with high CRP and lymphopenia, which can lead to adverse outcomes such as ARDS development, myocardial damage, and death.
Continuous renal replacement therapy may play a role in the management of AKI in COVID-19 patients.
Serum ferritin is an acute-phase protein, but its sensitivity and specificity are unknown.
IL-6 is considered a novel biomarker for COVID-19 diagnosis, but it is not routinely measured and there is no clear evidence to support the role of IL-6 blocker (tocilizumab) in treatment.
Chest X-ray was used as a first-line triage tool, but CT decontamination may disrupt service availability and portable chest X-ray should be considered to reduce transmission.
CT is not recommended unless there is high suspicion of CXR in a seriously ill patient, and it is important to be familiar with the radiological findings of COVID-19 on chest X-ray.
When managing immunosuppression in kidney transplant recipients, the age, severity of infection, post-trans-plant duration, any other associated comorbidity, tissue mismatch, and any episodes of rejection should be considered.
The treatment should be individualized based on the careful assessment of each patient.
The US Food and Drug Administration has authorized the use of remdesivir as a treatment option for hospitalized COVID-19 patients.
The presentations of COVID-19-infected renal transplant patients were similar to the general population, with fever and cough being the most frequent symptoms.
Supportive treatment could be sufficient, and short hospital stay with self-isolation on discharge reduces the burden on the health service and protects the public.
Treatment with remdisivir should be done in a hospital setting with CNI drug level monitoring.
==================================================================== What is the level of evidence provided by this article?
The level evidance is IV
================================================================== What is meant by the impact factor of a journal?
–
The impact factor (IF) is a measure that reflects the average number of citations to articles published in journals, books, thesis, project reports, newspapers, conference/seminar proceedings, documents published in internet, notes, and any other approved documents.
It is used to evaluate the relative importance of a journal within its field and to measure the frequency with which the “average article” in a journal has been cited in a particular time period.
Journals with higher IFs are believed to be more important than those with lower ones. Journal which publishes more review articles will get maximum IFs.
Impact factor (IF) is the average number of citations receivedper article published in a journal during the 2 preceding years.
For example, if a journal has an IF of 3 in 2008, then its papers published in 2006 and 2007 received three citations each on average in 2008.
The IF of any journal may be calculated by the formula;2012 impactfactor =A/BWhere A is the number of times articles published in 2010 and 2011 were cited by indexed journals during 2012.
In an ideal world, evaluators would read each article and make personal judgments.
Sharma M, Sarin A, Gupta P, Sachdeva S, Desai AV. Journal impact factor: its use, significance and limitations. World J Nucl Med. 2014;13(2):146. doi:10.4103/1450-1147.139151
Garfield E. The history and meaning of the journal impact factor. JAMA. 2006;295:90–3.
Introduction:
The new coronavirus disease 2019 (COVID-19) infection, emerged in Wuhan city, China, in December 2019.
COVID-19 has close genomic similarities to SARS-CoV and MERS-CoV, causing 203,818 reported deaths worldwide.
COVID-19 in kidney transplant recipients has a high risk of infection due to immunosuppression and comorbidities.
This article presents an 8 case series with review of COVID-19 virus infection, 7 of them received tacrolimus+MMF+ prednisolone, with different comorbidities.
Two of them experienced AKI, most had lymphopenia with two with profound lymphopenia.
Discussion:
Median age in these 8 cases is 48.5 years.
The most common initial symptoms were fever and cough.
Blood results showed lymphopenia, high CRP, elevated ferritin, IL-6, and a portable chest X-ray (normal in two of patients), with 6 patients with pneumonia.
Antiproliferative immunosuppressive drugs were discontinued for all patients.
Transplant patients are at a high risk of infection due to multiple risk factors, including immunosuppression, CKD, and comorbidities, such as hypertension and diabetes.
Lianget al. reported that 1% of COVID-19 patients had a history of malignancy, higher than the overall Chinese population.
The incidence of AKI in COVID-19 patients is low, but recent studies have shown a higher frequency of renal abnormalities, suggesting a cytokine storm syndrome or direct renal injury. Continuous renal replacement therapy may play a role in the management of AKI.
COVID-19 infection is associated with high CRP levels, which can lead to adverse outcomes such as ARDS development, myocardial damage, and death. Serum ferritin is an acute-phaseprotein, but its sensitivity and specificity are unknown.
IL-6 is a novel biomarker for COVID-19 diagnosis, but its sensitivity and specificity are unknown, and there is no clear evidence of its use in treatment.
CT decontamination may disrupt radiology service availability, so portable chest X-ray should be considered to reduce transmission of infection. CT should not be used unless there is high suspicion of CXRin a seriously ill patient.
The small sample size of this study cannot give firm recommendations, but suggests discontinuation of antiproliferative drugs while monitoring the patients closely in cases of severe infection. Treatment should be individualized based on individual assessment of each patient.
The US Food and Drug Administration has authorized the use of remdesivir as a treatment option for hospitalized COVID-19 patients due to its promising results.
Conclusion:
The presentations of COVID-19-infected renal transplant patients were similar to the general population, with fever and cough being the most frequent symptoms. Supportive treatment should be tried first, and short hospital stay with self-isolation on discharge reduces the burden on the health service and protects the public.
What is the level of evidence provided by this article?
Level of evidence IV – case series.
What is meant by the impact factor of a journal?
Impact factor = average article cited x specific time period (previous two years).
IF 2023 = articles cited in 2021&2022 divided by total articles published in 2021&2022.
it measures the frequency with which the “average article” in a journal has been cited in a particular time period. Journal which publishes more review articles will get highest IFs.
The novel COVID-19 infection, which arose in Wuhan, China, in December 2019, has genetic structural similarities with the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused the 2003 SARS pandemic and the 2012 MERS pandemic. COVID-19 infected 210 nations and killed 203,818 persons till April 26, 2020.
Discussion:
Immunosuppression, CKD, and comorbidities such as hypertension and diabetes put transplant patients at risk of infection. Four had hypertension, one had type II DM, one had bronchial asthma and aspergillosis, and one had malignancy. Numerous COVID-19 research studies examined similar comorbidities. These investigations found that hypertensive, diabetic, and COPD patients had double- and five-fold infection risks, respectively.
All patients exhibited lymphopenia and elevated CRP. Guan et al. found lymphopenia in 83.2% of infected patients on admission. Another study linked lymphopenia to ARDS. Two other studies found that patients with low lymphocyte/white blood cell ratios on entry and after hospitalization died.
Several studies linked COVID-19 to elevated CRP. found that 60.7% of patients had increased CRP, with severe cases having higher levels than non-severe ones.
6 patients discontinued their antiproliferative medicines and underwent supportive care; 1 needed oxygen therapy and one needed mechanical breathing. No patients got particular antiviral medications. COVID-19 in renal transplant patients should consider age, degree of infection, post-transplant length, comorbidities, tissue mismatch, and rejection events while administering immunosuppression. With minor infections, immunosuppressive medications are usually continued or reduced.
Conclusion
Fever and cough were the most common symptoms in COVID-19-infected kidney transplant patients. The COVID-19 infection in our transplant patients was similar to the overall population. We couldn’t assess immunosuppression’s impact on disease progression due to the limited sample size, but it didn’t hurt. Based on our expertise, supportive therapy may suffice or be attempted initially. Clinical evaluation backed by bedside measurements like oxygen saturation and portable CXR rather than a CT scan may be adequate to minimize infection.
Level of evidence: IV
IF: the factor of influence It is usual practice to utilize the impact factor (IF) of a journal in order to quantify the frequency with which the article in the journal has been referenced in a certain amount of time and to evaluate the relative relevance of a journal within its own discipline. Journals that publish a greater number of review papers will have higher impact factors.
–Summary Introduction
COVID19 virus that appeared in China December 2019 had genotypic features similar to SARS which caused SARS pandemic 2003 and MERS epidemic 2012.
COVID lead to 203,818 reported deaths all over the world.
Renal transplant recipients on long term immunosuppressives are at greater risk of infections.
This is a case report of 8 kidney transplant recipient cases infected with COVID-19.
This case report included 4 males and 4 females. Most cases had hypertension as a comorbidity, manifesting with fever and cough.Portable chest X-ray was done for the cases.
Most cases lab showed lymphopenia, high C-reactive protein, and extremely elevated ferritin level.
1 case was treated on outpatient bases ,the other 7 cases required hospital admission, and 1 needed ICU admission and mechanical ventilation ,BAL was done confirming aspergillosis and antifungal therapy was given
Management was mainly supportive treatment as intravenous fluid therapy, following kidney function oxygen therapy as needed and antiproliferative immunosuppressives were stopped.
The 7 cases were recovered and were sent for home isolation.
Home isolation was the best option to decrease burden on hospitals and to limit spread of infection. Discussion
Transplant recipients are at a high risk of infection because of immunosuppression, CKD, and associated comorbidities particularly hypertension and diabetes.
Studies demonstrated that hypertension and diabetes have a double-fold infection risk and COPD patients have a 5-fold higher risk.
1 case had post transplant malignancy which was adenocarcinoma of sigmoid colon in concordance with Liang et al stating that COVID-19 patients had a
higher malignancy history compared to cancer prevalence in the overall Chinese population and the most common malignancy was cancer lung.
The mechanism of renal involvement is not clarified yet, but cytokine storm syndrome or direct renal injury by the virus were suggested.
CRRT revealed favourable outcomes in treatment of AKI associated with SARS and MERS.
It was suggested that inflammatory cytokines can be eliminated by high-volume hemofiltration.
Another study shed light on the possibility of a connection between lymphopenia and ARDS occurrence.
It was demonstrated that low lymphocyte/WBCs ratio had fatal outcomes.
The current study mentioned that high CRP and ferritin can be associated with poor prognosis .
Elevated IL6 level is accompanied with high mortality risk.
The British Society of Thoracic Imaging (BSTI) guidelines stated that CT is not recommended except if COVID is highly suspicious with normal or uncertain appearance of CXR in severely ill cases.
When manipulating immunosuppressives in such cases many aspects have to be considered as comorbidities ,age ,infection degree and rejection attacks.
For cases with mild infections, the immunosuppressives can be continued or reduced .
It is advised to stop antiproliferative drugs with close follow up in severe infection.
While for critically ill cases in need of ventilation ,CNI discontinuation is debatable and steroids can be continued.
Remdesivir is effective against MERS-CoV and SARSCoV infections with favourable outcomes.
FDA authorised Remdesivir use for hospitalised COVID patients. Conclusion
Covid infected renal transplant recipients were similar to general population.
–Level of evidence is 4 because it is a case report
–Impact factor is a measure of the frequency where the average article in a journal had been cited in a certain year. It is used to measure the importance or rank of a journal by calculating the times its articles are cited.
1- New COVID19 corona viruses has multiple presenting pictures in the patients especially immunosuppressed patients.
2- It is structurally similar to SARS-COV, and MERS-CO viral infection.
3- Can presented by fever which is important symptom, dry cough.
4- CXR may be clear or revealed consolidating patch or infiltration.
5- So, and clinical suspicion for COVID19, nasopharyngeal swab and PCR should be done to confirm or exclude the diagnosis.
6- Management includes general supportive measures like hospitalization, hydration, lab investigations.
7- As regard immunosuppressive medications; MMF should be reduced or discontinued, same dose CNI and steroid.
8- CNI should be reduced in severely ill patients
9- Convalescent plasma – derived from the blood of recovered patients could be used as a treatment option in severe cases.
10- Remdesivir is antiviral drug used to enhance recovery in hospitalized patients
level 4 of evidence
impact factor IF of journal is commonly used to evaluate the relative importance of a journal within its field and to measure the frequency with which the “average article” in a journal has been cited in a particular time period. Journal which publishes more review articles will get highest IFs.
Please summarise this article.case series for 8 cases of kidney transplant recipients infected with COVID-19
submitted earlier in the pandemic : June 17, 2020 which was cited 28 times (per google scholar) – checked 18 March 23. Authors reported their experience with 8 cases from preesntation, investigationsa and CXR. The treatment was supportive while holdling antimetabolites.
What is the level of evidence provided by this article? Level IV according to Oxford system For Evidence Levels:
What is meant by the impact factor of a journal?it is the frequency of citation of the average article in a particular year. It measures the rank of a journal by calculating the times of citations.
It’s calculated number of citations/number of articles – in the 2 years previous to the year of calculation.
COVID-19 infection had similar genomic structure to SARS-CoV & MERS-CoV.
It cause 203,818 deaths in April 2020.
SOT recipients have are high risk for COVID-19 due to long term use of immunosuppression.
Cases:
8 KTR from different age group
Clinical features range from mils symptoms (treated at home) to severe manifestation & ICU admission & intubation & need of CRRT.
COVID-19 PCR were positive
Some case complicated by bacterial or fungal infection.
Anti-proliferative stopped in all patients.
All patients recovered & discharged to home.
Discussion:
KRT are at increased risk of infection due to use of immunosuppression, CKD & associated co-morbidities(TH,DM).
HT & DM associated with double fold of risk of infection & COPD increase risk 5 folds.
COVID-19 risk increased in patients with malignancy.
Most common presenting symptoms are fever & cough.
COVID-19 increase risk of AKI which may be result of cytokine storm syndrome or direct renal injury by virus.
CRRT had a role in AKI treatment caused by COVID-19.
Lymphopenia & high CRP noticed more among in severe case compared to non severe cases.
High CRP & ferritin linked to poor outcome(ARDS, myocardial damage & each).
Increased IL-6 can be associated with increased mortality, but there was no documented role of IL-6 blocker in COVID-19 patients.
CXR is the first imaging modality used during COVID-19 assessment, & CT chest used for high suspicion with normal CXR.
Immunosuppression modification should be individualized according assessment of each patient.
Convalescent plasma investigated as treatment option for severe COVID-19.
FDA authorize use of remdesivir as treatment for hospitalized sever cases.
Level of evidence is 5
Impact factor:
Is the measurement of journal citation frequency in a particular year, it calculated based on 2 year period & dividing number of articles citing by number of articles that are citable.
1. Please summarise this article.
This trail has demonstrated the management of post-transplant recipient infected with COVID.
The most common feature presenting feature was fever, cough and other constitutional symptoms,
Laboratories shows high CRP, lymphonia, and high ferritin level.
The management strategy was general management, discontinuation of immunosuppression, there other treatment option, dexamethasone, tocilizumab, baricitinib and casirivimab and imdevimab.
2. What is the level of evidence provided by this article?
Level of evidence IV
3. What is meant by the impact factor of a journal?
Impact factor demonstrated that how the article was cited.
This is a serial case reports of 8 patients . all of them are kidney transplant recipients who acquired COVID19 infection.COVID19 in transplanted patients has the same symptoms in form of fever and cough. So far no observed effects of IS was observed on the course of the disease. The saple size was small . management is mainly supportive . diagnosis is through CXRay. Remdesivir is recommended for treating cases.
Level of evidence is 4 as it is a case series
The impact factor is the number of citation within the last 2 years
Summary of the article
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
Introduction:
The new coronavirus (COVID-19) pandemic emerged in December 2019, was highly infectious killing millions of people across globe. There is a common belief that, kidney transplant recipients have higher risk of infection due impact of immunosuppression and associated comorbidities. Course and outcomes of 8 kidney transplant recipients infected with COVID-19 are discussed here.
The common features of COVID-19 in KTR:
1. Fever and cough – most common presentation.
2. Lymphopenia, high CRP and ferritin level.
3. HTN – most common co-morbidity.
4. 2 patients had AKI – 1 of them had rising Creatinine, required CVVH.
Therapeutic strategies for managing the KTRs with COVID-19 infection:
1. IS reduction – antiproliferative (MMF) discontinued for all.
2. Managed on outpatient basis; 1 patient advised self-isolation at home.
3. Hospital admission to Renal Ward, supportive treatment (IV fluid, monitoring vitals, saturation, RFT, and symptomatic treatment with or without oxygen supplement, based on PaO2) – 6 patients.
4. ICU admission, mechanical ventilation and CVVH – 1 patient.
Discussion:
1. Early studies reported – low incidence of AKI (3–9%).
2. Recent study by Cheng et al, showed a higher frequency of renal abnormalities among 710 patients –
· 44% had proteinuria.
· 26.7% had haematuria.
· 14.1% had high serum Cr.
3. The pathophysiology of renal involvement is still unclear, but theories suggested are cytokine storm syndrome and direct renal injury by the virus.
4. Diagnosis and laboratory features of COVID-19 infection:
· Low lymphocyte / white blood cell ratio had fatal outcomes.
· High CRP (60.7%) is linked to unfavourable outcome – ARDS, myocardial damage and death.
· Higher serum ferritin is associated with ARDS development and death.
· High IL-6 levels (52%) – novel biomarker, a/w increased risk of mortality in COVID-19
Imaging:
CXR – may show patchy consolidation; HRCT chest to be done when there is high clinical suspicion, with CXR normal / uncertain features in seriously ill patient.
5. Management of COVID-19 infection:
A. Mild infections: the usual practice is to reduce immunosuppression – withhold antiproliferative suggested.
B. Severe infection with requirement to mechanical ventilation: to maintain corticosteroids, hold antiproliferative and to argue about ceasing CNIs.
C. Remdesivir-treated patients had 31% faster time to recovery when compared to control.
D. CRRT may play a role in the management of AKI in COVID-19 patients. It was assumed that high-volume hemofiltration could remove inflammatory cytokines (tumour necrosis factor, IL-6, and IL-1β) involved in the pathogenesis of renal injury.
Level of evidence provided by this article:
case series – level of evidence grade 5.
The impact factor of a journal:
Journal impact factor (JIF) is sciento-metric index calculated by Clarivate, that reflects annual average number of citations of articles published in last 2years. indexed by Clarivate’s Web of Science.
Limitations of the JIF
· Some journals increase impact factor by reducing the number of scholarly records.
· Extension of the impact factor to the assessment of journal quality or individual authors is inappropriate.
· Extension of the impact factor to cross-discipline journal comparison is also inappropriate.
· Those who choose to use the impact factor as a comparative tool should be aware of the nature and premise of its derivation and also of its inherent flaws and practical limitations.
Dear All
You have noticed that I published this article before the publication of the results of the RECOVERY trial. Do you think I would have treated these patients differently?
Dear Prof. Ahmad:
You have noticed that I published this article before the publication of the results of the RECOVERY trial. Do you think I would have treated these patients differently?
“No”
for 7 of 8 patient – (mild to moderate illness) : general supportive care was only treatment required; 1 patient was managed even as outpatient.
However, 1 patient with severe illness (Cytokine storm Syndrome), required ICU admission, ventilatory support, CVVH. Only this patient would have been treated according to the Recovery Trial regimen (i.e IV dexamethasone 6 mg daily till recovery +/- Tocilizumab) should it be published that time.
RECOVERY trial used 4 therapeutic options – dexamethasone, tocilizumab, baricitinib and casirivimab-imdevimab can be used in critically ill COVID patients.
Only case 5 having high Serum IL-6, might have been benefitted from Tocilizumab + Dexamethasone, with good cover of antifungal and antimicrobial therapy.
Please summarise this article.
This short series demonstrates experience in managing COVID-19 disease in renal transplant patients in the absence of strong evidence.
The most frequently associated comorbidity was hypertension.
The most common presenting features were fever and cough.
The main radiological investigation was a portable chest X-ray.
Other common features included lymphopenia, high C-reactive protein, and a very high ferritin level.
Management included supportive treatment (intravenous fluid therapy, monitoring renal function, and symptomatic treatment with or without ward-based oxygen therapy depending on oxygen saturation) and discontinuation of the antiproliferative immunosuppressive drugs.
Supportive treatment could be sufficient for the management or to be tried first.
Introduction
In the UK, mortality cases exceeded 30,000 so far. There is a common belief among transplant clinicians that kidney transplant recipients have a high risk of infection due to long-term immunosuppression and associated comorbidities. Data, clinical picture, and outcomes of COVID-19 in kidney transplant recipients are scarce.
Discussion
Many studies showed that COVID-19 infection is associated with high CRP. Guan et al. reported that 60.7% of patients had an elevated CRP, while severe cases had a higher level compared to the non-severe ones (81.5 vs. 56.4% for CRP).
Other reports noticed that high CRP could be linked to unfavourable outcomes, such as ARDS development ,myocardial damage ,and death .
Serum ferritin was measured in only 3 of our patients, and the level was very high. Many reports suggested that higher serum ferritin is associated with ARDS development and death .Ferritin is an acute-phase protein, but we are not sure about the sensitivity and specificity concerning the outcome.
IL-6 is considered a novel biomarker for COVID-19 diagnosis.
Other studies suggested that increased IL-6 levels can be associated with an increased risk of mortality.
there is no clear evidence to support the role of IL-6 blocker (tocilizumab) in treatment of COVID-19 in both transplant and non-transplant population.
The British Society of Thoracic Imaging (BSTI) issued guidelines which state that there is no recommended use of CT unless there is high suspicion with normal or uncertain appearance of CXR in a seriously ill patient .
It is also essential for clinicians of all specialities to be familiar with the radiological findings of COVID-19 on chest X-ray.
Generally speaking, in mild infections, the usual practice is to continue or reduce the dose of immunosuppressive drugs.
we suggest discontinuation of the antiproliferative drugs (azathioprine and mycophenolate mofetil) while monitoring the patients closely.
Remdesivir was used as a compassionate treatment that showed promising results .
Besides, the Adaptive COVID-19 Treatment Trial (NCT04280705) proved that remdesivir-treated patients had 31% faster time to recovery when compared to control .
Based on the previous results, the US Food and Drug Administration has authorized the use of remdesivir as a treatment option for hospitalized COVID-19 patients .
Conclusion
In the above report, the presentations of COVID-19 infected renal transplant patients were not different from the general population where fever and cough were the most frequent symptoms. We believe that our transplant patients did not behave differently from the general population as far as COVID-19 infection is concerned. Because of the small sample size, we could not evaluate the effect of immunosuppression on the course of the disease, but at least it is not a detrimental effect. Based on our experience, supportive treatment could be sufficient or at least to be tried first. It is worth mentioning that the clinical examination supported by simple bedside measures such as oxygen saturation and portable CXR rather than CT scan could be enough and limit the spread of infection. We also found that short hospital stay with self-isolation on discharge reduces the burden on the health service and protect the staff and the public. Since remdisivir was approved for the treatment of COVID-19 and its interaction with CNI is yet unknown, we recommend treatment with remdisivir in a hospital setting where CNI drug level monitoring is available.
What is the level of evidence provided by this article?Level IV
What is meant by the impact factor of a journal?
used to measure the frequency with which the “average article” in a journal has been cited in a particular time period, which in turn reflect the potency & importance of the journal.
calculated based on a two-year period via dividing the number of citations by the number of citable articles.
Summary of the article
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
Introduction:
The new coronavirus (COVID-19) pandemic emerged in December 2019, was highly infectious killing millions of people across globe. There is a common belief that, kidney transplant recipients have higher risk of infection due impact of immunosuppression and associated comorbidities. Course and outcomes of 8 kidney transplant recipients infected with COVID-19 are discussed here.
The common features of COVID-19 in KTR:
1. Fever and cough – most common presentation.
2. Lymphopenia, high CRP and ferritin level.
3. HTN – most common co-morbidity.
4. 2 patients had AKI – 1 of them had rising Creatinine, required CVVH.
Therapeutic strategies for managing the KTRs with COVID-19 infection:
1. IS reduction – antiproliferative (MMF) discontinued for all.
2. Managed on outpatient basis; 1 patient advised self-isolation at home.
3. Hospital admission to Renal Ward, supportive treatment (IV fluid, monitoring vitals, saturation, RFT, and symptomatic treatment with or without oxygen supplement, based on PaO2) – 6 patients.
4. ICU admission, mechanical ventilation and CVVH – 1 patient.
Discussion:
1. Early studies reported – low incidence of AKI (3–9%).
2. Recent study by Cheng et al, showed a higher frequency of renal abnormalities among 710 patients –
· 44% had proteinuria.
· 26.7% had haematuria.
· 14.1% had high serum Cr.
3. The pathophysiology of renal involvement is still unclear, but theories suggested are cytokine storm syndrome and direct renal injury by the virus.
4. Diagnosis and laboratory features of COVID-19 infection:
· Low lymphocyte / white blood cell ratio had fatal outcomes.
· High CRP (60.7%) is linked to unfavourable outcome – ARDS, myocardial damage and death.
· Higher serum ferritin is associated with ARDS development and death.
· High IL-6 levels (52%) – novel biomarker, a/w increased risk of mortality in COVID-19
Imaging:
CXR – may show patchy consolidation; HRCT chest to be done when there is high clinical suspicion, with CXR normal / uncertain features in seriously ill patient.
5. Management of COVID-19 infection:
A. Mild infections: the usual practice is to reduce immunosuppression – withhold antiproliferative suggested.
B. Severe infection with requirement to mechanical ventilation: to maintain corticosteroids, hold antiproliferative and to argue about ceasing CNIs.
C. Remdesivir-treated patients had 31% faster time to recovery when compared to control.
D. CRRT may play a role in the management of AKI in COVID-19 patients. It was assumed that high-volume hemofiltration could remove inflammatory cytokines (tumour necrosis factor, IL-6, and IL-1β) involved in the pathogenesis of renal injury.
Level of evidence provided by this article:
case series – level of evidence grade 5.
The impact factor of a journal:
Journal impact factor (JIF) is sciento-metric index calculated by Clarivate, that reflects annual average number of citations of articles published in last 2years. indexed by Clarivate’s Web of Science.
Limitations of the JIF
· Some journals increase impact factor by reducing the number of scholarly records.
· Extension of the impact factor to the assessment of journal quality or individual authors is inappropriate.
· Extension of the impact factor to cross-discipline journal comparison is also inappropriate.
· Those who choose to use the impact factor as a comparative tool should be aware of the nature and premise of its derivation and also of its inherent flaws and practical limitations.
Dear All
You have noticed that I published this article before the publication of the results of the RECOVERY trial. Do you think I would have treated these patients differently?
Dear Prof. Ahmad:
You have noticed that I published this article before the publication of the results of the RECOVERY trial. Do you think I would have treated these patients differently?
“No”
for 7 of 8 patient – (mild to moderate illness) : general supportive care was only treatment required; 1 patient was managed even as outpatient.
However, 1 patient with severe illness (Cytokine storm Syndrome), required ICU admission, ventilatory support, CVVH. Only this patient would have been treated according to the Recovery Trial regimen (i.e IV dexamethasone 6 mg daily till recovery +/- Tocilizumab) should it be published that time.
RECOVERY trial used 4 therapeutic options – dexamethasone, tocilizumab, baricitinib and casirivimab-imdevimab can be used in critically ill COVID patients.
Only case 5 having high Serum IL-6, might have been benefitted from Tocilizumab + Dexamethasone, with good cover of antifungal and antimicrobial therapy.
The new coronavirus disease 2019 (COVID-19) infec- tion, emerged in Wuhan city, China, in December 2019, has close genomic structural similarities with the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused the SARS pandemic in 2003 and the middle east respiratory syndrome coronavirus (MERS-CoV) that caused (MERS) epidemic in 2012 [1, 2]. By April 26, 2020, infections related to COVID-19 affected people from 210 countries and caused 203,818 reported deaths worldwide.
In this report, we present our experience with 8 cases of COVID-19 infection in kidney transplant patients from Sheffield Kidney Institute, UK. The median age of patients was 48.5 years (ranging from 21 to 71 years), in- cluding 4 males and 4 females. Three patients had kidney transplantation within the last 3 months, and the rest were transplanted for more than a year.
In our case series, the most frequent presentation was fever (5 patients) and cough (5 patients). Fever was re- ported to be the most common symptom followed by cough . Two large studies demonstrated that 82–87% of their patients had a fever, while patients with cough ranged from 44 to 65.7%
All our patients had lymphopenia and a high CRP lev- el. Guan et al. reported that 83.2% of infected patients had lymphopenia on admission. Another study suggested a link between lymphopenia and acute respiratory dis- tress syndrome (ARDS) development . Two more re- ports demonstrated that patients who had a significantly low lymphocyte/white blood cell ratio both on admission and during hospitalization had fatal outcomes . Many studies showed that COVID-19 infection is associ- ated with high CRP. Guan et al. reported that 60.7% of patients had an elevated CRP, while severe cases had a higher level compared to the non-severe ones (81.5 vs. 56.4% for CRP).
Regarding the management, 6 of our patients had their antiproliferative drugs stopped, and they received sup- portive treatment; 1 patient needed oxygen therapy, and 1 required mechanical ventilation. On the other hand, none of our patients received specific antiviral drugs. When managing immunosuppression in kidney transplant re- cipients, the age, the severity of infection, the post-trans- plant duration, any other associated comorbidity, tissue mismatch, and any episodes of rejection should be consid- ered. Generally speaking, in mild infections, the usual practice is to continue or reduce the dose of immunosup- pressive drugs. While we declare that the small sample size of this study cannot give firm recommendations, we sug- gest discontinuation of the antiproliferative drugs (aza- thioprine and mycophenolate mofetil) while monitoring the patients closely.
We also found that short hospital stay with self-iso- lation on discharge reduces the burden on the health ser- vice and protect the staff and the public. Since remdisivir was approved for the treatment of COVID-19 and its in- teraction with CNI is yet unknown, we recommend treat- ment with remdisivir in a hospital setting where CNI drug level monitoring is available.
Please summarise this article:
Introduction: New coronavirus disease 2019 (COVID-19) infection, which is structurally similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV), affected people worldwide but the data regarding this infection among the transplant recipients is lacking. The article deals with 8 kidney transplant recipients infected with COVID-19.
Case reports:
Patient 1: 21-year-old female, 4 months post-transplant, presented with only fever without any respiratory involvement. Throat/ nasal swab for COVID-19 was positive. She was admitted and given supportive treatment, MMF stopped, and discharged after 2 days.
Patient 2: 71-year-old male, 4 years post-transplant, history of colon adenocarcinoma 6 months back and with chronic graft dysfunction, presented with dry cough and x ray chest showed bilateral lung involvement. Throat/ nasal swab for COVID-19 was positive. He was admitted and given supportive treatment, MMF stopped, and discharged after 2 days.
Patient 3: 50-year-old male, 2 months post-transplant, history of granulomatous polyangitis, presented with productive cough and a clear x ray chest. COVID-19 test was positive. MMF was stopped. He was advised home isolation and supportive treatment.
Patient 4: 63-year-old male, 15 years post-transplant, history of IgA nephropathy, presented with fever and elevated serum creatinine and x ray chest showed bilateral lung involvement. Test for COVID-19 was positive. Blood culture grew staphylococcus aureus, tacrolimus trough levels were low. He was admitted and given supportive treatment with intravenous antibiotics. MMF was stopped while tacrolimus dose was increased, and he was discharged after 7 days.
Patient 5: 47-year-old female, 5 months post-transplant, history of bronchial asthma presented with dry cough with shortness of breath and x ray chest showed bilateral lung involvement. Throat/ nasal swab for COVID-19 was positive. Serum creatinine, CRP, IL-2, and ferritin were elevated with urine culture growing E.coli. She was admitted in ICU and given supportive treatment, MMF stopped, and required non-invasive ventilation due to respiratory discomfort, but was intubated in view of worsening respiratory functions. Bronchoalveolar lavage revealed aspergillus. CVVH required in view of worsening renal function. Patient improved after 2 weeks, extubated and shifted to the medical ward from where she was discharged after 1 week.
Patient 6: 71-year-old female, 5 years post-transplant, history of diabetes mellitus, presented with fever and x ray chest showed bilateral lung involvement. Throat/ nasal swab for COVID-19 was positive. She was admitted and given supportive treatment, MMF stopped, and discharged after 4 days.
Patient 7: 40-year-old female, 3 years post-transplant, history of hypertension, presented with fever and dry cough. Throat/ nasal swab for COVID-19 was positive. She was admitted and given supportive treatment, MMF stopped, and discharged after 4 days.
Patient 8: 38-year-old male, 7 years post-transplant, history of chronic graft dysfunction, presented with productive cough and dyspnea for 2 days. Oxygen saturation was low on room air and x ray chest showed bilateral lung involvement. Throat/ nasal swab for COVID-19 was positive. He was admitted and given supportive treatment including oxygen support, tacrolimus dose reduced, azathioprine stopped, prednisolone dose increased, and discharged after 2 days.
Discussion: Transplant recipients have increased risk of infection due to underlying CKD, immunosuppression, and presence of co-morbidities like diabetes and hypertension (2-fold risk), and COPD (3-fold risk). The median age of the patients was 48.5 years, with 3 of the patients presenting within 3 months post-transplant.
Most common initial symptoms were fever and cough. 25% of the patients developed acute kidney injury (AKI), with one requiring renal replacement therapy. Renal involvement in COVID-19 is thought to be due to either cytokine storm syndrome, or due to direct viral renal injury. High volume hemofiltration could help by removing inflammatory cytokines.
All patients had lymphopenia and elevated CRP. Lymphopenia has been linked with development of acute respiratory distress syndrome (ARDS)while low lymphocyte/ white blood cell count ratio is associated with increased mortality. Elevated CRP and ferritin have been shown to be associated with ARDS, myocardial damage, and death. Elevated IL-6 has also been shown to be associated with increased mortality.
75% had chest x ray findings. So chest x ray should be the initial imaging of choice with CT reserved for seriously ill patients with uncertain x ray findings. One patient required ward-based oxygen therapy while another required intubation and mechanical ventilation. In mild infections, immunosuppressive drug dose, especially antiproliferative agents can be continued or reduced, while in severe cases calcineurin inhibitors would require cessation. The treatment should be individualized as per the clinical picture of the patient.
Convalescent plasma use as a treatment option is under investigation while remdesivir use has shown promising results with faster recovery in hospitalized patients.
Conclusion: COVID-19 presentation in kidney transplant recipients is similar to general population, with fever and cough being the commonest symptoms, and majority of the patients require supportive treatment alone for recovery. Short hospital stay and self-isolation on discharge with remdesivir use in hospitalized patients is advised.
2. What is the level of evidence provided by this article?
Level of evidence: Level 4: Case series
3. What is meant by the impact factor of a journal?
Impact factor of a journal implies the average number of citations received per article published in the journal over last 2 years.
Summary of the case series
Transplant clinicians commonly believe that kidney transplant recipients have a high infection risk due to long-term immunosuppression and associated comorbidities. In the absence of firm evidence, this brief series demonstrates experience in managing COVID-19 disease in renal transplant patients. 8 incidences of COVID-19 infection in recipients of kidney transplants The median age is 48.5; the range is 21–71. Sex of patients as follows 4 men and 4 women. Hypertension was the most prevalent associated comorbidity. The two most prevalent symptoms were fever and congestion. The primary radiological examination consisted of a portable chest X-ray. Also prevalent were lymphopenia, a high C-reactive protein level, and a very high ferritin level. One patient was treated as an outpatient, while the remaining seven required hospitalization, one of whom was admitted to the intensive therapy unit. Depending on oxygen saturation, intravenous fluid therapy, monitoring of renal function, and symptomatic treatment with or without ward-based oxygen therapy were administered. Discontinuation of the immunosuppressive antiproliferative medications in all patients Seven patients regained their health and were sent home to self-isolate. One individual required intensive care and mechanical ventilation. None received antiviral therapy or dexamethasone.
Discussion
Multiple risk factors, such as immunosuppression, underlying CKD, and comorbidities, place transplant patients at a high risk of infection. Patients with hypertension and diabetes have a risk of infection that is double that of COPD patients. The pathophysiology of renal involvement is still unknown, but hypotheses point to a cytokine storm syndrome or direct virus-induced renal injury. Continuous renal replacement therapy may be used to treat AKI in COVID-19 patients. Lymphopenia, elevated CRP levels, and elevated ferritin levels are associated with ARDS and poor outcomes. No unambiguous evidence supports the use of the IL-6 blocker tocilizumab in the treatment of COVID-19 in either transplant or nontransplant patients. Clinicians of all specialties must also be conversant with the radiological findings of COVID-19 on chest X-ray. Stop administering the antiproliferative medications (azathioprine and mycophenolate mofetil) while attentively monitoring the patients. In severe cases necessitating mechanical ventilation, discontinue calcineurin inhibitors while continuing corticosteroid treatment.
Conclusions
COVID-19-infected renal transplant recipients do not present differently than the general population. Supportive treatment may be sufficient or should be attempted initially. A brief hospital stay followed by self-isolation reduces the burden on the health service and protects the staff and the general public.
Case series of 8 KTRs
1.Patient 1
2.Patient 2
3.Patient 3
4.Patient 4
5.Patient 5
6.Patient 6
7.Patient 7
8.Patient 8
Conclusion
Majority of these patients presented with fever and had MMF discontinuation and best supportive care.
Level 4 evidence
Abstract:
Reports of 8 cases of kidney transplant recipients infected with COVID-19 of middle age including 4 males and 4 females. The most frequently associated comorbidity was hypertension and the common presenting features were fever and cough. The main radiological investigation was a portable chest X-ray. Other common features included lymphopenia, high C-reactive protein and a very high ferritin level.
Introduction:
The new coronavirus disease 2019 (COVID-19) infection, emerged in Wuhan city, China, in December 2019, has close genomic structural similarities with the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused the SARS pandemic in 2003 and the middle east respiratory syndrome coronavirus (MERS-CoV) that caused (MERS) epidemic in 2012 [1, 2]. By April 26, 2020, infections related to COVID-19 affected people from 210 countries and caused 203,818 reported deaths worldwide.
Case report:
Patient 1:
A 21-year-old female – who had a deceased donor kidney transplant in December 2019 presented on March 30 with fever (39.2°C).controlled hypertension with on other symptoms COVID-19 +VE treated by supportive care and discontinue MMF.
Patient 2:
A 71-year-old male with hypertensive nephropathy who received a kidney graft in February 2016. He had a history of colon adenocarcinoma in June 2019. His baseline Cr was 240–260 μmol/L. covid-19 test is +ve ,treated with supportive management and discontinue MMF.
Patient 3:
A 50-year-old male with a history of Wegner’s granulomatosis received a live donor kidney transplant in February 2020. He presented on April 3 with productive cough, and was tested positive for SARS-CoV-2 RNA despite unremarkable clinical examination. . The management included discontinuation of MMF, reduction of tacrolimus dose, and self-isolation at home. He was advised to drink plenty of fluids and report to the unit any new symptoms
Patient 4:
A 63-year-old male with a history of IgA nephropathy with a deceased donor kidney transplant in December 2005. He is hypertensive and maintained on calcium channel blockers. He presented on March 20 with fever (38.8°C) and acute kidney injury (AKI; Cr 297 μmol/L, baseline 110 μmol/L). The chest X-ray showed patchy bilateral consolidation, and SARS-CoV-2 RNA was positive. Blood culture was positive for staphylococcus aureus. Serum C-reactive protein (CRP) was 175 mg/L, and serum ferritin was 929 μg/L. treated with IV broad-spectrum antibiotics and paracetamol, stopped MMF and increased the tacrolimus dose. Kidney function tests improved. The patient recovered and discharged.
Patient 5:
A47-year-old female with bronchial asthma received a deceased donor kidney transplant in December 2019. c/o dry cough and shortness of breath but no fever. O/E: tachypnoea with a respiratory rate of 36 breaths/min, and the peripheral oxygen saturation was 80%. Investigations: lab shows AKI and mild proteinuria. Chest X-ray revealed bilateral middle and lower zone consolidation. Nose and throat viral swabs for COVID-19 were positive.
patient admitted to the intensive therapy unit (ITU) for non-invasive ventilation . Her respiratory functions got worse, and she required intubation and invasive ventilation.
Bronchoalveolar lavage showed moderate growth of aspergillus. She received broad-spectrum antibiotics and antifungals. No specific antiviral drugs were given.
MMF was discontinued. Her kidney functions deteriorated, and she became anuric; therefore, CVVH was commenced. After 14 days, she was weaned off mechanical ventilation and transferred from the ITU to the medical ward. Her kidney function improved and discharged home.
Patient 6:
A 71-year-old female with type II diabetes, received deceased donor kidney transplantation. C/O: fever (38.5°C) and no other complaint. Chest X-ray showed bilateral peripheral mid and lower zone consolidation. Nasal and throat swabs were positive for COVID-19 RNA.
RFT normal, and microbiological tests were negative. She was admitted to the medical ward for adequate hydration and symptomatic treatment. MMF was discontinued and discharged after 4 days with full recovery.
Patient 7:
A 40-year-old female with hypertension received deceased donor kidney transplantation. on 10th April.
C/O: fever (39°C) and dry cough . Nose and throat swabs for COVID-19 RNA were positive. Kidney function tests were stable and microbiological analyses were negative. Patient admitted for supportive management with IV fluid and paracetamol. MMF was discontinued, with good recovery and discharged home.
Patient 8:
A 38-year-old male with a failing kidney transplant from June 2013 presented with productive cough shortness of breath for 2 days. COVID-19 test positive and he was desaturated.
Management: discontinuation of azathioprine, reduction of tacrolimus dose, and increase of prednisolone dose to 15 mg OD. He did not require any dialysis. Oxygen saturation recovered to >95% on room air, and the patient was discharged after 2 days.
Discussion:
In this report three patients had kidney transplantation within the last 3 months, and the rest were transplanted for more than a year.
The most initial symptoms is fever and cough
Transplant patients are at a high risk of infection due to multiple risk factors, including immunosuppression, underlying CKD, and associated comorbidities.
In mild infection we continue or reduce the immunosuppressive therapy and stopped in severe infection.
Conclusion:
In this report COVID-19 presentation like general population in its symptoms .and managed by supportive care first.
we recommend treatment with remdesivir in a hospital setting where CNI drug level monitoring is available.
We recommend treatment with remdisivir in a hospital setting where CNI drug level monitoring is available.
Level of evidence is IV
COVID-19 infection structurally similar to SARS-CoV and MERS-CoV. Data regarding this infection among the transplant recipients is still lacking. The article summarized 8 kidney transplant recipients infected with COVID-19.
KTR have increased risk of infection due to underlying CKD, immunosuppression, and presence of co-morbidities like diabetes and hypertension (2-fold risk), and COPD (3-fold risk). The median age was 48.5 years. 3 patients presenting within 3 months post-transplant.
Most common initial symptoms were fever and cough. 25% of the patients developed acute kidney injury (AKI), with one requiring renal replacement therapy. Renal involvement in COVID-19 is thought to be due to either cytokine storm syndrome, or due to direct viral renal injury. High volume hemofiltration could help by removing inflammatory cytokines.
All patients had lymphopenia and elevated CRP. Lymphopenia has been associated with development of ARDS while low lymphocyte/ WBC count ratio is associated with increased mortality. Elevated CRP and ferritin have been shown to be associated with ARDS, myocardial damage, and death. Elevated IL-6 has also been shown to be associated with increased mortality.
75% had chest x ray findings. So chest x ray should be the initial imaging of choice with CT reserved for seriously ill patients with uncertain x ray findings.
In mild infections, immunosuppressive drug dose, especially antiproliferative agents can be continued or reduced, while in severe cases CNI would require cessation. The treatment should be individualized as per the clinical picture of the patient.
Convalescent plasma use as a treatment option is under investigation while remdesivir use has shown promising results with faster recovery in hospitalized patients.
COVID-19 presentation in KTR is similar to general population, with fever and cough being the commonest symptoms, and majority of the patients require supportive treatment alone for recovery.
Short hospital stay and self-isolation on discharge with remdesivir use in hospitalized patients is advised.
What is the level of evidence provided by this article?
Level 4: Case series
What is meant by the impact factor of a journal?
Impact factor of a journal implies the average number of citations received per article published in the journal over last 2 years.
Q1- Please summarise this article.
ntroduction :
The new coronavirus disease 2019 (COVID-19) infection, emerged in Wuhan city, China, in December 2019,
This article report 8 covid 19 infected kidney transplant patient.
Case Reports :
Patient 1:
a 21-year-old female – who had a deceased donor kidney transplant in December 2019 presented on March 30 with fever (39.2°C) ,no other symptoms ,positive covid ,managed by supportive and stop of ant proliferative i.e. MMF.
Patient 2:
a 71-year-old male with hypertensive nephropathy who received a kidney graft in February 2016. He had a history of colon adenocarcinoma in June 2019. His baseline Cr was 240–260 “mol/L. His immunosuppressive regimen included prednisolone 5 mg OD, tacrolimus (trough level was 6.4 ng/mL), and MMF 250 mg BD. He presented with a dry cough with no other symptoms. a chest X-ray revealed a patchy bilateral consolidation. He was tested positive for COVID-19. MMF discontinued and received supportive treatment IV fluid and symptomatic treatment. He was discharged 2 days later with stable kidney functions.
Patient 3:
a 50-year-old male with a history of Wegner’s granulomatosis received a live donor kidney transplant in February 2020. He presented with productive cough and was tested positive for SARS-CoV-2 RNA despite unremarkable clinical examination. The chest X-ray was clear, and kidney function tests were stable. His immunosuppressive drugs were prednisolone 5 mg OD, tacrolimus (trough level was 13.4 ng/mL), and MMF 500 mg BD. The management included discontinuation of MMF, reduction
of tacrolimus dose, and self-isolation at home. He was advised to drink plenty of fluids and report to the unit any new symptoms.
Patient 4:
a 63-year-old male with a history of IgA nephropathy with a deceased donor kidney transplant in December 2005. He presented with fever (38.8°C) and acute kidney injury (AKI; Cr 297 “mol/L, baseline 110 “mol/L). The chest X-ray showed patchy bilateral consolidation, and SARS-CoV-2 RNA was positive. Blood culture was positive for staphylococcus aureus. Serum (CRP) was 175 mg/L, and serum ferritin
was 929 “g/L. His immunosuppressive regimen was prednisolone 5 mg OD, tacrolimus (trough level was 2.7 ng/mL), and MMF 500 mg BD. The patient was admitted and received IV broad-spectrum antibiotics and paracetamol. We stopped MMF and increased the tacrolimus dose. Kidney function tests improved (serum Cr decreased to 113 “mol/L). The patient recovered and discharged home after 7 days.
Patient 5:
A 47-year-old female with bronchial asthma received a deceased donor kidney transplant in December 2019. She was maintained on prednisolone 5 mg OD, tacrolimus with levels between
5 and 7 ng/mL, and MMF 250 mg BD. She presented on April 6 with dry cough and shortness of breath but no fever. Chest X-ray revealed bilateral middle and lower zone consolidation. COVID-19 were positive. Kidney function tests showed AKI (Cr 302 “mol/L and baseline 162
“mol/L), and mild proteinuria (urine protein/Cr ratio 127 mg/
mmol and baseline <30 mg/mmol). Microbiology workup showed positive urine culture for E. coli . Serum CRP on admission was 344 mg/L and ferritin 2684 “g/L, with leukocytosis (white cell counts 25.8 × 109/L) and lymphopenia (lymphocyte count 0.7 × 109/L). Serum interleukin-6 was 22.2 pg/mL
(n = 0–7 pg/mL). She was tachypnoeic with a respiratory rate of 36 breaths/min, and the peripheral oxygen saturation was 80%, therefore admitted to the intensive therapy unit (ITU) for non-invasive
ventilation . she required intubation and invasive ventilation. Bronchoalveolar lavage showed moderate growth of aspergillus. She received broad-spectrum antibiotics and antifungals. MMF was discontinued. Her kidney functions deteriorated, and she became anuric; therefore, continuous veno-venous haemodiafiltration (CVVH) was commenced. After 14 days, she was weaned off mechanical ventilation and transferred from the ITU to the medical ward. Her kidney functions improved (estimated glomerular filtration rate was 17 mL/min per 1.73 m2, urine protein/ Cr ratio, 40 mg/
Patient 6:
A 71-year-old female with type II diabetes, received deceased donor kidney transplantation in November 2015. Her immunosuppressive therapy included prednisolone, tacrolimus, and MMF. She presented on April 2 with fever (38.5°C) and no other complaint. Chest X-ray showed bilateral peripheral mid and lower zone consolidation. positive for COVID-19 RNA. Kidney function tests showed no change from baseline, and microbiological tests were negative. Serum CRP was 19 mg/L, while serum ferritin was 1,835 “g/L. She was admitted to the medical ward for adequate hydration and symptomatic treatment. MMF was discontinued and discharged after 4 days with full recovery.
Patient 7:
A 40-year-old female with hypertension received deceased donor kidney transplantation in June 2017. She is maintained on prednisolone, tacrolimus, and MMF. On April 10, she presented with fever (39°C) and dry cough . COVID-19 RNA were positive. Kidney function tests were stable and microbiological analyses were negative. She was admitted to the medical ward, where MMF was discontinued, Paracetamol and IV fluids were administered and discharged after 4 days with full recovery.
Patient 8:
A 38-year-old male with a failing kidney transplant from June 2013 presented with productive cough (of clear sputum) and shortness of breath for 2 days. He was maintained on prednisolone 5 mg OD, tacrolimus, and azathioprine. On admission on March 20, he had tachypnoea and hypoxaemia with oxygen saturation of 89% on room air, which improved to >96% on 4 L/min oxygen through a nasal cannula. Positive for COVID-19 RNA. Kidney function tests remained unchanged (Cr 648 “mol/L) despite the high baseline Cr. Chest X-ray revealed bilateral infiltrates. Management included discontinuation of azathioprine, reduction of tacrolimus dose, and increase of prednisolone dose to 15 mg OD. He did not require any dialysis. Oxygen saturation recovered to >95% on room air, and the patient was discharged after 2 days.
Discussion
The most common initial symptoms were fever (5 patients) and cough
(5 patients). All 8 patients were receiving prednisone and
tacrolimus, 7 patients were receiving mycophenolate
mofetil, and 1 patient was receiving azathioprine. Two
patients had AKI (cases 4 & 5); 1 of them required continuous veno-venous hemofiltration (case 5). Blood results showed that all patients had lymphopenia and high CRP.
chest X-ray was performed in 7 patients, which was clear
in 2 of them,
One managed as an outpatient
and advised to self-isolate at home, with the remaining 7
requiring hospital admission.
One patient required ITU
admission, where she needed mechanical ventilation
(case 5). Bronchoalveolar lavage of this patient confirmed
aspergillosis for which she is receiving antifungal treatment
(another contributing factor for deterioration). Another
patient required ward-based oxygen therapy (case
8). The other 6 patients received supportive therapy on
the renal ward.
Antiproliferative immunosuppressive drugs were discontinued for all patients.
Transplant patients are at a high risk of infection due to multiple risk factors, including :
1- immunosuppression,
2- underlying CKD,
3- associated comorbidities, especially hypertension and diabetes .
Many studies reported that hypertensive and diabetic patients have a double-fold risk of infection, while COPD patients have a 5-fold risk.
One study report 1% of COVID-19 patients had a history of malignancy, which was higher than the prevalence of cancer in the overall Chinese population (0.29%).
In our case series, the most frequent presentation was
fever (5 patients) and cough (5 patients).
Two of our patients had AKI , recent studies showed a higher frequency of renal abnormalities.
Cheng et al. reported that among 710 patients, 44% had proteinuria, 26.7% had haematuria, and 14.1% had high serum Cr.
The pathophysiology of renal involvement is still
unclear,
1- cytokine storm syndrome.
2- direct renal injury by the virus.
In cases of AKI associated with SARS and MERS, continuous renal replacement therapy showed promising results . It was assumed that high-volume hemofiltration could remove inflammatory cytokines (tumour necrosis factor, IL-6, and IL-1) involved in the pathogenesis of renal injury .
Therefore, continuous renal replacement therapy may play a role in the management of AKI in COVID-19 patients.
Two more reports demonstrated that patients who had a significantly low lymphocyte/white blood cell ratio both on admission and during hospitalization had fatal outcomes
Management :
1- 6 of our patients had their antiproliferative drugs stopped, and they received supportive treatment; 1 patient needed oxygen therapy, and 1 required mechanical ventilation.
2- None of our patients received specific antiviral drugs.
3- When managing immunosuppression in kidney transplant recipients, the following should be considered :
a. the age,
b. the severity of infection,
c. the post-transplant duration,
d. associated comorbidity,
e. Tissue mismatch.
f. any episodes of rejection .
4- in mild infections, the usual practice is to continue or reduce the dose of immunosuppressive drugs.
5- The author suggest discontinuation of the antiproliferative drugs (azathioprine and mycophenolate mofetil) while monitoring the patients closely. Although the author prefer to stop the anti -proliferative drugs first in cases of severe infection.
6- In severe cases requiring mechanical ventilation, we can argue about ceasing calcineurin inhibitors while maintaining corticosteroid therapy.
7- convalescent plasma – derived from the blood of recovered patients – was used as a treatment option but its efficacy was questionable.
8- combination of lopinavir and ritonavir were discouraging.
9- remdesivir – the US Food and Drug Administration has authorized the use of remdesivir as a treatment option for hospitalized COVID-19 patients.
Q2- What is the level of evidence provided by this article?
Level of evidence 4 .
Q3- What is meant by the impact factor of a journal?
Impact factor is commonly used to evaluate the relative importance of a journal within its field and to measure the frequency with which the “average article” in a journal has been cited in a particular time period. Journal which publishes more review articles will get highest IFs
Abstract
This short series demonstrates experience in managing COVID-19 disease in renal transplant patients in the absence of strong evidence.
The most frequently associated comorbidity was hypertension.
The most common presenting features were fever and cough.
The main radiological investigation was a portable chest X-ray.
Other common features included lymphopenia, high C-reactive protein, and a very high ferritin level.
Management included supportive treatment (intravenous fluid therapy, monitoring renal function, and symptomatic treatment with or without ward-based oxygen therapy depending on oxygen saturation) and discontinuation of the antiproliferative immunosuppressive drugs.
Supportive treatment could be sufficient for the management or to be tried first.
Introduction
In the UK, mortality cases exceeded 30,000 so far. There is a common belief among transplant clinicians that kidney transplant recipients have a high risk of infection due to long-term immunosuppression and associated comorbidities. Data, clinical picture, and outcomes of COVID-19 in kidney transplant recipients are scarce.
Discussion
Many studies showed that COVID-19 infection is associated with high CRP. Guan et al. reported that 60.7% of patients had an elevated CRP, while severe cases had a higher level compared to the non-severe ones (81.5 vs. 56.4% for CRP).
Other reports noticed that high CRP could be linked to unfavourable outcomes, such as ARDS development ,myocardial damage ,and death .
Serum ferritin was measured in only 3 of our patients, and the level was very high. Many reports suggested that higher serum ferritin is associated with ARDS development and death .Ferritin is an acute-phase protein, but we are not sure about the sensitivity and specificity concerning the outcome.
IL-6 is considered a novel biomarker for COVID-19 diagnosis.
Other studies suggested that increased IL-6 levels can be associated with an increased risk of mortality.
there is no clear evidence to support the role of IL-6 blocker (tocilizumab) in treatment of COVID-19 in both transplant and non-transplant population.
The British Society of Thoracic Imaging (BSTI) issued guidelines which state that there is no recommended use of CT unless there is high suspicion with normal or uncertain appearance of CXR in a seriously ill patient .
It is also essential for clinicians of all specialities to be familiar with the radiological findings of COVID-19 on chest X-ray.
Generally speaking, in mild infections, the usual practice is to continue or reduce the dose of immunosuppressive drugs.
we suggest discontinuation of the antiproliferative drugs (azathioprine and mycophenolate mofetil) while monitoring the patients closely.
Remdesivir was used as a compassionate treatment that showed promising results .
Besides, the Adaptive COVID-19 Treatment Trial (NCT04280705) proved that remdesivir-treated patients had 31% faster time to recovery when compared to control .
Based on the previous results, the US Food and Drug Administration has authorized the use of remdesivir as a treatment option for hospitalized COVID-19 patients .
Conclusion
In the above report, the presentations of COVID-19 infected renal transplant patients were not different from the general population where fever and cough were the most frequent symptoms. We believe that our transplant patients did not behave differently from the general population as far as COVID-19 infection is concerned. Because of the small sample size, we could not evaluate the effect of immunosuppression on the course of the disease, but at least it is not a detrimental effect. Based on our experience, supportive treatment could be sufficient or at least to be tried first. It is worth mentioning that the clinical examination supported by simple bedside measures such as oxygen saturation and portable CXR rather than CT scan could be enough and limit the spread of infection. We also found that short hospital stay with self-isolation on discharge reduces the burden on the health service and protect the staff and the public. Since remdisivir was approved for the treatment of COVID-19 and its interaction with CNI is yet unknown, we recommend treatment with remdisivir in a hospital setting where CNI drug level monitoring is available.
level of evidence 4
Abstract:
Reports of 8 cases of kidney transplant recipients infected with COVID-19 (median age = 48.5 years; range = 21–71 years), including 4 males and 4 females. The most frequently associated comorbidity was hypertension.
The most common presenting features were fever and cough. The main radiological investigation was a portable chest X-ray. Other common features included lymphopenia, high C-reactive protei and a very high ferritin level.
Introduction :
The new coronavirus disease 2019 (COVID-19) infection, emerged in Wuhan city, China, in December 2019, Data, clinical picture, and outcomes of COVID-19 in kidney transplant recipients are scarce Therefore, we report 8 cases of kidney transplant recipients infected with COVID-19.
Case Reports :
Patient 1:
a 21-year-old female – who had a deceased donor kidney transplant in December 2019 presented on March 30 with fever (39.2°C) ,no other symptoms ,positive covid ,managed by supportive and stop of ant proliferative i.e. MMF.
patient 2:
a 71-year-old male with hypertensive nephropathy who received a kidney graft in February 2016. He had a history of colon adenocarcinoma in June 2019. His baseline Cr was 240–260 μmol/L. test positive for covid-19 ,treated with stop of MMF and supportive treatment.
patient 3:
a 50-year-old male with a history of Wegner’s granulomatosis received a live donor kidney transplant in February 2020. He presented on April 3 with productive cough and was tested positive for SARS-CoV-2 RNA despite unremarkable clinical examination.
the management included discontinuation of MMF, reduction of tacrolimus dose, and self-isolation at home.
Patient 4:
a 63-year-old male with a history of IgA nephropathy with a deceased donor kidney transplant in December 2005.
presented on March 20 with fever (38.8°C) and acute kidney injury (AKI; Cr 297 μmol/L, baseline 110 μmol/L). The chest X-ray showed patchy bilateral consolidation, and SARS-CoV-2 RNA was positive. Blood culture was positive for staphylococcus aureus.
stopped MMF and increased the tacrolimus dose. K
idney function tests improved (serum Cr decreased to 113 μmol/L). patient discharged stable.
Patient 5:
A 47-year-old female with bronchial asthma received a deceased donor kidney transplant in December 2019. She presented with dry cough and shortness of breath but no fever. Chest X-ray revealed bilateral middle and lower zone consolidation. Nose and throat viral swabs for COVID-19 were positive. Kidney function tests showed AKI (Cr 302 μmol/L and baseline 162 μmol/L), and mild proteinuria (urine protein/Cr ratio 127.
She was tachypnoeic with a respiratory rate of 36 breaths/min, and the peripheral oxygen saturation was 80%, therefore admitted to the intensive therapy unit (ITU) for non-invasive ventilation . Her respiratory functions got worse, and she required intubation and invasive ventilation.
Bronchoalveolar lavage showed moderate growth of aspergillus. She received broad-spectrum antibiotics and antifungals. No specific antiviral drugs were given.
MMF was discontinued. Her kidney functions deteriorated, and she became anuric; therefore, CVVH was commenced. After 14 days, she was weaned off mechanical ventilation and transferred from the ITU to the medical ward. Her kidney function improved and discharged home.
Patient 6:
A 71-year-old female with type II diabetes, received deceased donor kidney transplantation . . She presented with fever (38.5°C) and no other complaint. Chest X-ray showed bilateral peripheral mid and lower zone consolidation. Nasal and throat swabs were positive for COVID-19 RNA.
Kidney function tests showed no change from baseline, and microbiological tests were negative. She was admitted to the medical ward for adequate hydration and symptomatic treatment. MMF was discontinued and discharged after 4 days with full recovery.
Patient 7:
A 40-year-old female with hypertension received deceased donor kidney transplantation . On April 10, she presented with fever (39°C) and dry cough with no other symptoms. Nose and throat swabs for COVID-19 RNA were positive. Kidney function tests were stable and microbiological analyses were negative. She was admitted to the medical ward, where MMF was discontinued, Paracetamol and IV fluids. good recovery and discharged home.
Patient 8
: A 38-year-old male with a failing kidney transplant from June 2013 presented with productive cough shortness of breath for 2 days.test positive and she was desaturated.
Management included discontinuation of azathioprine, reduction of tacrolimus dose, and increase of prednisolone dose to 15 mg OD. He did not require any dialysis. Oxygen saturation recovered to >95% on room air, and the patient was discharged after 2 days.
Discussion:
Fever was reported to be the most common symptom followed by cough.
renal abnormalities. Cheng et al. reported that among 710 patients, 44% had proteinuria, 26.7% had haematuria, and 14.1% had high serum Cr.
Therefore, continuous renal replacement therapy may play a role in the management of AKI in COVID-19 patient.
Al Many reports suggested that higher serum ferritin is associated with ARDS development [and death .
generally speaking, in mild infections, the usual practice is to continue or reduce the dose of immunosuppressive drugs and stop in severe infection.
Conclusion:
In the above report, the presentations of COVID-19 infected renal transplant patients were not different from the general population where fever and cough were the most frequent symptoms.
supportive treatment could be sufficient or at least to be tried first.
It is worth mentioning that the clinical examination supported by simple bedside measures such as oxygen saturation and portable CXR rather than CT scan .
Since remdisivir was approved for the treatment of COVID-19 and its interaction with CNI is yet unknown, we recommend treatment with remdisivir in a hospital setting where CNI drug level monitoring is available.
level of evidence IV.
article summaries 8 cases of post transplant covid disease
cough and fever is common presentation
supportive therapy is required
Hypertension is commonest comorbidity
renal involvement is seen in 2 cases , but it is reported to be low in covid cases
stopping antiproliferative drugs is advised
CXR is common test to monitor lung image
general behaviour is same like non transplant patients
level 1 evidence
impact factor
It reflect how commonly the articles are cited after its publication in that jounal
number of citation divided by total number of publication of previous 2 years
high the impact factor , better is the reputation or acceptance of that journal
You have noticed that I published this article before the publication of the results of the RECOVERY trial. Do you think I would have treated these patients differently?You have noticed that I published this article before the publication of the results of the RECOVERY trial. Do you think I would have treated these patients differently?
short answer is NO
most cases are early in the phase and can be managed on supportive care
1. Please summarise this article.
Introduction: New coronavirus disease 2019 (COVID-19) infection, which is structurally similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV), affected people worldwide but the data regarding this infection among the transplant recipients is lacking. The article deals with 8 kidney transplant recipients infected with COVID-19.
Case reports:
Patient 1: 21-year-old female, 4 months post-transplant, presented with only fever without any respiratory involvement. Throat/ nasal swab for COVID-19 was positive. She was admitted and given supportive treatment, MMF stopped, and discharged after 2 days.
Patient 2: 71-year-old male, 4 years post-transplant, history of colon adenocarcinoma 6 months back and with chronic graft dysfunction, presented with dry cough and x ray chest showed bilateral lung involvement. Throat/ nasal swab for COVID-19 was positive. He was admitted and given supportive treatment, MMF stopped, and discharged after 2 days.
Patient 3: 50-year-old male, 2 months post-transplant, history of granulomatous polyangitis, presented with productive cough and a clear x ray chest. COVID-19 test was positive. MMF was stopped. He was advised home isolation and supportive treatment.
Patient 4: 63-year-old male, 15 years post-transplant, history of IgA nephropathy, presented with fever and elevated serum creatinine and x ray chest showed bilateral lung involvement. Test for COVID-19 was positive. Blood culture grew staphylococcus aureus, tacrolimus trough levels were low. He was admitted and given supportive treatment with intravenous antibiotics. MMF was stopped while tacrolimus dose was increased, and he was discharged after 7 days.
Patient 5: 47-year-old female, 5 months post-transplant, history of bronchial asthma presented with dry cough with shortness of breath and x ray chest showed bilateral lung involvement. Throat/ nasal swab for COVID-19 was positive. Serum creatinine, CRP, IL-2, and ferritin were elevated with urine culture growing E.coli. She was admitted in ICU and given supportive treatment, MMF stopped, and required non-invasive ventilation due to respiratory discomfort, but was intubated in view of worsening respiratory functions. Bronchoalveolar lavage revealed aspergillus. CVVH required in view of worsening renal function. Patient improved after 2 weeks, extubated and shifted to the medical ward from where she was discharged after 1 week.
Patient 6: 71-year-old female, 5 years post-transplant, history of diabetes mellitus, presented with fever and x ray chest showed bilateral lung involvement. Throat/ nasal swab for COVID-19 was positive. She was admitted and given supportive treatment, MMF stopped, and discharged after 4 days.
Patient 7: 40-year-old female, 3 years post-transplant, history of hypertension, presented with fever and dry cough. Throat/ nasal swab for COVID-19 was positive. She was admitted and given supportive treatment, MMF stopped, and discharged after 4 days.
Patient 8: 38-year-old male, 7 years post-transplant, history of chronic graft dysfunction, presented with productive cough and dyspnea for 2 days. Oxygen saturation was low on room air and x ray chest showed bilateral lung involvement. Throat/ nasal swab for COVID-19 was positive. He was admitted and given supportive treatment including oxygen support, tacrolimus dose reduced, azathioprine stopped, prednisolone dose increased, and discharged after 2 days.
Discussion: Transplant recipients have increased risk of infection due to underlying CKD, immunosuppression, and presence of co-morbidities like diabetes and hypertension (2-fold risk), and COPD (3-fold risk). The median age of the patients was 48.5 years, with 3 of the patients presenting within 3 months post-transplant.
Most common initial symptoms were fever and cough. 25% of the patients developed acute kidney injury (AKI), with one requiring renal replacement therapy. Renal involvement in COVID-19 is thought to be due to either cytokine storm syndrome, or due to direct viral renal injury. High volume hemofiltration could help by removing inflammatory cytokines.
All patients had lymphopenia and elevated CRP. Lymphopenia has been linked with development of acute respiratory distress syndrome (ARDS)while low lymphocyte/ white blood cell count ratio is associated with increased mortality. Elevated CRP and ferritin have been shown to be associated with ARDS, myocardial damage, and death. Elevated IL-6 has also been shown to be associated with increased mortality.
75% had chest x ray findings. So chest x ray should be the initial imaging of choice with CT reserved for seriously ill patients with uncertain x ray findings. One patient required ward-based oxygen therapy while another required intubation and mechanical ventilation. In mild infections, immunosuppressive drug dose, especially antiproliferative agents can be continued or reduced, while in severe cases calcineurin inhibitors would require cessation. The treatment should be individualized as per the clinical picture of the patient.
Convalescent plasma use as a treatment option is under investigation while remdesivir use has shown promising results with faster recovery in hospitalized patients.
Conclusion: COVID-19 presentation in kidney transplant recipients is similar to general population, with fever and cough being the commonest symptoms, and majority of the patients require supportive treatment alone for recovery. Short hospital stay and self-isolation on discharge with remdesivir use in hospitalized patients is advised.
2. What is the level of evidence provided by this article?
Level of evidence: Level 4: Case series
3. What is meant by the impact factor of a journal?
Impact factor of a journal implies the average number of citations received per article published in the journal over last 2 years.
Introduction
☆ COVID-19 has structure similar to (SARS-CoV) and (MERS-CoV)
☆ kidney transplant recipients have a high risk of infection
● A report 8 cases of kidney transplant recipients infected with COVID-19
Case Reports
● Patient 1:
☆ A 21-year-old female
☆ Recieved deceased RTx
☆ presented after 3 m with fever, unwell, with no respiratory symptoms.
☆ Clinical examination was unremarkable
☆ Chest X-ray was clear.
☆ Urine and blood cultures were negative. ☆ A nasal and throat swab for COVID-19 was positive.
☆ She is hypertensive
☆ She discharged after 2 days with full recovery and stable kidney functions.
● Patient 2:
☆ a 71-year-old male
☆ Received a kidney graft
☆ His IS regimen is pred, tac, MMF
☆ He was on CCBs and PPi .
☆ He presented with only a dry cough with stable vital signs.
☆ a chest X-ray revealed a patchy bilateral consolidation.
☆ A nasal and throat swab for COVID-19 was positive.
☆ He received supportive treatment IV fluid and symptomatic treatment.
☆ He was discharged 2 days later with stable kidney functions.
● Patient 3:
☆ a 50-year-old male
☆ A history of Wegner’s granulomatosis
☆ He received a live donor kidney
☆ He presented with productive cough
☆ He was positive for SARS-CoV-2 RNA
☆ clinical examination was negative
☆ The chest X-ray was clear
☆ kidney function tests were stable.
☆ His IS drugs were pred, tac, MMF
☆ MMF was discontinuated, tacrolimus had reduced, and self-isolation at home.
● Patient 4:
☆ a 63-year-old male
☆ Recieved a deceased RTx
☆ He presented with fever and AKI
☆ Chest X-ray showed patchy bilateral consolidation
☆ SARS-CoV-2 RNA was positive.
☆ His IS regimen was pred, tac, MMF
☆ MMF stopped and tac increased
☆ Kidney function tests improved
● Patient 5:
☆ A 47-year-old female
☆ Received a deceased RTx
☆ Her IS regimen was pred, tac, MMF
☆ She presented with dry cough and shortness of breath but no fever.
☆ Chest X-ray revealed bilateral middle and lower zone consolidation.
☆ Nose and throat viral swabs for COVID-19 were positive.
☆ AKI, mild proteinuria and positive urine culture for E. coli and negative blood culture.
☆ He admitted to ICU due to decreased
O2 sat %
☆ She received broad-spectrum antibiotics and antifungals.
☆ No specific antiviral drugs were given.
☆ MMF was discontinued.
☆ Her kidney functions deteriorated, and she began CVVH
☆ After 14 days, she was weaned off mechanical ventilation
☆ Her kidney functions improved
● Patient 6:
☆ A 71-year-old female
☆ Received deceased RTx
☆ Her IS therapy was pred, tac, MMF.
☆ She presented with only fever
☆ Chest X-ray showed bilateral peripheral mid and lower zone consolidation.
☆ Nasal and throat swabs were positive for COVID-19 RNA.
☆ Kidney function tests were stable
☆ MMF was discontinued
● Patient 7:
☆ A 40-year-old female
☆ She received deceased RTx
☆ Her IS therapy was pred, tac, MMF.
☆ She presented with fever and dry cough
☆ Nose and throat swabs for COVID-19 RNA were positive.
☆ Kidney function tests were stable
☆ MMF was discontinued
☆ He discharged after 4 d with full recover.
● Patient 8:
☆ A 38-year-old male
☆ with a failing kidney transplant
☆ presented with productive cough and shortness of breath
☆ He was on pred, tac, and AZA
☆ He had tachypnoea and hypoxaemia
☆ Nasal and throat swabs were positive for COVID-19 RNA.
Kidney function tests were stable
☆ Chest X-ray revealed bilateral infiltrates.
☆ Management included discontinuation of aza, reduction of tac, and increase of
pred, He did not require any dialysis.
☆ Oxygen saturation recovered
Discussion
● Median age = 48.5, range = 21–71 years
● 4 males and 4 females.
● 3 patients had RTx within the last 3 m and the rest were for more than a year
● The most features were fever and cough
● IS therapy was pred,tac, 7 (MMF),1(AZA)
● 2 had AKI and 1 required CVVH
● all pts had lymphopenia and high CRP.
● 3 pts had elevated serum ferritin
● The most comorbidity was hypertension
● Chest X-ray was clear in 2 pts, and viral pneumonia in the rest
● 1 patient was managed as an outpatient
● 7 required hospital admission
● 1 referred to the intensive therapy unit.
● Transplant patients are at a high risk of infection due to multiple risk factors, including immunosuppression, underlying CKD, and associated comorbidities, especially hypertension and diabetes
● Management included supportive treatment (intravenous fluid therapy, monitoring renal function, and symptomatic treatment with or without
ward-based oxygen therapy depending on oxygen saturation) and discontinuation of the antiproliferative immunosuppressive
● Theories suggest a cytokine storm syndrome or direct renal injury by the virus are the pathophysiology of renal involvement
● CRRT can remove inflammatory cytokines involved in the pathogenesis of renal injury and may play a role in the management of AKI in COVID-19 patients.
● High CRP and ferritin could be linked to unfavourable outcomes, such as ARDS , myocardial damage and death
● Seven patients recovered and One patient required intensive care treatment and mechanical ventilation.
● None of our patients received specific antiviral drugs.
● limitations :
☆ small sample size
☆ lacked control groups
● Treatment should be individualized based on the careful assessment of each patient.
● Currently, the US FDA investigates the efficacy of convalescent plasma as a treatment option for patients with severe COVID-19 infection
● Reports suggested that remdesivir can be effective against MERS-CoV and SARS-CoV infections
Conclusion
☆ Renal transplant patients were not different from the general population regarding to symptoms and behavior
☆ Supportive treatment could be sufficient or at least to be tried first.
☆ Short hospital stay with self-isolation
on discharge reduces the burden on the health service and protect the staff and the public.
● Level : 4
● The impact factor of the journal :
☆ Used to evaluate the relative importance of a journal within its field
☆ Measure the frequency with which the “average article” in a journal has been cited in a particular time period.
☆ Journal which publishes more review articles will get highest IFs
☆ In general, the impact factor of 10 or higher is considered remarkable, while 3 is good, and the average score is less than 1.
☆ It is calculated by dividing the number of citations in the JCR year by the total number of articles published in the two previous years
● As For recovery trail solid organ transplant recipients were not included
● RECOVERY trail reported that Baricitinib Dexamethasone, and Tocilizumab reduce deaths so dexamethazon can be used in these patients , as for Tocilizumab and Baricitinib data is sparse
● Recovery trail reported that Tocilizumab reduces deaths and shortens the time taken for patients to be successfully discharged from hospital, and reduces the need for a mechanical ventilator in patients hospitalised with COVID-19
but in SOT patients
A dministration of tocilizumab for treatment of severe COVID-19 among SOT recipients appeared to be safe but was not associated with reduced mortality and the requirement for mechanical ventilation but it was associated with a shorter hospital stay.
● RECOVERY trial reported that baricitinib reduces the risk of death when given to hospitalised patients with severe COVID-19.
● But in SOTR , NIH still recommends use of baricitinib for patients with severe or critical COVID-19 disease with rapid progression and advises that SOTR who receive baricitinib should be monitored closely for secondary infections
● So I think that is nothing could added to patients in this series cases especially the most of them weren’t severe cases
▪︎Amani H Yamani et al. Immun Inflamm Dis. 2022 Mar .Early use of tocilizumab in solid organ transplant recipients with COVID-19: A retrospective cohort study in Saudi Arabia
▪︎Am J Transplant ،2020 Nov; 20(11): 3198–3205. Tocilizumab for severe COVID-19 in solid organ transplant recipients: a matched cohort study
▪︎Bodro M, Cofan F, Ríos J, Herrera S, Linares L, Marcos MÁ, Moreno A, Diekmann F. Use of anti-cytokine therapy in kidney transplant recipients with COVID-19. J Clin Med. 2021;10(1551). [PMC free article] [PubMed]
Summary
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
This short series demonstrates experience in managing COVID-19 disease in renal transplant patients in the absence of strong evidence. 8 cases of kidney transplant recipients infected with COVID-19 were reported. There is a common belief among transplant clinicians that kidney transplant recipients have a high risk of infection due to long-term immunosuppression and associated comorbidities.
Clinical cases
Patient 1
21-year Femal with deceased donor transplantation
Symptoms- fever, no respiratory symptoms
Normal chest X-ray.
Immunosuppression- Tacrolimus 4mg + MMF 500mg/day + Prednisone 5mg.
Management-MMF was discontinued and discharged with stable renal function.
Patient 2
71 years Male with h/o colon adenocarcinoma
Symptom- dry cough
B/l pulmonary consolidations on chest X-ray.
Immunosuppression-Tacrolimus (trough 6.7ng/ml) + MMF 500mg/day + Prednisone 5mg
Management- Discontinued MMF and was discharged two days later with stable renal function.
Patient 3
50-year male with Wagener granulomatosis had living donor transplantation
Symptoms -Productive cough.
Normal X- rays and stable renal function
Immunosuppression- Tacrolimus (trough 13.4 ng/ml) + MMF 1g/day + prednisone 5mg.
Management- Discontinuation of MMF, reduction of tacrolimus dose and self-isolation at home.
Patient 4
63-year Male with IgA had deceased donor transplantation
Symptoms -Fever and acute kidney injury
Patchy bilateral pulmonary consolidation
Labs- high CRP, Blood c/s positive for staphylococcus aureus.
Immunosuppression- Tacrolimus (trough 2.7) + MMF 1g + Prednisone 5mg.
Management- increased the dose of tacrolimus and MMF was stopped with improvement in renal function, and he was discharged after seven days.
Patient 5
47 year female with bronchial asthma had deceased donor transplantation.
Symptoms- Dry cough and SOB but without fever
X-rays showed consolidations.
Labs- Urine c/s positive with e coli acute kidney injury. Elevated CRP and IL6. BAL showed aspergillosis.
Immunosuppression- Tacrolimus (trough 5-7 + MMF 500mg/day + Prednisone 5mg. Management -She needed ICU admission, intubation, CVVH. MMF was suspended. She received antifungal treatment for aspergillosis. She extubated her kidney function partially improved to Gfr17ml/min not requiring CVVH and discharged in 21 days.
Patient 6
71 years female with T2 DM had deceased donor transplantation.
Symptoms- fever.
X-rays consolidation.
Labs-There was no change in renal function.
Immunosuppression- tacrolimus + MMF + prednisone
Management- MMF was suspended, hospital admission, discharge after four days.
Patient 7
40-year female with HTN deceased donor.
Symptoms fever and dry cough.
Immunosuppression- Tacrolimus + MMF + Prednisone.
Management- MMF discontinued and discharged after four days.
Patient 8
38 year male with failing transplant kidney.
Symptoms- Productive cough and fever.
X ray showed infiltrates.
Immunosuppression-Tacrolimus + Azathioprine and prednisone.
Management- Discontinued Azathioprine, reduce Tacrolimus dose, Increased prednisolone, Needed oxygenation, not needed HD, discharged in 2 days
Antiproliferative immunosuppressive drugs were discontinued for all patients.
In this case series, the most frequent presentation was fever (5) and cough (5)
All patients had lymphopenia and a high CRP level.
5/8 had bilateral patchy consolidation.
Conclusion
Despite the small number of cases, discontinuing antiproliferative drugs is highly recommended. Maintaining corticosteroid therapy is recommended and treatment with remdesivir in a hospital setting where CNI drug level monitoring is available is recommended.
What is the level of evidence provided by this article?
Level 4 case series
What is meant by the impact factor of a journal?
Impact factor is commonly used to evaluate the relative importance of a journal within its field.
Impact Factor measures the frequency with which the “average article” in a journal has been cited in a particular time period.
The impact factor of a journal is calculated by dividing the number of current year citations to the source items published in that journal during the previous two years.
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
Introduction
· By April 26, 2020, infections related to COVID-19 were responsible for 203,818 reported deaths worldwide.
· Transplant clinicians believe that kidney transplant recipients have a high risk of infection because they are immunocompromised.
Case Reports
Patient 1: a 21-year-old female – who had a deceased donor kidney transplant in December 2019. She is hypertensive on calcium channel and β-blockers. She was on prednisone, tacrolimus, and MMF. Admitted with COVID-19, given IV fluids and paracetamol, MMF was stopped and discharged after 2 days with full recovery and stable kidney functions.
Patient 2: a 71-year-old male with hypertensive nephropathy who received a kidney graft in February 2016. He had a history of colon adenocarcinoma in June 2019. He is on prednisolone, tacrolimus, MMF, calcium channel blockers, and PPI. Admitted with COVID-19, MMF was stopped, given supportive treatment, and discharged 2 days later with stable kidney functions.
Patient 3: a 50-year-old male with a history of Wegner’s granulomatosis received a live donor kidney transplant in February 2020, presented with a productive cough, and had positive for SARS-CoV-2 RNA, MMF was stopped, tacrolimus dose reduced, and self-isolation at home.
Patient 4: a 63-year-old male with a history of IgA nephropathy with a deceased donor kidney transplant in December 2005. He is on CCB, prednisone, tacrolimus, and MMF. Presented with fever, AKI, bilateral patchy consolidation, +SARS-CoV-2 RNA, +Blood culture for staphylococcus aureus, high CRP, and ferritin. Admitted for broad-spectrum antibiotics, reduced tacrolimus dose, and MMF was stopped. Kidney function tests improved and the patient recovered and was discharged home after 7 days.
Patient 5: A 47-year-old female with bronchial asthma received a deceased donor kidney transplant in December 2019. On prednisolone, tacrolimus, and MMF. Presented with dry cough and shortness of breath without fever, bilateral consolidation, + COVID-19. Kidney function tests showed AKI, and mild proteinuria, positive urine culture for E. coli and negative blood culture. Very high CRP and ferritin. e admitted to the intensive therapy unit (ITU) for non-invasive ventilation but she deteriorated and required intubation and invasive ventilation. BAL showed aspergillus. MMF stopped, antibiotics and antifungals were given.
Patient 6: A 71-year-old female with type II diabetes, received deceased donor kidney transplantation in November 2015. She is on prednisolone, tacrolimus, and MMF. She presented with fever, bilateral peripheral mid and lower zone consolidation, and was positive for COVID-19 RNA. She was admitted for fluid therapy, MMF was stopped, and discharged after 4 days.
Patient 7: A 40-year-old female with hypertension received deceased donor kidney transplantation in June 2017. She is on prednisolone, tacrolimus, MMF, amlodipine and PPI. She was admitted with fever and + COVID-19 RNA. MMF was held, Paracetamol and IV fluids were given and discharged after 4 days with full recover.
Patient 8: A 38-year-old male with a failing kidney transplant from June 2013 presented with productive cough and shortness of breath for 2 days. He was on prednisolone, tacrolimus, and azathioprine. Admitted with tachypnoea and hypoxemia ( SaO2 89% on RA), which improved to >96% on 4 L/min oxygen through a nasal cannula. + COVID-19 RNA, high creatinine, and bilateral lung infiltrates. Azathioprine was stopped, tacrolimus dose reduced, and prednisolone dose was increased to 15 mg OD.
Discussion
· Hypertensive and diabetic patients have a double-fold risk of infection, while COPD patients have a 5-fold risk
· Liang et al. found that 1% of COVID-19 patients had a history of malignancy
· Many studies showed that COVID-19 infection is associated with high CRP, which linked to unfavorable outcomes.
· Some studies suggested that increased IL-6 levels can be associated with an increased risk of mortality.
· There is no clear evidence to support the role of IL-6 blocker (tocilizumab) in the treatment of COVID-19 in both transplant and non-transplant populations.
· portable chest X-ray is recommended to reduce the transmission of infection.
· Discontinuation of antiproliferative drugs in cases of severe infection is recommended.
· In severe cases requiring mechanical ventilation, calcineurin inhibitors should be stopped while maintaining corticosteroid therapy.
· Trial of the combination of lopinavir and ritonavir among SARS-CoV patients was discouraging.
· Drug Administration has authorized the use of remdesivir as a treatment option for hospitalized COVID-19 patients.
Conclusion
· There is no big difference between COVID-19 infected renal transplant patients and general population.
· supportive treatment should be tried first, and to give remdisivir in a hospital setting
The article of Prof Halawa and collaegues have shown outcome of 8 kidney transplant patients who suffered from Covid 19 during the pandemic.
All patients were discharged safely as one patient was managed as outpatient.
One patient needed Mechanical ventilation and dialysis support and luckily recovered and discharged later.
MMF was with held for all patients which is now considered as a standard of care for these patients.
Level of Evidence
Case series—articles written about a series of patients with a specific diagnosis—are also regarded as level 4 evidence.
Impact Factor?
The impact factor (IF) is a measure of the frequency with which the average article in a journal has been cited in a particular year. It is used to measure the importance or rank of a journal by calculating the times its articles are cited.
How Impact Factor is Calculated?
The calculation is based on a two-year period and involves dividing the number of times articles were cited by the number of articles that are citable.
Please summarise this article.
Introduction
· COVID-19 has close genomic structural similarities to SARS-CoV and MERS-CoV and has caused 203,818 reported deaths worldwide.
· 8 cases of kidney transplant recipients infected with COVID-19 were reported due to long-term immunosuppression and comorbidities.
Discussion
· 8 cases of COVID-19 infection in kidney transplant patients from Sheffield Kidney Institute, UK, with a median age of 48.5 years, median initial symptoms of fever, cough, prednisone, tacrolimus, mycophenolate mofetil, AKI, lymphopenia, high CRP, elevated serum ferritin, elevated IL-6, and a portable chest X-ray.
· 8 patients were managed as outpatients and advised to self-isolate at home, with 7 requiring hospital admission and 6 receiving supportive therapy on the renal ward. Antiproliferative immunosuppressive drugs were discontinued.
· Transplant patients are at a high risk of infection due to multiple risk factors, including immunosuppression, underlying CKD, and comorbidities, such as hypertension and diabetes.
· Liang et al. reported that 1% of COVID-19 patients had a history of malignancy, higher than the overall Chinese population.
· Fever was the most common symptom, followed by cough, with 82-87% of patients having fever and 44-65% with cough.
· The incidence of AKI in COVID-19 patients is low, but recent studies have shown a higher frequency of renal abnormalities, suggesting a cytokine storm syndrome or direct renal injury by the virus. Continuous renal replacement therapy may play a role in the management of AKI.
· Studies have shown that COVID-19 infection is associated with high CRP levels, which can be linked to unfavorable outcomes such as ARDS development, myocardial damage, and death.
· Serum ferritin was also found to be high, suggesting that higher serum ferritin is associated with ARDS development and death.
· The most important details are that in- creased IL-6 levels can be associated with an increased risk of mortality and that there is no clear evidence to support the role of IL-6 blocker (tocilizumab) in the treatment of COVID-19 in both transplant and non-transplant populations.
· CT decontamination may disrupt radiology service, and portable chest X-rays should be considered to reduce transmission of infection.
· Clinicians of all specialties should be familiar with the radiological findings of COVID-19 on chest X-rays.
· The most important details are that 6 of the patients had their antiproliferative drugs stopped, 1 needed oxygen therapy, 1 required mechanical ventilation, and none of the patients received specific antiviral drugs. The treatment should be individualized based on the individual assessment of each patient.
· The US Food and Drug Administration has authorized the use of remdesivir as a treatment option for patients with severe COVID-19 infection..
Conclusion
· The presentations of COVID-19-infected renal transplant patients were similar to the general population, with fever and cough being the most frequent symptoms.
· Supportive treatment, such as bedside measures such as oxygen saturation and portable CXR, and short hospital stay with self-isolation on discharge are recommended to reduce the burden on the health system and protect the public.
What is the level of evidence provided by this article?Case series Level IV
What is meant by the impact factor of a journal?It’s a measure of the relative importance of a journal within its field like the “average article” in a journal has been mentioned on average x number of times during y time period, The journals with the highest IFs are those that publish the most reviews.
Summarize the article:
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
8 cases of kidney transplant recipients(a group who is considered high risk ), presented with different symptoms and were treated with supportive measures in addition to stopping antimetabolites and were recovered and discharged in 2days with stable renal function.
They presented with one of these symptoms
· lethargy and unwell with fever
· dry cough, chest X-ray revealed a patchy bilateral consolidation
· productive cough, advised home isolation
· fever (38.8°C) and AKI, chest X-ray showed patchy bilateral consolidation. Positive blood culture with staph and high CRP and ferritin
· dry cough and shortness of breath, X-ray revealed bilateral middle and lower zone consolidation & AKI with mild proteinuria and urine culture positive for E. coli and negative blood culture. high CRP and ferritin with leukocytosis and lymphopenia. High serum interleukin. tachypnoea with a high respiratory rate and low oxygen saturation (80%), required admission to the intensive therapy unit (ITU) and intubated. BAL shows aspergillus. She required antibiotics anti fungal and dialysis , eventually improved and discharged in 7 days.
· Fever , Chest X-ray showed bilateral peripheral mid and lower zone consolidation. Stable Kidney function tests, high serum ferritin received symptomatic treatment and hydration and discharged in 4 days.
· fever (39°C) and dry cough Kidney function tests were stable improved in 4 days with symptomatic treatment.
· productive cough and breathing difficulty With tachypnoea and hypoxaemia with oxygen saturation of 89% on room air, Kidney function tests were stable .Chest X-ray showed bilateral infiltrates. patient recovered and discharged after 2 days.
It is noticed that the most frequent presentation was fever and cough , while All the patients had lymphopenia and a high CRP. IL-6 is considered a novel biomarker for COVID-19 diagnosis but found to be high in only 1 patient.
A chest X-ray had positive finding with bilateral patchy consolidation in almost all the cases, the auther suggested that portable chest X-ray should be considered to reduce the transmission of infection rather that CT scan. The Italian and British hospitals employ chest X-ray as a first-line triage tool as the results of COVID-19 testing.
Most of the patient were treated symptomatically , their antimetabolites drugs stopped, and they received supportive treatment. They improved , 2 of them had AKI however recovered.
none of our patients received specific antiviral drugs.
Other treatments were investigated such as efficacy of convalescent plasma and use of antivirals
reports suggested that remdesivir (a broad-spectrum antiviral nucleotide prodrug) can be effective against MERS-CoV and SARSCoV infections.
Level of evidence :
IV(anecdotal evidence including author independent opinion and review)
impact factor:The journal Impact Factor is an index that measures how frequently articles in a journal are cited in other research. This is calculated by dividing the number of citations received by articles published in that journal over the previous two years by the total number of articles published in that journal over the previous two years.
Summary:
Introduction:
Covid-19 infection, emerged in Wuhan, China, in December 2019, shares genomic structural similarities with the severe acute respiratory syndrome coronavirus (SARS-CoV). 30,000 UK deaths have occurred due to Covid-19.
It is believed that kidney transplant recipients have a high infection risk due to long-term immunosuppression and comorbidities. Covid-19 is associated with diffuse lung involvement, respiratory failure and increased mortality, and the data available in patients receiving kidney transplant is limited. This study is demonstrate 8 kidney transplant recipients who developed covid-19 post kidney transplantation.
Patients profile:
Treatment:
Conclusion:
Level of evidence: Level 4, case series
Impact factor of a journal: is the frequency by which an article in a journal has been cited in a particular period of time, which in turn reflect the potency and importance of the journal. the impact factor of a journal is calculated by dividing the number of current year citations to the source items published in that journal during the previous two years.
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
Nephron 2021
Clinical presentation:
Management included
Conclusion and recommendations
Each patient should be evaluated and categorized to 3 main categories:
Mild case with normal chest Xray and mild clinical symptoms maintaining saturation on room air no modifications or just half dose of MMF maybe needed
Moderate cases with abnormal chest Xray need stoppage of MMF and close monitoring
Sever cases with high oxygen requirement need careful assessment with considering possibility of mixed bacterial, fungal infections and cytokine storm.
Impact factor:
measurement of journal citation frequency in a particular year, it calculated dividing number of articles citing by total number of articles.
I. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
Summarise this article.
Introduction
– kidney transplant recipients (KTRs) are thought to have a high risk of infection due to the long-term immunosuppressive therapies and associated comorbidities
Case reports
– 8 cases of KTRs infected with COVID-19 disease
– 4 males, 4 females
– median age 48.5years, range 21-71 years
– 3 patients had been transplanted within the last 3 months, the rest were transplanted for more than 1 year
– hypertension was the most frequently associated comorbidity
– most common presenting features were cough and fever
– portable chest radiograph was the main radiological investigation
– five out of the 8 cases had bilateral patchy consolidation on CXR
– other common features include: high CRP, lymphopenia, high ferritin level
– 1 patient was managed as an outpatient while 7 patients required hospital admission, 1 of them was referred to ICU for further treatment including mechanical ventilation and CVVH, incidentally this patient had aspergillosis on BAL
– 2 developed AKI
– all patients apart from 1 were on tacrolimus, mycophenolate, prednisone – the patient was on tacrolimus, azathioprine and prednisone
– management entailed: – supportive therapy with IVF, monitoring kidney function, symptomatic treatment with oxygen depending on the oxygen saturation, discontinuation of antiproliferative immunosuppressive agents
– 7 patients recovered and were discharged for self-isolation at home
– short hospital stay with home-based self-isolation on discharge reduces the burden on the healthcare system and also protects the staff and the public
Discussion
– risk factors for infection in kidney transplant patients: immunosuppression, associated comorbidities (hypertension, diabetes, COPD, malignancies), underlying CKD
– high CRP could be linked to unfavourable outcomes like ARDS, myocardial injury, death
– high serum ferritin was also associated with ARDS and death so was interleukin 6 (IL-6)
– use of chest CT scan in the COVID-19 era put a significant burden on the radiology department and also made infection control a challenge
– use of portable chest radiographs should therefore be considered to reduce infection transmission
– management involves withdrawal of the antiproliferative drugs and offering supportive treatment
– overall, the management in KTRs depends on the age, severity of infection, associated comorbidities, post-transplant duration, rejection episodes, tissue mismatch
– for mild infections, the common practice is to continue or reduce the dose of immunosuppressive drugs while monitoring the patient closely
– for severe infections, consider stopping the antiproliferative agents
– in severe cases requiring mechanical ventilation, in addition to stopping antiproliferative agents, the CNIs can be withdrawn but usually the corticosteroids are maintained
– individualized treatment is usually advocated for based on thorough assessment of the patient
– there was no evidence to support use of Tocilizumab (IL-6 blocker) in management of COVID 19 in both transplant and non-transplant patients
– the efficacy of convalescent plasma i.e., blood derived from recovered patients was questionable
– the results from the use of lopinavir and ritonavir were also discouraging
– Remdisivir was approved by FDA as viable treatment option for hospitalized COVID-19 patients
Conclusion
– the clinical presentation of COVID-19 in transplant patients is similar to that of the general population where cough and fever were the most frequent symptoms
– supportive treatment plays a critical role in the management of COVID-19 patients
– CT Chest can be avoided by focusing on simple bedside measures like oxygen saturation and portable CXR
– short hospital stay and home-based self-isolation reduces the burden on the health system as well as protects the staff and the public from the infection
– Remdesivir should only be used in a setting where CNI drug level monitoring can be done
Level of evidence provided by this article
Level IV
What is meant by the impact factor of a journal? (1)
– Impact factor (IF) of a journal is a measure of the frequency by which the average article in a journal has been cited in a particular time period i.e., the number of times an average article in a journal is cited during a year
– IF evaluates the relative importance of a journal within its field
Reference
1. Sharma M, Sarin A, Gupta P, Sachdeva S, Desai AV. Journal impact factor: its use, significance and limitations. World journal of nuclear medicine. 2014 May;13(2):146. PubMed PMID: 25191134. Pubmed Central PMCID: PMC4150161. Epub 2014/09/06. eng.
The RECOVERY trial has found that:
In review of RECOVERY trial results cases 5 and 8 could have received recommended additional medications:
Patient 1 got IV fluids and paracetamol. MMF was discontinued she was discharged after 2 days.
Patient 2 received IV fluid and symptomatic treatment. He was discharged 2 days after MMF was discontinued.
Patient 3 was advised to drink plenty of fluids. MMF was discontinued; Tacrolimus dose was reduced.
Patient 4 was given paracetamol. MMF was discontinued; Tacrolimus dose was increased.
Patient 5 needed temporary CVVH and intubation. MMF was discontinued. Recovery may have been faster if Baricitinib and/or Tocilizumab had been used.
Patient 6 was admitted for adequate hydration and symptomatic treatment. MMF was discontinued.
Patient 7 had MMF discontinued; Paracetamol and IV fluids were administered. Then discharged after 4 days.
Patient 8 Management included discontinuation of azathioprine, reduction of tacrolimus dose, and increase of prednisolone dose. Dexamethasone could have been considered instead of prednisolone.
Case Reports
Patient 1: a 21-year-old female – who had a deceased donor kidney transplant in December 2019 presented on March 30 with fever (39.2°C).
The chest X-ray was clear, and kidney function tests were stable
His immunosuppressive drugs were prednisolone 5 mg OD, tacrolimus, and MMF 500 mg BD.
Patient 4: a 63-year-old male with a history of IgA nephropathy with a deceased donor kidney transplant in December 2005
He is hypertensive and maintained on calcium channel blockers.
Patient 5: A 47-year-old female with bronchial asthma received a deceased donor kidney transplant in December 2019
She was maintained on prednisolone 5 mg OD, tacrolimus with levels between 5 and 7 ng/mL, and MMF 250 mg BD.
Patient 6: A 71-year-old female with type II diabetes, received deceased donor kidney transplantation in November 2015
Her immunosuppressive therapy included prednisolone, tacrolimus, and MMF.
Patient 7: A 40-year-old female with hypertension received deceased donor kidney transplantation in June 2017
She is maintained on prednisolone, tacrolimus, and MMF.
Patient Age/sex Tx date Comorbidities Fever Respiratory involvements Renal involvements
Baseline immunosuppression
2 71/M Feb 2016 Hypertension and post-Tx malignancy No Dry cough No Pred-Tac-MMF. 5 47/F Dec 2019 Bronchial asthma, aspergillosis No Dry cough + SOB AKI Pred-Tac-MMF.
2 71/M Feb 2016 Hypertension and post-Tx malignancy No Dry cough No Pred-Tac-MMF.
5 47/F Dec 2019 Bronchial asthma, aspergillosis No Dry cough + SOB AKI Pred-Tac-MMF.
COVID-19, coronavirus disease 2019; F, female; M, male; Tx date, date of transplant; post-Tx, post-transplant; DM, diabetes mellitus; SOB, shortness of breath; Pred, prednisolone; Tac, tacrolimus; MMF, mycophenolic acid; Aza, azathioprine
Discussion
We present our experience with 8 cases of COVID-19 infection in kidney transplant patients from Sheffield Kidney Institute, UK.
Three patients had kidney transplantation within the last 3 months, and the rest were transplanted for more than a year.
One of our 8 patients was managed as an outpatient and advised to self-isolate at home, with the remaining 7 requiring hospital admission.
One patient required ITU admission, where she needed mechanical ventilation.
Bronchoalveolar lavage of this patient confirmed aspergillosis for which she is receiving antifungal treatment.
The other 6 patients received supportive therapy on the renal ward.
Transplant patients are at a high risk of infection due to multiple risk factors, including immunosuppression, underlying CKD, and associated comorbidities, especial-
Findings
Guan et al, reported that 83.2% of infected patients had lymphopania on admission
Color version available online
Many studies discussed the outcome of such comorbidities in COVID-19 patients.
These studies reported that hypertensive and diabetic patients have a double-fold risk of infection, while COPD patients have a 5-fold risk.
Liang et al, reported that 1% of COVID-19 patients had a history of malignancy, which was higher than the prevalence of cancer in the overall Chinese population (0.29%).
In cases of AKI associated with SARS and MERS, continuous renal replacement therapy showed promising results .
Many studies showed that COVID-19 infection is associated with high CRP..
The US Food and Drug Administration investigate the efficacy of convalescent plasma as a treatment option for patients with severe COVID-19 infection.
Drug Administration has authorized the use of remdesivir as a treatment option for hospitalized COVID-19 patients.
Conclusion
The presentations of COVID-19 infected renal transplant patients were not different from the general treatment where fever and cough were the most frequent symptoms.
We believe that our transplant patients did not behave differently from the general population as far as COVID-19 infection is concerned.
Supportive treatment could be sufficient or at least to be tried first.
It is worth mentioning that the clinical examination supported by simple bedside measures such as oxygen saturation and portable CXR rather than.
We found that short hospital stay with self-isolation on discharge reduces the burden on the health services and protect the staff and the public.
Since remdisivir was approved for the treatment of COVID-19 and its interaction with CNI is yet unknown, we recommend treatment with remdisivir in a hospital setting where CNI drug level monitoring is available
Level of evidence 5
impact factor of a journal
An academic journal’s impact factor is a scientometric index that is used to assess how important the journal is compared to others in its field.
The annual mean number of citations of articles published in the previous two years in a particular publication is reflected in the impact factor.
Summary of the article
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
This is a case series analysis of eight KTRs with COVID-19 infection.
The common features of COVID-19 in KTRs of these cases were :
1. Fever and cough are the most common presenting feature.
2. Lymophopenia, high C-reactive protein, and a very high ferritin level.
3. HTN is the most common associated co-morbidity.
4. Two patients had AKI, one of them required continuous veno-venous hemofiltration.
The therapeutic strategies for managing these KTRs with COVID-19 infection were as follows:
1. Antiproliferative immunosuppressive drugs were discontinued for all patients.
2. An outpatient management and advised to self-isolate at home(1 patient).
3. Hospital admission and supportive therapy on the renal ward (intravenous fluid therapy, monitoring renal function, and symptomatic treatment with or without ward-based oxygen therapy based on the oxygen saturation)(6 patients).
4. ITU admission and mechanical ventilation(1 patient).
5. Continuous Veno-Venous Hemofiltration-CVVH (1 patient; ITU admission+ mechanical ventilation and CVVH).
Discussion:
1. Early studies reported that the incidence of AKI was low (3–9%).
2. Recent studies(Cheng et al) showed a higher frequency of renal abnormalities among 710 patients:
· 44% had proteinuria.
· 26.7% had haematuria.
· 14.1% had high serum Cr.
3. The pathophysiology of renal involvement is still unclear, but theories suggest:
· A cytokine storm syndrome.
· Direct renal injury by the virus.
4. Diagnosis and laboratory features of COVID-19 infection:
· Low lymphocyte/white blood cell ratio had fatal outcomes.
· High CRP(60.7%) is linked to unfavorable outcome; ARDS, myocardial damage and death.
· Higher serum ferritin is associated with ARDS development and death.
· High IL-6 levels (52% ); a novel biomarker for COVID-19 diagnosis and can be associated with an increased risk of mortality.
· CXR my show patchy consolidation.
· CT when there is high suspicion with normal or uncertain appearance of CXR in a seriously ill patient.
5. Management of COVID-19 infection:
A. Mild infections: the usual practice is to continue or reduce the dose of immunosup- pressive drugs. Discontinuation of the antiproliferative drugs is suggested.
B. Severe infection with requirement to mechanical ventilation: to maintain corticosteroids, hold antiproliferative and to argue about ceasing CNIs.
C. Remdesivir-treated patients had 31% faster time to recovery when compared to control.
D. CRRT may play a role in the management of AKI in COVID-19 patients. It was assumed that high-volume hemofiltration could remove inflammatory cytokines (tumour necrosis factor, IL-6, and IL-1β) involved in the pathogenesis of renal injury.
The level of evidence provided by this article:
This is a case series study with level of evidence grade 5.
The impact factor of a journal:
The Impact factor (IF) or journal impact factor (JIF) is a sciento-metric index calculated by Clarivate that reflects the yearly mean number of citations of articles published in the last two years in a given journal, as indexed by Clarivate’s Web of Science.
Limitations of the JIF
· Some journals increased the impact factor value by reducing the number of scholarly records.
· Extension of the impact factor to the assessment of journal quality or individual authors is inappropriate.
· Extension of the impact factor to cross-discipline journal comparison is also inappropriate.
· Those who choose to use the impact factor as a comparative tool should be aware of the nature and premise of its derivation and also of its inherent flaws and practical limitations.
Introduction:
The new coronavirus disease 2019 (COVID-19) infection emerged in Wuhan city, China in December 2019 . By April 26, 2020, 203,818 reported deaths worldwide and mortality cases exceeded 30,000. There is a common belief that kidney transplant recipients have a high risk of infection due to long-term immunosuppression and associated comorbidities.8 cases of kidney transplant recipients infected with COVID-19 were reported .
Case report and discussion :
This report discusses 8 cases of COVID-19 infection in kidney transplant patients from Sheffield Kidney Institute, UK, with median age 48.5 years ,4 males and 4 females .
All 8 patients were receiving prednisone and tacrolimus, 7 patients were receiving mycophenolate mofetil, and 1 patient was receiving azathioprine. Six patients had multiple comorbidities (4 had hypertension, 1 had type II DM,1 had bronchial asthma and aspergillosis, and 1 had a history of cancer).
In this case series, the most frequent presentation was fever (5 patients) and cough (5 patients). Fever was reported to be the most common symptom followed by cough . Two large studies demonstrated that 82-87% of their patients had a fever, while patients with cough ranged from 44 to 65. Two of our patients had AKI (cases 4 & 5); 1 of them required renal replacement therapy in the form of CVVH (case 5). Early studies reported that the incidence of AKI was low (3-9%) in those with COVID-19 infection, but recent studies showed a higher frequency of renal abnormalities.
Low lymphocyte/white blood cell ratio and high CRP are associated with fatal outcomes, while serum ferritin is associated with ARDS development and death. IL-6 is considered a novel biomarker for COVID-19 diagnosis, but is not routinely measured. The role of IL-6 blocker (tocilizumab) in treatment of COVID-19 in both transplant and non-transplant population was found in 7 patients, five of whom had bilateral patchy consolidation and 2 who had no classical changes.
CT decontamination may disrupt service availability and portable chest X-ray should be considered to reduce transmission. The British Society of Thoracic Imaging (BSTI) issued guidelines which state that CT should not be used unless there is high suspicion of CXR in a seriously ill patient.
Managing immunosuppression in kidney transplant recipients should be individualized based on the patient’s age, severity, post-transplant duration, comorbidity, tissue mismatch, and any episodes of rejection.
Conclusion :
The presentations of COVID-19-infected renal transplant patients were similar to the general population, with fever and cough being the most frequent symptoms. Supportive treatment should be tried first, and short hospital stays with self-isolation on discharge reduce the burden on the health service and protect the public.
?What is the level of evidence provided by this article
level IV (Case series )
?What is meant by the impact factor of a journal
The impact factor of an academic journal is a scientometric index which is used to evaluate the relative importance of a journal within its field. The impact factor reflects the yearly mean number of citations of articles published in the last two years in a given journal.
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
Summary:
· Cases with COVID 19 infection, were included (most common symptom was fever and cough, with hypotension as comorbidity). All had lymphopenia, high CRP and ferritin levels. Diagnosis was confirmed by nasal/throat swab for COVID 19 RNA. CXR was either normal or showing bilateral infiltration suggestive of viral pneumonia.
· KTR are at higher risk of infection due to IS therapy, CKD condition and other comorbidities as hypertension or DM.
· 2 cases presented with AKI (one case required CVVHF), the mechanism of renal involvement ay be either direct viral invasion or involvement as a part of cytokine storm. So, CVVH may help by removing circulating cytokines as TNF alfa, IL -1 and IL-6.
· Supportive treatment with oxygen, antipyretic (paracetamol) and IV fluid therapy with early discharge to home isolation was better to decrease the burden, cost and infections among health care workers.
· All patients were informed to drink plenty of fluids and to report any new symptoms to the hospital.
· Discontinuation of antiproliferative MMF was done in all hospitalized cases.
· Higher levels of CRP and severe lymphopenia were linked to development of ARDS and worse prognosis.
· Although IL-6 is a new marker for COVID 19 diagnosis, no clear evidence to support its diagnostic or prognostic role (so not done routinely in all cases and also the role of IL-6 blocker (tocilizumab) is not clear.
· CXR should be 1st imaging modality in suspected COVID cases to avoid burden on CT and uncontrollable spread of infection.
· Still, case series research cannot provide clear guidelines for management, but the current article can suggest that:
o In mild cases, reduction or stoppage of antiproliferative (MMF/ AZA).
o In severe /ventilated cases: consider CNI stoppage and keep or even slight increase in steroids dose.
o Individualized therapy according to severity of infection, comorbid condition, time since transplantation all can play a role in management plan.
o Convalescent plasma derived from recovered cases is still questionable if it has value for severe cases.
o None of the included cases received antiviral therapy.
o RCTs showed that combination of lopinavir and ritonavir among SARS-CoV patients has no value (discouraging results).
o While remdesivir-treated patients had 31% faster time to recovery when compared to control, so may be a promising treatment option in hospitalized cases with close monitoring of CNI level.
Level of evidence: case series is level 4
Meaning of journal impact:
· is a term used to evaluate the relative importance of a journal in a particular field of science. It is derived from the frequency of citation of its articles in a particular period of time.
· Journals with much publication of review articles will have higher impact factor.
The RECOVERY trial has found that there are other treatment options that were effective in COVID 19 treatment as: For COVID-19
Dear All
You have noticed that I published this article before the publication of the results of the RECOVERY trial. Do you think I would have treated these patients differently?
I would love to see the response of our colleagues, fellows on this forum, to the above mentioned question.
Thank you Professor Halawa for the question
In the majority of the trials of COVID 19 therapeutic, solid organ transplant recipients were not included. Most of the data comes from retrospective studies where these therapeutic agents were used in SOT recipients.
Tocilizumab has been evaluated in observational studies. In a study by Perez-Saez et al, the SOT recipients who received Tocilizumab had a higher mortality rate of 32.5% which was significantly higher that in the SOT recipients in earlier studies. This was postulated to be due to the higher baseline inflammatory markers in the SOT recipients. In a matched cohort study of 117 SOT recipients, 29 patients received tocilizumab compared to matched controls and no benefit in mortality was found. This study noted an increase in secondary infections in the tocilizumab group.
The NIH and the American Society for Transplantation recommend the use of baricitinib in SOT recipients with severe/critical COVID 19 disease with rapid progression
Stopping the anti-metabolite and supportive care still remain the gold standard for treatment of COVID 19 in SOT recipients
Baricitinib could be used in critical/severe COVID 19 disease
In This case series, there was only one patient who required mechanical ventilation – case 5. And this was due to aspergillosis. So I don’t think that any of the newer therapies would have made a difference in this cohort of patients
The RECOVERY trial has found that there are other treatment options that were effective in COVID 19 treatment as:
sotrovimab (a monoclonal antibody treatment against the spike protein)
molnupiravir (an antiviral treatment)
paxlovid (an antiviral treatment)
In addition, use of high dose dexamethasone ( 6mg once daily for 10 days or until discharge in hospitalized patients requiring oxygen (with or without non-invasive ventilation) and for patients on invasive mechanical ventilation or extra-corporeal membranous oxygenation (ECMO). As a consequence, dexamethasone 6 mg once daily is now widely recommended for treatment of such patients.
I think addition of dexa can be used for the case who required MV and CVVHF. Also use of new available drugs is worthy trying in severe cases as case with CVVH.
While in rest of cases with short hospitalization, I think no added treatment was required and (supportive therapy and stoppage of antiproliferative therapy remains the golden standard for managemnt )
_ also, tocioizumab was found to be non effective and increased mortality among SOT.
Dear Prof. Ahmad:
You have noticed that I published this article before the publication of the results of the RECOVERY trial. Do you think I would have treated these patients differently?
Yes; in the followings:
(1) in the form of severe disease with cytokine storm you might give dexamethasone 6 mg for 10 days, with subsequent tapper down .
(2) Introduction of remdsivir early in the treatment of your patients.
(3) in severe case you might give Tocilizumab/ or baricitinib.
but the main stay of treatment would not differ in the form of supportive measures, immunosuppressive reduction/ or discontinuation
Thnxs prof,
Thank you prof Ahmed Halawa
The recovery trial found that the use of dexamethasone in patients hospitalized with Covid-19, resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support.
They found that also tocilizumab reduces the risk of deaths in patients hospitalized with severe COVID-19 infection, it shortens the time taken for patients to be successfully discharged from hospital, and reduces the need for a mechanical ventilator.
The RECOVERY team also found that treatment with baricitinib reduced deaths by 13%. It also reduced the chance of progressing to invasive mechanical ventilation.
In this case series the treatment will not be different because all patients were mild to moderate cases except case number 5 who deteriorates and found to have aspergellosis and managed without specific antiviral , other wise all underwent supportive therapy ,reduction of immunosuppression stop antimetabolites and reduce the dose of tacrolimus .
RECOVERY had demonstrated 4 life-saving drugs including – dexamethasone, tocilizumab, baricitinib and casirivimab-imdevimab . In each case, results from RECOVERY were clear enough to rapidly influence global practice due to it’s particular setting in the UK during the SARS-CoV-2 pandemic also due to it’s generalisable contexts.
Reference
Leon Peto, Peter Horby, Martin Landray,Establishing COVID-19 trials at scale and pace: Experience from the RECOVERY trial,Advances in Biological Regulation,Volume 86,
2022,100901,
ISSN 2212-4926,
RECOVERY study as shown in attached figure there are another 4 drugs options including – dexamethasone, tocilizumab, baricitinib and casirivimab-imdevimab can be used in critically ill COVID patients.
in this article you discussed 8 cases
Only case 5 i think she may get benefits from Tocilizumab specially with high Serum interleukin-6 22.2 pg/mL (n = 0–7 pg/mL) but with good cover of antifungal and antimicrobial therapy.
The other 7 cases are considered mild to moderate cases and managment in the form of hold MMF and supportive management were excellent with outstanding outcomes.
Professor, COVID-19, unlike Influenza and other viral diseases, is a disease that courses with systemic vasculitis, including pulmonary vasculitis with evolution to Acute Respiratory Syndrome.
Withdrawing Mycophenolate is an excellent strategy to minimize immunosuppression to face the active viral disease and, consequently, the vasculitis process that it develops.
For Th2-response diseases and with vasculitic inflammatory disease, corticosteroids have always been a strategy to control the disease. The dose is dependent on the evolution and severity of the patient.
His vast knowledge of pathophysiology and the immune process of transplantation naturally led him to modulate the patient appropriately.
The RECOVERY Trial has found four treatments that are effective for severe COVID-19 dexamethasone, tocilizumab, baricitinib and casirivimab-imdevimab.
In this article, among 8 cases, only case 5 might get benefits from Tocilizumab as high IL-6 level in a critically ill patient. Though this patient recovered with out those emerging treatment options.
In these cases 7/8 results from recovery trial would have no impacts on its management, so all the supportive care provided was enough.
Regarding 1/8 in ICU patient would have received DEXA according to recovery trial..
Thank you Prof. A .Halawa
Thank you for the question, Prof.
In these all cases except one would have no change in its management.
Regarding one case in ICU patient would have received dexamethasone according to recovery trial.
I think yes especially in those cases which deteriorated. but not really in those who recovered with 2-4 days as they were mild cases.but adding dexamethasone to those which deteriorated would have helped faster recovery.
Prof I think only one patient which needed mechanical ventilation could have been treated differently ( use of dexa). In view of RECOVERY trial as such patients showed reduce mortality , rest of the patients had mild to moderate disease with no oxygen requirement and can be managed same way as u did .
Remdesivir is another thing which can be considered in these patients
Thank you Professor.
Except patient 5 and 8 (requiring respiratory support), the treatment would remain same. Those 2 patients would have been given dexamethasone.
the conclusion of recovery trial was :In patients hospitalized with Covid-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support.
accordingly sever COVID 19 infected patient may get benefit from dexamethasone treatment.
I do not think so since supportive therapy with IVF, monitoring kidney function, symptomatic treatment with oxygen depending on the oxygen saturation, reduction/ discontinuation of antiproliferative immunosuppressive agents seemed to work well for most patients apart from the one with severe disease who might have benefited from IV dexamethasone 6mg OD.
With exception of the ICU pt where dexamethasone would have been used ,the rest of the mgt would not have changed with results of the recovery trial.
THANKS PROF HALAWA
I do not think so since supportive therapy with IVF, monitoring kidney function, symptomatic treatment with oxygen depending on the oxygen saturation, reduction/ discontinuation of antiproliferative immunosuppressive agents seemed to work well for most patients apart from the one with severe disease who might have benefited from IV dexamethasone 6mg OD.
Thanks prof
In RECOVERY trial showed that there is no benefit of remdisivir on reduction of mortality, only reduce period of hospitalization and dexamethasone reduce mortality those require oxygen.
In your study, you recommend remdisivir in hospital setting which is similar to RECOVERY trial.
IntroductionThe coronavirus disease 2019 (COVID-19) was an infection that led to a pandemic. It emerged in Wuhan city, China in December 2019. Kidney transplant recipients have a high risk of infection due to immune suppression and associated comorbidities. This report summarizes cases of kidney transplant recipients that were infected with COVID-19.
Case reportsPatient 1
A 21-year-old female had a kidney transplant in December 2019 from a deceased donor. She presented on March 30 with fever and lethargy. She had no respiratory symptoms and clinical examination was unremarkable apart from the fever. The chest x-ray was also clear she tested positive for COVID-19. She is hypertensive and usually maintained on calcium channel and beta blockers. Her regular immune suppression medications included prednisone, tacrolimus and mycofenolate mofetil (MMF). During admission she received supportive medical management and MMF was discontinued. She was discharged after two days with full recovery and stable kidney functions.
Patient 2A 71-year-old male with hypertensive nephropathy on calcium channel blockers and he received a kidney transplant in February 2016. He had a history of colon adenocarcinoma in 2019. His regular immune suppression medications included prednisone, tacrolimus and MMF. He presented on April 2, 2020 with a dry cough and stable vital signs his chest x-ray revealed battery bilateral consolidation and he was tested positive for COVID-19. His MMF is also discontinued and he received supportive IV fluids and symptomatic treatment. He was discharged two days later with stable kidney functions.
Patient 3A 50-year-old male underwent life donor kidney transplant in February 2020 due to a history of Wegner’s granuloma. His regular immune suppression medications included prednisone, tacrolimus and MMF. He presented on April 3 with a productive cough and was tested positive for COVID-19 infection. His chest xray was clear and kidney function tests were stable. His management also included discontinuation of MMF, reduction of tacrolimus dose and self isolation at home. He did not present with any further symptoms.
Patient 4Hey 63-year-old male with a history of IgA nephropathy, received a deceased donor kidney transplant in December 2005. He is also hypertensive on calcium channel blockers. He presented on March 20 with fevers and acute kidney injury. The chest x-ray showed bilateral consolidation. The patient tested positive for COVID-19 infection, and blood culture was positive for staphylococcus aureus. His regular immune suppression medications included prednisone, tacrolimus and MMF. The patient required admission and received IV antibiotics and paracetamol. MMF was stopped and the tacrolimus doors was increased. The patient recovered, and an improvement of kidney function was noted.
Patient 5A 47 year old female with bronchial asthma received a deceased donor kidney transplant in December 2019. Her regular immune suppression medications included prednisone, tacrolimus and MMF. She presented in April with a dry cough and shortness of breath. Her chest x-ray showed bilateral middle and lower zone consolidation. She was tested positive for COVID-19 infection and acute kidney injury. Her urine culture was positive for E. coli infection, and her blood culture was negative. The patient’s respiratory function deteriorated, and she required invasive ventilation. Bronchoalveolar lavage showed growth of aspergillus. She required antibiotics and antifungals. Her MMF was discontinued, her kidney functions deteriorated and she became anuric. She required CVVH. She was weaned of mechanical ventilation after 14 days and transferred to the medical ward. Her kidney functions gradually improved. She was discharged home and CVVH was discontinued.
Patient 6A 71-year-old female with type two diabetes received a deceased donor kidney transplantation in 2015. Her regular immune suppression medications included prednisone, tacrolimus and MMF. She presented in April with a fever and no other complaints her chest x-ray showed bilateral peripheral mid and lower zone consolidation. She was tested positive for COVID-19 infection. She was admitted for hydration and symptomatic treatment. MMF was discontinued. She was discharged after four days with full recovery.
Patient 7A 40 year old female with hypertension, received a deceased donor kidney transplantation in 2017. Her regular immune suppression medications included prednisone, tacrolimus and MMF. She was also amlodipine for her hypertension. She presented in April with a fever and dry cough. She was tested positive for COVID-19 infection. MMF was discontinued paracetamol and fluids were administered and she was discharged after four days with full recovery.
Patient 8A 38 year old male with a failing kidney transplant in 2013 presented with a productive cough and shortness of breath for two days. His regular immune suppression medications included prednisone, tacrolimus and azathioprine. He was tested positive for COVID-19 infection. His kidney function test remained unchanged. His chest x-ray revealed bilateral infiltrates. And his management included discontinuation of azathioprine, reducing tacrolimus dosage and increasing prednisone. He did not require dialysis. Oxygen saturation improved and he was discharged after two days.
DiscussionEight cases were summarized in this review. The review included patients with kidney transplant who got infected with COVID-19. The median age of the patients was 48.5 years. There were four males, and four females. Three patients had kidney transplantation within the last three months of the review and the rest of the patients had been transplanted for more than a year.
The most common initial symptoms were fever and cough. All 8 patients were on tacrolimus and prednisone. 7 patients were on mycophenolate and one patient was on azathioprine. In all the patients the antimetabolite was stopped. No patients received any antiviral agents. All 8 patients recovered.
The one patient that required mechanical ventilation was also infected with fungal infection.
Transplant patients are at a high risk of infection, due to immune suppression, chronic kidney disease, associated comorbidities which include diabetes and hypertension.
When managing immunosuppression in post-transplant patients the age, duration of transplant, rejection of episodes and the severity of the COVID infection needs to be taken in to account. Every patient needs to be individualized.
In general, for mild infections, the usual practice is to continue or reduce the dose of immune suppression. Since the review only looked at eight patients, they are unable to provide recommendations. The treatment should be individualized based on the assessment of each patient.
ConclusionIn this report, the presentation of COVID-19 infection in renal transplant patients was not different from that of the general population. The transplant population did not behave differently from the general population in the duration of the COVID-19 infection. Due to the small sample size it was difficult to evaluate the effect of immune suppression during the course of the disease.
Level of Evidence: This is a case series so this is level IV
Impact Factor of A Journal:
This is a scientometric index calculated by clarivate the calculates the yearly mean number of citations of articles published in the previous 2 years.
It is used to measure the importance or rank of a journal by calculating the number of times its articles are cited
Thank you, I appreciate your effort
Please summarise this article. 8 cases of COVID-19 in kidney transplant Sheffield Kidney experience reports .
The median age of patients was 48.5 years
4 males and 4 females.
Three patients had kidney transplantation within the last 3 months, and the rest were transplanted for more than a year.
The most common initial symptoms were fever (5 patients) and cough (5 patients).
All 8 patients were receiving prednisone and tacrolimus, 7 patients were receiving mycophenolate mofetil, and 1 patient was receiving azathioprine.
Two patients had AKI 1 of them required continuous veno-venous hemofiltration
Blood results all patients had lymphopenia and high CRP. Three patients had elevated serum ferritin, and 1 patient had high serum interleukin-6 (IL-6).
A portable chest X-ray was performed in 7 patients, which was clear in 2 of them, and the rest had a picture consistent with viral pneumonia.
One of our 8 patients was managed as an outpatient and advised to self-isolate at home, with the remaining 7 requiring hospital admission.
One patient required ITU admission, needed mechanical ventilation Bronchoalveolar lavage of this patient confirmed aspergillosis receiving antifungal treatment . Another patient required ward-based oxygen therapy The other 6 patients received supportive therapy on the renal ward (intravenous fluid therapy, monitoring renal function, and symptomatic treatment
Antiproliferative immunosuppressive drugs were discontinued for all patients.
studies Facts /hints
Transplant patients are at a high risk of infection due to multiple risk factors, including immunosuppression, underlying CKD, and associated comorbidities
hypertensive and diabetic patients have a double-fold risk of infection, while COPD patients have a 5-fold risk.
Liang et al. reported that 1% of COVID-19 patients had a history of malignancy,the most frequent tumour was lung cancer
the incidence of malignancy was 0.9% among their reported COVID-19 patients
Two large studies demonstrated that 82–87% of their patients had a fever, while patients with cough ranged from 44 to 65.7%
Early studies reported that the incidence of AKI was low (3–9%) in those with COVID-19 infection However, recent studies showed a higher frequency of renal abnormalities.
Cheng et al. reported that among 710 patients, 44% had proteinuria, 26.7% had haematuria, and 14.1% had high serum Cr.
The pathophysiology of renal involvement is still unclear, but theories suggest a cytokine storm syndrome or direct renal injury by the virus. Scientists succeeded in isolating SARS-CoV-2 from a urine sample of an infected patient, suggesting the kidney can be a target of this virus
cases of AKI associated with SARS and MERS, continuous renal replacement therapy was assumed that high-volume hemofiltration could remove inflammatory cytokines (tumour necrosis factor, IL-6, and IL-1β) involved in the pathogenesis of renal injury
Guan et al.reported that 83.2% of infected patients had lymphopenia on admission. Another study suggested a link between lymphopenia and acute respiratory distress syndrome (ARDS) development
Guan et al. reported that 60.7% of patients had an elevated CRP, while severe cases had a higher level compared to the non-severe ones (81.5 vs. 56.4% for CRP).
Many reports suggested that higher serum ferritin is associated with ARDS development and death
IL-6 is considered a novel biomarker for COVID-19 diagnosis.
.Chen et al. reported that 52% (51/99) of patients had high IL-6 levels on admission. Other studies suggested that increased IL-6 levels can be associated with an increased risk of mortality . Since we are not sure about the sensitivity and the specificity of IL-6, we did not measure it routinely. Also, there is no clear evidence to support the role of IL-6 blocker (tocilizumab) in treatment of COVID-19 in both transplant and non-transplant population.
The Italian and British hospitals employ chest X-ray as a first-line triage tool as the results of COVID-19 testing may take more time
The British Society of Thoracic Imaging (BSTI) issued guidelines which state that there is no recommended use of CT unless there is high suspicion with normal or uncertain appearance of CXR in a seriously ill patient
in mild infections,reduce the dose of immunosuppressive drugs. suggest discontinuation of the antiproliferative drugs (azathioprine and mycophenolate mofetil) while monitoring the patients closely.
In severe cases requiring mechanical ventilation, we can argue about ceasing calcineurin inhibitors while maintaining corticosteroid therapy. Undoubtedly, the treatment should be individualized based on the careful assessment of each patient.
the US Food and Drug Administration has authorized the use of remdesivir as a treatment option for hospitalized COVID-19 patients
What is the level of evidence provided by this article?
Grade of Recommendation c
Level of Evidence 4
What is meant by the impact factor of a journal? is an index that measures how often a journal’s articles are cited in other research. This is calculated by the number of citations received by articles published in that journal during the two preceding years, divided by the total number of articles published in that journal during the two preceding years. You can find the journal Impact Factor on the journal homepage.
Thank you, I appreciate your effort
Summarise this article.There is a common belief among transplant clinicians that kidney transplant recipients have a high risk of infection due to long-term immunosuppression and associated comorbidities. This short series demonstrates experience in managing COVID-19 disease in renal transplant patients in the absence of strong evidence.
8 cases of kidney transplant recipients infected with COVID-19
median age = 48.5 years; range = 21–71 years
4 males and 4 females
The most frequently associated comorbidity was hypertension.
The most common presenting features were fever and cough.
The main radiological investigation was a portable chest X-ray.
Other common features included lymphopenia, high C-reactive protein, and a very high ferritin level.
Overall, 1 patient was managed as an outpatient, the remaining 7 required hospital admission, 1 of them referred to the intensive therapy unit.
Management included intravenous fluid therapy, monitoring renal function, and symptomatic treatment with or without ward-based oxygen therapy depending on oxygen saturation
Discontinuation of the antiproliferative immunosuppressive drugs.
Seven patients recovered and discharged home to self-isolate.
One patient required intensive care treatment and mechanical ventilation.
Non had antiviral treatment
Discussion
Transplant patients are at a high risk of infection due to multiple risk factors, including immunosuppression, underlying CKD, and associated comorbidities.
Hypertensive and diabetic patients have a double-fold risk of infection, while COPD patients have a 5-fold risk.
The pathophysiology of renal involvement is still unclear, but theories suggest a cytokine storm syndrome or direct renal injury by the virus. Continuous renal replacement therapy may play a role in the management of AKI in COVID-19 patients.
Lymphopenia, High CRP and Ferritin levels are associated with ARDS and poor outcomes.
No clear evidence to support the role of IL-6 blocker (tocilizumab) in treatment of COVID-19 in both transplant and non-transplant population.
It is also essential for clinicians of all specialities to be familiar with the radiological findings of COVID-19 on chest X-ray
Discontinue the antiproliferative drugs (azathioprine and mycophenolate mofetil) while monitoring the patients closely.
In severe cases requiring mechanical ventilation, stop calcineurin inhibitors while maintaining corticosteroid therapy
Conclusions
Presentations of COVID-19 infected renal transplant patients is not different from the general population
Supportive treatment could be sufficient or at least to be tried first
Short hospital stay with self-isolation on discharge reduces the burden on the health service and protect the staff and the public
Thank you, I appreciate your effort
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current EvidenceSummarize the article.
COVID 19 IN RENAL TRANSPLANT RECIPIENTS;CASE SERIES AND A BRIESF REVIEW OF CURRENT EVIDENCE.
Introduction.
Case reports;
Discussion.
-Fever and cough were the most prominent symptoms for Covid in the listed cases.
-Aspergillosis is a potential complication in this cohort and can contribute to poor outcomes if not addressed.
-Multiple comorbidities in transplant pts increases risk of infection.
-The role of CRRT to decrease inflammatory cytokines can be explored in AKI cases with good outcomes in Covid pts with AKI.
-Lymphopenia and high CRP on admission has poor outcomes post covid, Ferritin is an acute phase reactant not sensitive and specific as a prognostic marker.
-More studies needed on IL6 as a novel marker and use of toclizumab in Covid 19 pts.
-Portable CXR recommended to decrease chance of transmission and CT Scan used when CXR are not clear.
-In mild infection; continue or discontinue immunosuppressive medication, in this case, anti proliferative agent stopped initially while monitoring graft function, In sever cases CNIs are either decreased or stopped. Steroids are maintained and tx is always individualized.
-The efficacy of convalscent plasma in Covid pt is not clear.
-In non transplant pts, Remedesevir has shown quick recovery in covid pts,we need more studies before it can be applied broadly including in transplant popn
What is the level of evidence provided by this article?
-LEVEL IV – Case Series.
What is meant by the impact factor of a journal?
This is the average number of tomes that an article has been cited in its particular field/speciality over a 2 yr span of time.
I appreciate your well-structured summary in great details, and conclusions. I make note of the level of evidence that you have allocated to this article on COVID19 virus in renal transplant.
Thank you Prof.
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
1. Please summarise this article.2. What is the level of evidence provided by this article?3. What is meant by the impact factor of a journal?
Please summarise this article:
Introduction:
COVID-19 has close genomic structural similarities to SARS-CoV and MERS-CoV and has caused 203,818 reported deaths worldwide. 8 cases of kidney transplant recipients infected with COVID-19 due to long-term immunosuppression and comorbidities have been reported.
Case Reports
Patient 1
Had a deceased donor kidney transplant in December 2019 and presented with a high fever and no respiratory symptoms.
A nasal and throat swab for COVID-19 tested positive and she was on prednisone, tacrolimus, and mycophe-nolate mofetil.
Patient 2
A 71-year-old male with hypertensive nephropathy had a history of colon adenocarcinoma and was on immunosuppressive medications, but was tested positive for COV-ID-19.
Patients 3, 4, and 5 received live donor kidney transplants in February 2020, February 2019, and December 2019 respectively.
Patient 3 was test-ed positive for SARS-CoV-2 RNA despite unremarkable clinical examination, and his immunosuppressive drugs were prednisolone 5 mg OD, tacrolimus (trough level was 13.4 ng/mL), and MMF 500mg BD.
He was advised to drink plenty of fluids and report to the unit any new symptoms.
Patient 4 was a 63-year-old male with a history of IgA nephropathy with a deceased donor kidney transplant in December 2005.
He was admitted and received IV broad-spectrum antibiotics and paracetamol.
Patient 6:
A 71-year-old female with type II diabetes received de-ceased donor kidney transplantation in November 2015.
Her kidney functions deteriorated and continuous veno-venous hae-modiafiltration (CVVH) was commenced.
On April 2, she presented with fever (38.5°C) and no other complaint. Chest X-ray showed bilateral peripheral mid and lower zone consolidation.
Nasal and throat swabs were positive for COVID-19 RNA. Kidney function tests showed no change from baseline, and microbiological tests were negative.
She was admitted to the medical ward for adequate hydration and symptomatic treat-ment.
Patient 5 received a deceased donor kidney transplant in December 2019 and presented on April 6 with dry cough and shortness of breath.
Chest X-ray showed bilateral middle and lower zone consolidation, and SARS-CoV-2 RNA was positive.
Kidney function tests showed AKI, mild proteinuria, and leu-kocytosis. Microbiology workup showed positive urine culture for E.coli and negative blood culture.
Patient 6 was a 71-year-old female with type II diabetes who received a deceased donor kidney transplantation in November 2015.
On admission, her serum CRP was 344 mg/L and ferritin 2684 μg/L, with leu-kocytosis, lymphopenia, and interleukin-6.
Bronchoalveolar lavage showed moderate growth of aspergillus, and she received broad-spec-trum antibiotics and antifungals. Her kidney functions deteriorated, and continuous veno-venous hae-modiafiltration (CVVH) was commenced.
After 14 days, she was weaned off mechanical ventilation and transferred from the ITU to the medical ward.
Kidney function tests showed no change from baseline, and microbiological tests were negative.
Patient 4 was a 63-year-old male with a history of IgA nephropathy with a deceased donor kidney transplant in December 2005.
His immunosuppressive drugs were prednisolone 5 mg OD, tacrolimus (trough level was 13.4 ng/mL), and MMF 500mg BD. He presented on March 20 with fever and acute kidney in-jury (AKI).
Chest X-ray showed patchy bilateral consolidation, and SARS-CoV-2 RNA was positive.
He was admitted and received IV broad-spectrum antibiotics and paracetamol.
Kidney function tests improved (serum Cr de-creased to 113 μmol/L). He recovered and discharged home after 7 days.
Patient 6 was a 71-year-old female with type II diabetes who received de-ceased donor kidney transplantation in November 2015.
On April 2, she presented with fever (38.5°C) and no other complaint.
Chest X-ray showed bilateral peripheral mid and lower zone consolidation.
Kidney function tests showed no change from baseline, and microbiological tests were negative.
MMF was discontinued and discharged after 4 days with full recovery.
Discussion
This report presents 8 cases of COVID-19 infection in kidney transplant patients from Sheffield Kidney Institute, UK.
The median age of the patients was 48.5 years and the most common initial symptoms were fever (5 patients) and cough (5 patients).
All 8 patients were receiving prednisone and tacrolimus, 7 patients were receiving mycophenolate mofetil, and 1 patient was receiving azathioprine.
Blood results showed that all patients had lymphopenia and high CRP.
A portable chest X-ray was performed in 7 patients, which was clear in 2 of them, and the rest had a picture consistent with viral pneumonia.
One patient required ITU admission, one patient required mechanical ventilation, and one patient required ward-based oxygen therapy.
Antiproliferative immunosuppressive drugs were discontinued for all patients due to multiple risk factors, including immunosuppression, underlying CKD, and associated comorbidities.
Lianget al. [11] reported that 1% of COVID-19 patients had a history of malignancy, which was higher than the preva-lence of cancer in the overall Chinese population (0.29%).
The most frequent tumour was lung cancer, and the most frequent presentation was fever (5 patients) and cough (5 patients).
Two large studies demonstrated that 82-87% of their patients had a fever, while patients with cough ranged from 44 to 65.
Two of our patients had AKI, and the pathophysiology of renal involvement is still unclear, but theories suggest a cytokine storm syndrome or direct renal injury by the virus.
Scientists succeeded in isolating SARS-CoV-2 from a urine sample of an infected patient.
COVID-19 infection is associated with high CRP and lymphopenia, which can lead to adverse outcomes such as ARDS development, myocardial damage, and death.
Continuous renal replacement therapy may play a role in the management of AKI in COVID-19 patients.
Serum ferritin is an acute-phase protein, but its sensitivity and specificity are unknown.
IL-6 is considered a novel biomarker for COVID-19 diagnosis, but it is not routinely measured and there is no clear evidence to support the role of IL-6 blocker (tocilizumab) in treatment.
Chest X-ray was used as a first-line triage tool, but CT decontamination may disrupt service availability and portable chest X-ray should be considered to reduce transmission.
CT is not recommended unless there is high suspicion of CXR in a seriously ill patient, and it is important to be familiar with the radiological findings of COVID-19 on chest X-ray.
When managing immunosuppression in kidney transplant recipients, the age, severity of infection, post-trans-plant duration, any other associated comorbidity, tissue mismatch, and any episodes of rejection should be considered.
The treatment should be individualized based on the careful assessment of each patient.
The US Food and Drug Administration has authorized the use of remdesivir as a treatment option for hospitalized COVID-19 patients.
Conclusion
The presentations of COVID-19-infected renal transplant patients were similar to the general population, with fever and cough being the most frequent symptoms.
Supportive treatment could be sufficient, and short hospital stay with self-isolation on discharge reduces the burden on the health service and protects the public.
Treatment with remdesivir should be done in a hospital setting with CNI drug level monitoring.
What is the level of evidence provided by this article?
The level evidence is IV
What is meant by the impact factor of a journal?
The impact factor (IF) is a measure that reflects the average number of citations to articles published in journals, books, thesis, project reports, newspapers, conference/seminar proceedings, documents published in internet, notes, and any other approved documents.
It is used to evaluate the relative importance of a journal within its field and to measure the frequency with which the “average article” in a journal has been cited in a particular time period.
Journals with higher IFs are believed to be more important than those with lower ones. Journal which publishes more review articles will get maximum IFs.
Impact factor (IF) is the average number of citations received per article published in a journal during the 2 preceding years.
It is calculated each year by Thomson scientific for those journals that it indexes, and is published in Journal Citation Reports .
For example, if a journal has an IF of 3 in 2008, then its papers published in 2006 and 2007 received three citations each on average in 2008.
The IF of any journal may be calculated by the formula;2012 impactfactor =A/BWhere A is the number of times articles published in 2010 and 2011 were cited by indexed journals during 2012.
In an ideal world, evaluators would read each article and make personal judgments.
I make note of of your suggestion ‘In an ideal world, evaluators would read each article and make personal judgments.’ But is it really possible without AI to go through almost 6000 medical journals every month.
I agree with your implied message as I would understand: ‘henceforth, we rely on every else each with specific interest in their respective articles and calculate mathematically to express popularity of journals’.
I like your well-structured summary in great details, and conclusions. I appreciate level of evidence that you have allocated to this article on COVID19 virus in renal transplant.
Introduction:
The novel COVID-19 infection, which arose in Wuhan, China, in December 2019, shares genomic structural similarities with the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused the 2003 SARS pandemic and the 2012 MERS pandemic. COVID-19 infected 210 nations and killed 203,818 persons till April 26, 2020.
30,000 UK deaths have occurred.
it is believed that kidney transplant recipients have a high infection risk due to long-term immunosuppression and comorbidities. COVID-19 in renal transplant recipients is poorly studied.
so, this is a case reports of 8 cases of COVID-19 in post kidney transplant.
Patient 1: a 21-year-old female with a deceased donor kidney transplant in December 2019 arrived on March 30 with fever (39.2°C). No respiratory symptoms, she felt lethargic and ill. Except a high temperature, the chest X-ray and clinical examination were normal.
Negative blood and urine cultures. Positive COVID-19 nose and throat swabs. was on CCB and β-blockers for hypertension, prednisone 5 mg od, tacrolimus 2 mg twice a day, and mycophenolate mofetil 250 mg (BD). stopped MMF & Intravenous fluids &supportive measures. Discharged after 2 days with stable RFTs.
Patient 2: 71-year-old male with hypertensive nephropathy who had a kidney graft in February 2016. June 2019 colon adenocarcinoma history. Baseline Cr was 240–260 μmol/L. presented with respiratory symptoms & spotty bilateral consolidation. He was admitted after a positive COVID-19 swab. MMF stopped and had IV hydration and symptomatic therapy. He left two days later with stable kidney functions.
Patient 3: also responded to holding MMF & supportive management with self-isolation at home.
Patient 4: 63-year-old male with IgA nephropathy and a deceased donor kidney transplant in December 2005. Calcium channel blockers control his hypertension. presented with a fever (38.8°C) and AKI; Cr 297 μmol/L, baseline 110). SARS-CoV-2 RNA was positive, and the chest X-ray exhibited patchy bilateral consolidation. Blood culture showed staphylococcus aureus. CRP was 175 mg/L and ferritin 929 μg/L. Prednisolone 5 mg OD, tacrolimus (2.7 ng/mL), and MMF 500 mg BD were his immunosuppressive drugs. The patient was hospitalised for IV broad-spectrum antibiotics and paracetamol. stopped MMF and increased tacrolimus. Kidney function improved (serum Cr dropped to 113 μmol/L). After 7 days, the patient was home.
Patient 5: A 47-year-old bronchial asthmatic woman received a deceased donor kidney transplant in December 2019. came with respiratory symptoms& x-ray findings.
COVID-19-positive. AKI and moderate proteinuria. E. coli was found in urine but not blood. On admission, serum CRP was 344 mg/L and ferritin 2684 μg/L, with leucocytosis (white cell count 25.8 × 109/L) and lymphopenia (lymphocyte count 0.7 × 109/L). Interleukin-6 was 22.2 pg/mL. She was admitted to ICU for non-invasive ventilation (CPAP for type 1 respiratory failure). needed intubation and invasive ventilation. Aspergillus moderated in bronchoalveolar lavage. got broad-spectrum antibiotics and antifungals. No antivirals were administered. MMF stopped. She got anuric and needed CVVH. She was transferred from the ICU to the medical ward after 14 days of mechanical ventilation. Her renal functions improved and CVVH stopped. She left 7 days later.
The other 3 patients also responded to supportive measures plus holding antiproliferative drugs.
Discussion:
This paper describes 8 COVID-19 infections in kidney transplant patients. Four males and four females were 48.5 years old (range from 21 to 71 years). Three patients underwent kidney transplants within three months, and the remainder were transplanted over a year ago. Fever and cough were the most common early symptoms (5 cases) (5 patients). 8 individuals received prednisone and tacrolimus, 7 received mycophenolate mofetil, and 1 received azathioprine. Cases 4 and 5 had AKI, and one needed CVVH (case 5).
Patients experienced lymphopenia and elevated CRP. Three individuals had elevated ferritin, and one had high interleukin-6. Two of seven patients had clear chest X-rays, while the rest had viral pneumonia.
One was outpatient and recommended to self-isolate at home, while the other 7 were hospitalized. One Icu patient needed mechanical ventilation (case 5). She is being treated for aspergillosis after bronchoalveolar lavage (another contributing factor for deterioration). Case 8 needed ward-based oxygen. The remaining 6 patients got supportive care on the renal ward (intravenous fluid therapy, monitoring renal function, and symptomatic treatment with or without ward-based oxygen therapy based on oxygen saturation). All patients stopped antiproliferative drugs.
Immunosuppression, CKD, and comorbidities such hypertension and diabetes put transplant patients at risk of infection.
Fever and cough were the most common symptoms in our case series (5 patients). Cough followed fever as the most prevalent symptoms.
AKI was rare (3–9%) in COVID-19-infected patients. Recent studies found more renal affection. Cheng et al. found 44% proteinuria, 26.7% haematuria, and 14.1% elevated serum Cr in 710 individuals. Cytokine storm syndrome or virus-induced renal damage may explain renal involvement. SARS-CoV-2 was isolated from a patient’s urine, suggesting it targets the kidney.
Continuous renal replacement therapy improved SARS and MERS-related AKI. High-volume hemofiltration was thought to remove inflammatory cytokines (TNF, IL-6, and IL-1β) that cause kidney damage. Hence, continuous renal replacement treatment may treat COVID-19 AKI.
All patients had lymphopenia and elevated CRP. Guan et al. found lymphopenia in 83.2% of infected patients on admission. Another study linked lymphopenia to ARDS.
Several studies linked COVID-19 to elevated CRP. Guan et al. [5] found that 60.7% of patients had raised CRP, with severe cases having a higher CRP (81.5 vs. 56.4%). High CRP has been linked to adverse outcomes like ARDS, myocardial injury, and mortality. Several studies linked increased serum ferritin to ARDS and death. The outcome sensitivity and specificity of ferritin, an acute-phase protein, remain unknown.
Novel COVID-19 biomarker IL-6. Case 5 was high. Chen et al. [20] found 52% (51/99) of patients had elevated IL-6 on admission. Several investigations linked higher IL-6 levels to higher mortality.
7 individuals had chest X-rays. Five exhibited bilateral patchy consolidation, and two had no COVID-19 symptoms. CT findings dominated COVID-19 radiological findings. This approach burdened radiology departments and made radiology suite infection management difficult, hence the American College of Radiology recommends portable chest X-ray to minimize infection.
Because COVID-19 testing takes time, Italian and British hospitals use chest X-rays for triage. The British Society of Thoracic Imaging (BSTI) recommends CT only for high suspicion with normal or unclear CXR in very sick patients.
6 patients stopped their antiproliferative medicines and underwent supportive treatment; 1 needed oxygen therapy, and 1 needed mechanical ventilation. No patients received particular antiviral medications. Kidney transplant recipients should consider age, infection severity, post-transplant length, comorbidities, tissue mismatch, and rejection episodes.
With minor infections, immunosuppressive medications are usually continued or reduced. Despite the study’s limited sample size, we recommend discontinuing azathioprine and mycophenolate mofetil and closely monitoring patients.
In severe infections, stop antiproliferative medications first, especially in the absence of UK guidelines and the unpredictable course of COVID-19 infection in this population. Calcineurin inhibitors can be stopped while corticosteroids are continued in severe patients requiring mechanical ventilation. Personalized treatment based on patient assessment is essential.
Convalescent plasma was utilized to treat SARS patients. A meta-analysis found that many trials had small sample sizes and no control groups, casting doubt on its usefulness.
Chu and colleagues found no benefit with lopinavir and ritonavir in SARS-CoV patients. Additional studies showed that remdesivir, a broad-spectrum antiviral nucleotide prodrug, can treat MERS-CoV and SARSCoV. the FDA has approved remdesivir for hospitalized COVID-19 patients.
Conclusion:
fever and cough were the most frequent symptoms.
supportive treatment could be sufficient or at least to be tried first.
recommend treatment with remdisivir in a hospital setting where CNI drug level monitoring is available.
Level of evidence:
Level 4, case series
Impact factor of a journal:
used to measure the frequency with which the “average article” in a journal has been cited in a particular time period, which in turn reflect the potency & importance of the journal.
calculated based on a two-year period via dividing the number of citations by the number of citable articles.
I like your well-structured summary in great details, and conclusions. I appreciate level of evidence that you have allocated to this article on COVID19 virus in renal transplant.
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
Case Reports
Patient 1
Scenario
· 21-year-old hypertensive female had a DD kidney transplant in December 2019.
· Presented around 3 months post- transplant with fever 39.2°C, lethargic and generally unwell.
· No respiratory symptoms and Clinical examination was unremarkable.
· Chest X-ray was clear, urine and blood cultures were negative.
· A nasal and throat swab for COVID-19 tested positive.
· She was on prednisone, tacrolimus and MMF 250 mg.
Management:
· Admitted and received supportive medical treatment.
· MMF was discontinued
Outcome:
· Discharged after 2 days with full recovery and stable kidney functions.
Patient 2:
Scenario
· 71-year-old hypertensive male received a kidney graft in February 2016.
· History of colon adenocarcinoma in June 2019.
· His baseline Cr was 240–260 μmol/L.
· IS regimen included prednisolone 5 mg OD, tacrolimus (trough level was 6.4 ng/mL), and MMF 250 mg BD.
· Presented with a dry cough, no other symptoms and stable vital signs.
· Chest X-ray: patchy bilateral consolidation.
· positive for COVID-19
Management
· Admitted to hospital.
· MMF discontinued and received supportive treatment.
Outcome
· Discharged 2 days later with stable kidney functions.
Patient 3:
Scenario
· 50-year-old male received a live donor kidney transplant in February 2020.
· IS drugs were prednisolone 5 mg OD, tacrolimus (trough level was 13.4 ng/mL), and MMF 500 mg BD
· Presented 2 months after transplantation with productive cough.
· Chest X-ray was clear
· Tested positive for SARS-CoV-2 RNA.
· Kidney function tests were stable.
Management
· Discontinuation of MMF, reduction of tacrolimus dose.
· Self-isolation at home.
Patient 4:
Scenario
· 63-year-old hypertensive male, DD kidney transplant in December 2005.
· Presented on March 20 with fever (38.8°C) and AKI; Cr 297 μmol/L, baseline 110 μmol/L).
· The chest X-ray showed patchy bilateral consolidation.
· SARS-CoV-2 RNA was positive.
· IS regimen was prednisolone 5 mg OD, tacrolimus (trough level was 2.7 ng/mL), and MMF 500 mg BD.
Management
· Admission and received IV broad-spectrum antibiotics and paracetamol.
· Stopped MMF and increased the tacrolimus dose.
Outcome
· Kidney function tests improved
· The patient recovered and discharged home after 7 days.
Patient 5:
Scenario
· 47-year-old female with bronchial asthma received a DD kidney transplant in December 2019.
· She was maintained on prednisolone 5 mg OD, tacrolimus with levels between 5 and 7 ng/mL, and MMF 250 mg BD.
· She presented with dry cough and shortness of breath but no fever.
· Chest X-ray: bilateral middle and lower zone consolidation.
· COVID-19 test positive.
· AKI (Cr 302 μmol/L and baseline 162 μmol/L), and mild proteinuria (urine protein/Cr ratio 127 mg/ mmol and baseline <30 mg/mmol).
· Microbiology workup showed positive urine culture for E. coli and negative blood culture.
· She was tachypnoeic with a respiratory rate of 36 breaths/min, and the peripheral oxygen saturation was 80%
Management
· Admitted to the ITU) for CPAP
· Her respiratory functions got worse and she required invasive ventilation.
· Bronchoalveolar lavage showed moderate growth of aspergillus.
· She received broad-spectrum antibiotics and antifungals.
· MMF was discontinued.
· Her kidney functions deteriorated, and received CVVH.
Outcome
· After 14 days, she was weaned off mechanical ventilation.
· Her kidney functions improved (estimated glomerular filtration rate was 17 mL/min per 1.73 m2, urine protein/Cr ratio, 40 mg/mmol).
· She was discharged 7 days later.
Patient 6:
Scenario
· A 71-year-old female with type II diabetes, DD kidney transplantation in November 2015.
· IS therapy included prednisolone, tacrolimus, and MMF.
· Presented with fever (38.5°C) and no other complaint.
· Chest X-ray showed bilateral peripheral mid and lower zone consolidation.
· Swabs were positive for COVID-19 RNA.
· Kidney function tests showed no change from baseline, and microbiological tests were negative.
Management
· Admitted to the medical ward for adequate hydration and symptomatic treatment.
· MMF was discontinued.
Outcome
· Discharged after 4 days with full recovery.
Patient 7:
Scenario
· 40-year-old hypertensive female received DD kidney transplantation in June 2017.
· Maintained on prednisolone, tacrolimus, and MMF.
· she presented with fever (39°C) and dry cough with no other symptoms
· Swabs for COVID-19 RNA were positive.
· Kidney function tests were stable and microbiological analyses were negative.
Management
· Admitted to the medical ward.
· MMF was discontinued, Paracetamol and IV fluids were administered.
Outcome
· Discharged after 4 days with full recovery.
Patient 8:
Scenario
· 38-year-old male with a failing kidney transplant.
· Presented with productive cough and shortness of breath for 2 days.
· Maintained on prednisolone 5 mg OD, tacrolimus, and azathioprine.
· He had tachypnoea and oxygen saturation of 89% on room air, which improved on oxygen through a nasal cannula.
· Swabs were positive for COVID-19 RNA.
· Kidney function tests remained unchanged despite the high baseline Cr.
· Chest X-ray; bilateral infiltrates.
Management
· Discontinuation of azathioprine, reduction of tacrolimus dose, and increase of prednisolone dose to 15 mg OD.
Outcome
· He did not require any dialysis.
· Oxygen saturation recovered
· The patient was discharged after 2 days.
Discussion
· In this report, 8 cases of COVID-19 infection in kidney transplant patients were reported from Sheffield Kidney Institute, UK.
· The most common initial symptoms were fever and cough.
· All patients were receiving prednisone and tacrolimus, 7 patients were receiving mycophenolate.
· Two patients had AKI 1 of them required CVVH.
· CCVH showed promising results in AKI associated with SARS and MERS. It could remove inflammatory cytokines involved in the pathogenesis of renal injury.
· All patients had lymphopenia and high CRP.
· CXR in most of them had a picture consistent with viral pneumonia.
· One was managed as an outpatient and one patient required ITU admission. Aspergillosis was confirmed in the latter.
· Transplant patients are at a high risk of COVID 19 due to multiple risk factors, including immunosuppression, underlying CKD, and associated comorbidities, especially hypertension and diabetes.
· Five out of seven patients had bilateral patchy consolidation in CXR. Which suggest viral infection, the recommendation is to use portable chest X-ray to reduce the transmission of infection rather than CT chest.
· Regarding IS, in 6 of these patients, antiproliferative drugs were stopped. They recommended the treatment should be individualized based on the careful assessment of each patient.
· In this series, none of the patients received specific antiviral drugs.
· In some studies, remdesivir showed promising results. Based this results, the FDA has authorized the use of remdesivir as a treatment option for hospitalized COVID-19 patients with close monitoring of CNI level.
Conclusion
· Based on this experience, supportive treatment could be sufficient.
· Clinical examination supported by oxygen saturation and portable CXR rather than CT scan could be enough and limit the spread of infection.
· Short hospital stay with self-isolation on discharge reduces the burden on the health service and protect the staff and the public.
Level of evidence: 4 case series
Impact factor of a journal
· Is a scientometric index that reflects the yearly mean number of citation of articles published in the last two years in a given journal provided by Clarivate web of science.
· Clarivate web of science provides researchers faculty and students with quick, powerful access to the word leading citation database.
I like your well-structured summary in great details, and conclusions. I appreciate level of evidence that you have allocated to this article on COVID19 virus in renal transplant.
Please summarise this article.
Introduction;
–The new coronavirus disease 2019 (COVID-19) infection emerged in Wuhan city, China, in December 2019.
-By April 26, 2020, infections related to coronavirus disease 2019 (COVID-19) affected people from 210 countries and caused 203,818 reported deaths worldwide.
-Among kidney transplant recipients, they have a high risk of infection due to long-term immunosuppression and associated comorbidities.
-There are few studies discussed the outcome of COVID-19 in kidney transplant recipients.
Aim;
-Pretending experience in managing COVID-19 disease in renal transplant patients in the absence of strong evidence.
Methodology;
-They report 8 cases of kidney transplant recipients infected with COVID-19 (median age = 48.5 years; range = 21–71 years), including 4 males and 4 females. The most frequently associated comorbidity was hypertension.
-The most common presenting features were fever and cough & the main radiological investigation was a portable chest X-ray.
-Other common features included lymphopenia, high C-reactive protein, and a very high ferritin level.
-Overall, 1 patient was managed as an outpatient, the remaining 7 required hospital admission, 1 of those admitted patients referred to the intensive therapy unit.
-Management included supportive treatment (intravenous fluid therapy, monitoring renal function, and symptomatic treatment with or without ward-based oxygen therapy depending on oxygen saturation) and discontinuation of the antiproliferative immunosuppressive drugs.
-Seven patients recovered and discharged home to self-isolate & one patient required intensive care treatment and mechanical ventilation.
-Supportive treatment could be sufficient for the management or to be tried first.
-They also found that short hospital stay with self-isolation on discharge reduces the burden on the health service and protect the staff and the public.
Conclusion;
-The presentations of COVID-19 infected renal transplant patients were not different from the general population where fever and cough were the most frequent symptoms.
-Covid-19 infection in transplant patients did not behave differently from the general population, Because of the small sample size, we could not evaluate the effect of immunosuppression on the course of the disease, but at least it is not a detrimental effect.
-Based on our experience, supportive treatment could be sufficient or at least to be tried first. It is worth mentioning that the clinical examination supported by simple bedside measures such as oxygen saturation and portable CXR rather than CT scan could be enough and limit the spread of infection.
-Since remdisivir was approved for the treatment of COVID-19 and its interaction with CNI is yet unknown, we recommend treatment with remdisivir in a hospital setting where CNI drug level monitoring is available.
What is the level of evidence provided by this article?
-This article is Case Series and a Brief Review of Current Evidence with (LOE IV)What is meant by the impact factor of a journal?
–Impact factor (I. F.) is commonly used to evaluate the relative importance of a journal within its field and to measure the frequency with which the “average article” in a journal has been cited in a particular time period.
-Journal which publishes more review articles will get highest IFs.
-The impact factor of a journal is calculated by dividing the number of current year citations to the source items published in that journal during the previous two years .
I like your well-structured detailed summary, and conclusions. I appreciate level of evidence that you have allocated to this article on COVID19 virus in renal transplant.
Summary
This report summarizes the clinical presentation, management, and outcome of 8 cases of post-kidney transplant covid 19 infections from a single center in the UK
Published in nephron with an Impact score of 3.26 for the year 2022/2023
we can see covid 19 pneumonia occurs between 1-6 months after transplantation with variable and nonspecific symptoms but fever and cough are the predominant clinical features with or without AKI, patient characteristics, and demography are summarized in table 1 and table 2 summarize the labs and CT images while tabe3 summarizes the treatment and outcome.
the average age at the time of infection was 48 years (younger, 4 males and 4 females with predominate clinical presentation of fever, and cough, two patients had AKI and only one required CVVH as a mode of RRT .nonspecific cx r finding from normal Typical viral infiltration, All patients at tacrolimus based IS with prednisolone and 7 patients were on MMF and the only case was on azathioprine
the most frequent presentation in this case series fever with cough, two cases have AKI and in one case was severe AKI that mandates initiation of CRRT in icu
the comorbid disease was found in 6 patients including HTN IN 4, TYPE 11 DM in one, and malignancy in one case while bronchial asthma with superadded aspergillosis in one case, most of the patients required hospital admission and received supportive care with IVF and other supportive care one case treated as OPD with self-isolation
MMF was kept on hold in all cases and continued on tacrolimus with steroids
All patients have lymphopenia with high CRP and high ferritin was found in 3 cases in this case series they don’t use IL 6 routine monitoring however most of the r
reports found a significant link between severe covid 19 infections in those with lymphopenia, high CRP, and high ferritin associated with ARDS and increased mortality rate, especially with high 1L6 level (a novel marker for the diagnosis of covid 19)
renal involvement in covid 19 infection was reported in many studies and it varies from AKI to glomerulonephritis (proteinuria, hematuria) , TMA
in this series, only two cases had AKI one recovered with hydration and supportive therapy, and one case of severe covid 19 on the background of ASTHMA and get superadded aspergillosis this patient had oliguric AKI requiring high convection CVVH
In conclusion, covid 19 severity and outcome are similar to the general population, and supportive therapy with hydration and withholding the antimetabolites was found to be effective in managing covid 19 in post-kidney transplantation, use of antivirals like remdesivir- had 31% faster time to recovery in severe covid 19 compared to the placebo group in one study, while the convalescent plasma benefit was questionable, also the use of clinical assessment with o2 saturation, and portable CXR should be the first line work up that limit the covid19 transfer and better infection control, limit the use of conventional CT case by case
Limitation
Case series from a single center
What is the level of evidence provided by this article?
Level 4, case series
What is meant by the impact factor of a journal?
It’s used to assess the frequency of citations over 2 years, the Impact factor of nephron 2.6 for 2021-2022
I like your well-structured detailed summary. I appreciate level of evidence that you have allocated to this article on COVID19 virus in renal transplant.
Hi Dr Saja,
I appreciate your listing of limitations of this article. Please use sub-headings, under the heading of ‘Summary’ to make easier to read your write-up. Please use bold or underline to highlight headings and sub-headings.
Please do not leave a gap between a full stop (or comma) and a preceding word, otherwise a new line may start for a full stop (or comma). I quote from your write-up, ” .nonspecific cx r finding from normal Typical viral infiltration, All.”
Thank you Prof for the feedback noted .
So nice of you to take note of my suggestions, Dr Saja.
Please summarise this article
Introduction
Covid 19 has genomic similarities to SARS-CoV and MERS-CoV.
Kidney transplant recipients are thought to have high risk of infections due to the use of immunosuppressive therapy and associated co-morbidities.
Cases
8 reported cases;
Discussion.
Hypertensive and diabetic patients have a double risk of Covid 19 while COPD patients have a four fold risk.
Pathophysiology of renal injury is unclear with postulated theories of cytokine storm and direct virus injury to the kidney.
Continuous renal replacement therapy may play a role in management of AKI in Covid 19 by removal of the inflammatory cytokines.
Lymphopenia, high CRP and ferritin levels have been associated with ARDS and unfavourable outcomes.
Patients with mild infections can continue or reduce immunosuppression.
Severe infections stop anti-proliferative first.
Severe cases requiring mechanical ventilation can stop CNI and continue on steroids.
Conclusions
Covid 19 infections in the transplant population presents similar to general population.
Supportive treatment could be sufficient and should be tried first.
Short hospital stay with self isolation reduce the burden on health care.
What is the level of evidence provided by the article?
This is a case series report hence level IV.
What is meant by impact factor of a journal?
It is used as an indicator of the importance of a journal in its field where journal with high impact factors are considered more important.
It measures the frequency a journal has been cited in a particular period which is usually 2 years.
Usually the journal must have completed minimum 3 years after publication hence can’t be done in new journals.
I like your well-structured detailed summary. I appreciate level of evidence that you have allocated to this article on COVID19 virus in renal transplant.
Observations
Therapy received
Conclusion and recommendations
Case series, level of evidance IV
I like your well-structured detailed summary. I appreciate level of evidence that you have allocated to this article on COVID19 virus in renal transplant.
SUMMARY
Introduction
The epidemic of COVID-19 which started in Wuhan City, China has already spread to over 200 countries by April 2020, with a mortality of over 200 thousand as of that time.
The long-term immunosuppressive state and the background comorbidity among CKD patients made most transplant physicians conclude that kidney transplant patients are at great risk of COVID-19 infection
This article presents a case series with the data of the participants as follows
Demography, clinical data, and findings
Conclusion
The study concluded that, the clinical presentation of post-transplant patients with COVID-19 infection is not different from the general population and that those with mild symptoms can be managed at home by self-isolation, and medication adjustment, and this will reduce the burden of the strained medical facility and the personnel.
The level of evidence is 4
The impact factor is used to evaluate the importance of a journal within its field and to measure the rate at which an article in the journal is been cited.
It is usually calculated by the ratio between the number of citations received in that year for publications in that journal that were published in the two preceding years and the total number of “citable items” published in that journal during the two preceding years
For example the impact factor of a journal in 2021
IF = Citation in the years 2021
Publication in the year 2021 + Publication in the year 2019
Hi Dr Abiola,
I am afraid, I would not agree with your answer.
Correct answer of IF for 2021 is:
A = the number of times articles published in 2019 and 2020 were cited by indexed journals during 2021.
B = the total number of “citable items” published in 2019 and 2020.
A/B = 2021 impact factor
1.Please summarise this article.Outcomes of COVID-19 infection in renal transplant; evidence from case reports
Muhammed Ahmed ELhadedy et .al reported 8 cases of COVID-19 In transplant recipients at Sheffield Kidney institute.
Conclusion
2.What is the level of evidence provided by this article?
3.What is meant by the impact factor of a journal?
I like your reply about IF. What are limitations or flaws of IF?
Thank you prof, yes
Introduction:
The new coronavirus disease 2019 (COVID-19) infection emerged in December 2019, resulting in a high mortality rate worldwide. However, the data on its effect on kidney transplant recipients are limited.
This study addressed the experience of COVID-19 infection in 8 KTRs (4 female and 4 male).
Case 1:
A young KTR , presented 3 months post-Tx mainly with fever and lethargy and no respiratory symptoms. Normal CXR and COVID-19 swab was positive. She had hypertension on treatment..
Case 2:
An old male KTR for hypertensive nephropathy (2016), his course complicated with colon cancer. He presented only with dry cough, CXR showed bilateral patchy infiltrate and his tested positive for COVID-19.
Case 3:
KRT for DM transplanted 2015, presented with fever only and abnormal CXR
Case 4:
KTR, transplanted in 2017, presented with fever and dry cough only. She was tested positive for covid.
All above mentioned cases were treated with supportive measures and discontinuation of MMF. They had a full recovery and were discharged in few days with stable kidney function.
Case 5:
KTR presented 2 months post-Tx (Wagner granulomatosis) with productive cough only, CXR; clear and tested positive for COVID. He was managed with stopping MMF and home isolated.
Case 6:
KTR transplanted in 2005 for IgAN. He presented with fever and AKI. His CXR showed bilateral infiltrate, high inflammatory markers, tested positive for covid and he has staph. aureus sepsis. He was managed supportively with broad spectrum antibiotic, stopping MMF and was discharged after 7 days with improvement in graft function.
Case 7:
Female with bronchial asthma, presented 4 months post KT with dry cough, respiratory distress and AKI. She rewuired ICU admission for respiratory support (initially CPAP then MV). MMF was discontinues. She was treated with broad spectrum antibiotic and antifungal ( UIT, aspergillus BAL ). She required CVVH for sever AKI. The support (MV and CVVH) weaned later on and discharge after 7 days from ICU transfer with low GFR.
Case 8:
KTR (2013) presented with productive cough and SOB. She required O2 for hypoxia, abnormal CXR. She was managed with stopping azathioprine and reducing Tacrolimus dose while increasing prednisolone dose. She did not require dialysis and weaned off O2.
Conclusion:
-The most common initial symptoms were fever and cough
-All patients had lymphopenia and high CRP, ferritin.
-CXR variable from clear, to picture of viral pneumonia.
-The management included supportive care and discontinuation of antiproliferative drugs.
-IL-6 is considered a novel biomarker for COVID-19 diagnosis associated with an increased risk of mortality.
-There is no clear evidence to support the role of IL-6 blocker (tocilizumab) in treatment of COVID-19 in both transplant and non-transplant population.
– Portable chest X-ray was considered to reduce the transmission of infection
– Generally, in mild infections, the usual practice is to continue or reduce the dose of immunosuppressive drugs. Suggestion to discontinuation of the antiproliferative drugs while monitoring the patients closely.
– As there is no clear guideline the treatment should be individualized based on the careful assessment of each patient.
– Remdesivir provided faster time to recovery and approved by FDA as treatment option.
Level of evidence: level 4 case series
Impact factor of a journal:
It is a measure of the frequency of the average article in a journal has been cited in a particular year. It is used to measure the importance or rank of a journal by calculating the times its articles are cited.
The calculation is based on a two-year period and involves dividing the number of times articles were cited by the number of articles that are citable.
I like your summary, analysis and take home messages.
Moreover, I do agree with your level of evidence that you have assigned to this article: IV. ’.
1.Please summarize this article.
Introduction
Patients’ demographics & clinical characteristics
Tests & results on the day of admission
Management & outcome
Discussion
Conclusions
===========================
2.What is the level of evidence provided by this article?
Level V
===========================
3.What is meant by the impact factor of a journal?
Calculation of 2010 Impact Factor (IF):
A= the number of times articles published in 2008 & 2009 were cited by indexed journals during 2010.
B= the total number of citable items published in 2008 & 2009
A/B= 2010 impact factor.
References
I like your summary, analysis and take home messages.
However, I do NOT agree with your level of evidence that you have labelled it as level ‘V’.
Typing whole sentence in bold or typing in capitals amounts to shouting.
I. COVID-19 in Renal Transplant
Please summarise this article.
INTRODUCTION
coronavirus disease 2019 (COVID-19) affected people from 210 countries and caused 203,818 reported deaths worldwide this by April 26, 2020. In the UK, mortality cases exceeded 30,000 .
Due to long-term immunosuppression , kidney transplant recipients have a high risk of infections.
DISCUSSION
This report, presenting 8 cases of COVID-19 infection in kidney transplant patients from Sheffield Kidney Institute, UK. The median age of patients was 48.5 years , including 4 males and 4 females.
Three patients had kidney transplantation within the last 3 months, and the rest were transplanted for more than a year.
initial symptoms :
fever (5 patients)
cough (5 patients).
All 8 patients were receiving prednisone and tacrolimus.
7 patients were receiving mycophenolate mofetil.
1 patient was receiving azathioprine
Two patients had AKI .
1 of them required continuous veno-venous hemofiltration
One patient was managed as an outpatient , 7 patients requiring hospital admission one of them need ICU and mechanical ventilation, Bronchoalveolar lavage of this patient confirmed aspergillosis for which she is receiving antifungal treatment .
One patient required ward-based oxygen therapy.
The other 6 patients received supportive therapy on the renal ward.
Antiproliferative immunosuppressive drugs were discontinued for all patients.
Risk factors :
Immunosuppression.
Underlying CKD.
Associated comorbidities:
Hypertension and diabetes(douple risk)
Bronchial asthma and aspergillosis
COPD(5 fold risk)
Pathological pictures
Blood results :
All patients had lymphopenia and high CRP.
Proteinuria(44%)haematuria(26.7%), and had high serum Creatine(14.1%).
Three patients had elevated serum ferritin, and 1 patient had high serum interleukin-6 (IL-6).
A portable chest X-ray was performed in 7 patients, clear in 2 of them, and the rest had a picture consistent with viral pneumonia.
TRETMENT
Stop Antiproliferative drugs .
Oxygen therapy
Supportive management may required mechanical ventilation .
plasma – derived from the blood may needed in sever cases.
Lopinavir and ritonavir may used.
Remdesivir showed promising results.
Conclusion
The presentations of COVID-19 infected renal transplant patients were not different from the general population .
Fever and cough were the most frequent symptoms.
Transplant patients did not behave differently from the general population as far as COVID-19 infection is concerned.
Because of the small sample size, we could not evaluate the effect of immunosuppression on the course of the disease, but at least it is not a detrimental effect.
Supportive treatment could be sufficient or at least to be tried first.
Clinical examination supported by simple bedside measures such as oxygen saturation and portable CXR rather than CT scan could be enough and limit the spread of infection.
Short hospital stay with self-isolation on discharge reduces the burden on the health service and protect the staff and the public.
Since remdisivir was approved for the treatment of COVID-19 and its interaction with CNI is yet unknown, we recommend treatment with remdisivir in a hospital setting where CNI drug level monitoring is available.
What is the level of evidence provided by this article?
Level V.
What is meant by the impact factor of a journalecipients: Case Series and a Brief Review of Current Evidence
Is measure of the frequency where average articlein a journal had been cited in certain year. Journal which publishes more review articles will get highest IFs.
I like your summary, analysis and take home messages.
Hower, I do NOT agree with your level of evidence that you have labelled it as level ‘V’.
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence.
COVID-19 is emerged on 2019 in Wuhan city, China, there is a concept between clinician that kidney transplant recipients have a high risk of infection due to long-term immunosuppression and associated comorbidities.
Herein, this case series report 8 cases of kidney transplant recipients infected with COVID-19 from Sheffield Kidney Institute, UK.
The demographic characteristic showed that the median age of patients was 48.5 years, were 4 males and 4 females, three patients had recent KTX less than 1 year, and the rest were transplanted for more than a year. The most common initial symptoms were fever and cough (5 patients). All 8 patients were receiving prednisone and tacrolimus, 7 patients were receiving Mycophenolate mofetil, and 1 patient was receiving azathioprine. One of them required RRT(low incidence of AKI) and have a role remove inflammatory cytokines .One treated as outpatient and others need hospitalization.
Regarding laboratory investigations shown high CRP , ferritin, IL-6 and lymphopenia in most of cases and has negative impact on the cases, suggested that higher serum ferritin is associated with ARDS development, also IL-6 levels can be associated with an increased risk of mortality and death.
Most of them recovered with only supportive treatment and discontinuation of the antiproliferative immunosuppressive drugs, only 1 patient needed oxygen therapy, and 1 required mechanical ventilation, but we should deal a case by case management, for example if our patient worsening we should be cautious to stop CNI and increasing steroid therapy with close monitoring of graft to avoid attack of rejection.
Conclusion:
Post KTX recipient is on high risk for COVID-19 infection due to multiple co-morbidities and immunosuppreive status but we should treat every case according to its clinical state, isolation is important and discontinuation of the antiproliferative immunosuppressive drug is the quintessential of the management plan with supportive treatment.
Level of evidence :Case series (IV).
What is meant by the impact factor of a journal?
Impact factor (IF) is the average number of citations received per article published in a journal during the 2 preceding years which measures the importance or rank of the journal by calculating the number of times its articles are cited.
I like your summary, analysis and take home messages.
Moreover, I do agree with your level of evidence that you have assigned to this article: IV. ’.
I do appreciate professor
Summary
Introduction
This article is surrounding COVID 19 infection in kidney transplant recipients. Fever, cough, and hypertension are the most common presenting features. Lab investigations mainly revealed lymphopenia, high CRP, and high ferritin level. This infection is especially important when it comes to kidney transplant recipients because of the high risk of infection that recipients have from the intense long term immunosuppression and associated comorbidities.
This report and conclusions are based on 8 COVID 19 cases in kidney Transplnt recipients from Sheffield Kidney Institute in the UK.
Discussion
Transplant recipients are at high risk of infection due to many reasons, the major of which include immunosuppression, underlying CKD, associated comorbidities, and underlying hypertension and diabetes. Malignancy is a possible consequence of transplant.Incidence of malignancy among COVID 19 patients is close to 1% according to the data mentioned in this study.
The given study found that there is a higher frequency of kidney disease among COVID 19 patients. These may present as hematuria, proteinuria, and high serum creatinine. The reason behind kidney disease in these patients could be attributed to a possible cytokine storm syndrome being induced by the virus. Direct renal injury is also possible. The kidney could very well be the target of the virus. Due to this, treatment would include continuous renal replacement therapy (RRT) because this would consistently flush out the inflammatory cytokines such as tumor necrosis factor – alpha, IL-6, and IL-1Beta. All of these cytokines are involved in renal injury, and RRT plays a role in preventing such injury.
Lab investigations revealed lymphopenia and high CRP levels in these patients. It is possible that there is a link between lymphopenia and ARDS. Low lymphocyte or WBC count could be an indicator of fatal outcome.
IL-6 is considered as a unique biomarker for COVID-19 infection. Increased levels of this marker is associated with high risk of mortality. However, the sensitivity and specificity of this marker is still under study.
In terms of imaging, chest X-ray is seen as the predominant investigation for this infection. Bilateral patchy consolidation is found in most affected patients, however, it is also possible for infected patients to have no classical changes. It is essential to remember that CT for all these patients can burden the radiology department and even lead to temporary unavailability of CT services since decontamination has to take place. A good solution for this would be to use portable X-ray machine instead. British Society of Thoracic Imaging has issued guidelines stating that CT is not to be used unless there is high suspicion with normal or uncertain appearance of CXR in seriously ill patients.
Treatment would include cessation of anti-proliferative drugs such as azathioprine and MMF while monitoring the patient closely in case of severe infection. Corticosteroid therapy can be continued, with cessation of CNIs in those patients requiring mechanical ventilation. Treatment has to be individualized for each patient, particularly in the absence of clear UK guidelines or recommendations for COVID-19 transplant recipients.
The article finally recommends remdisivir as treatment for COVID-19 infection in this cohort of patients. However, since its interaction with CNIs is yet unknown, it is better to administer this drug and monitor any changes in a hospital setting.
Conclusion
Among the COVID 19 patients in the study, the most common and frequent symptoms were fever and cough. The study found that transplant recipients do not behave differently when it comes to COVID 19 infection in comparison with the general population. Supportive treatment would be sufficient in most cases, and should be part of first line management. Self isolation on discharge can help greatly in reducing the burden on health care workers and the public.
Level of evidence
This is a narrative article, and thus level of evidence is 5.
Impact factor of journal
Impact factor is a measure of the frequency with which the average article in a journal has been cited in a given year. This measures the importance or rank of the journal by calculating the number of times its articles are cited.
Impact factor can be calculated based on a two year period, and involves dividing the number of times articles in the journal were cited by the number of articles that citable.
Reference
University of Illinois. Measuring your impact : Impact factor, citation analysis, and other metrics: Journal impact factor (IF). 2023.
Available form : https://researchguides.uic.edu/if/impact
I like your summary, analysis and take home messages.
Hower, I do NOT agree with your level of evidence, called ‘narrative review’.
Yes professor, I would like to correct it to level of evidence 4 since this is a case report/series.
Please summarise this article.
Introduction
o Coronavirus disease 2019 (COVID-19) infection, emerged in Wuhan city, China, in December 2019, has close genomic structural similarities with the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused the SARS pandemic in 2003 and the middle east respiratory syndrome coronavirus (MERS-CoV) that caused (MERS) epidemic in 2012
o By April 26, 2020, infections related to COVID-19 affected people from 210 countries and caused 203,818 reported deaths worldwide
o Aim of the study: manage COVID-19 disease in renal transplant patients (8 cases of COVID-19 infection in kidney transplant patients from Sheffield Kidney Institute, UK)
Case Reports
Patient 1: a 21-year-old female presented with fever but no respiratory symptoms. She is lethargic and generally unwell. Clinical examination was unremarkable, and the chest X-ray was clear. Urine and blood cultures were negative. A nasal and throat swab for COVID-19 tested positive. She is hypertensive. She was on prednisone, tacrolimus, and MMF. She was admitted and received supportive treatment. MMF was discontinued and discharged after 2 days with full recovery and stable kidney functions
Patient 2: a 71-year-old male with hypertensive nephropathy. His baseline Cr was 240–260 μmol/L. His immunosuppressive regimen included prednisolone, tacrolimus, and MMF. He presented 4 years after transplantation with a dry cough with no other symptoms but stable vital signs. Chest X-ray revealed a patchy bilateral consolidation. He was tested positive for COVID-19 nasal and throat swab. MMF discontinued and received supportive treatment. He was discharged 2 days later with stable kidney functions
Patient 3: a 50-year-old male with a history of Wegner’s granulomatosis. He presented two months after transplant with productive cough and was tested positive for SARS-CoV-2 RNA despite unremarkable clinical examination. The chest X-ray was clear, and kidney function tests were stable. His immunosuppressive drugs were prednisolone, tacrolimus, and MMF. The management included discontinuation of MMF, reduction of tacrolimus dose, and self-isolation at home
Patient 4: a 63-year-old male with a history of IgA. He is hypertensive. He presented 15 years latter with fever and AKI. The chest X-ray showed patchy bilateral consolidation, and SARS-CoV-2 RNA was positive. Blood culture was positive for staphylococcus aureus. CRP was 175 mg/L, and serum ferritin was 929 μg/L. His immunosuppressive regimen was prednisolone, tacrolimus, and MMF. The patient was admitted and received IV broad-spectrum antibiotics and paracetamol. We stopped MMF and increased the tacrolimus dose. Kidney function tests improved. The patient recovered and discharged home after 7 days
Patient 5: A 47-year-old female with bronchial asthma. She was maintained on prednisolon, tacrolimus, and MMF. She presented a few months later with dry cough and shortness of breath but no fever. Chest X-ray revealed bilateral middle and lower zone consolidation. Nose and throat viral swabs for COVID-19 were positive. Kidney function tests showed AKI, and mild proteinuria. Microbiology workup showed positive urine culture for E. coli and negative blood culture. Serum CRP on admission was 344 mg/L and ferritin 2684 μg/L, with leukocytosis and lymphopenia. She was tachypnoeic with a respiratory rate of 36, and the peripheral oxygen saturation was 80%, therefore admitted to the ITU for non-invasive ventilation. Her respiratory functions got worse, and she required intubation and invasive ventilation. Bronchoalveolar lavage showed moderate growth of aspergillus. She received broad-spectrum antibiotics and antifungals. No specific antiviral drugs were given. MMF was discontinued. Her kidney functions deteriorated, and she became anuric; therefore CVVH was commenced. After 14 days, she was weaned off mechanical ventilation and transferred from the ITU to the medical ward. Her kidney functions improved and CVVH stopped. She was discharged 7 days later
Patient 6: A 71-year-old female with type II diabetes. Her immunosuppressive therapy included prednisolone, tacrolimus, and MMF. She presented 5 years after transplant with only fever. Chest X-ray showed bilateral peripheral mid and lower zone consolidation. Nasal and throat swabs were positive for COVID-19 RNA. Kidney function tests showed no change from baseline, and microbiological tests were negative. Serum CRP was 19 mg/L, while serum ferritin was 1,835 μg/L. She was admitted to the medical ward for supportive treatment. MMF was discontinued and discharged after 4 days with full recovery
Patient 7: A 40-year-old female with hypertension. She is maintained on prednisolone, tacrolimus, and MMF. Three years after transplant, she presented with fever and dry cough. Nose and throat swabs for COVID-19 RNA were positive. Kidney function tests were stable and microbiological analyses were negative. She was admitted to the medical ward. MMF was discontinued and supportive treatment was initiated. Patient discharged after 4 days with full recover
Patient 8: A 38-year-old male with a failing kidney transplant from June 2013 presented with productive cough and shortness of breath for 2 days. He was maintained on prednisolone, tacrolimus, and azathioprine. On admission on March 20, he had tachypnoea and hypoxaemia with oxygen saturation of 89% on room air (improved to >96% on 4 L/min oxygen through a nasal cannula). Nasal and throat swabs were positive for COVID-19 RNA. Kidney function tests remained unchanged despite the high baseline Cr. Chest X-ray revealed bilateral infiltrates. Management included discontinuation of azathioprine, reduction of tacrolimus dose, and increase of prednisolone dose to 15 mg OD. He did not require any dialysis. Oxygen saturation recovered to >95% on room air, and the patient was discharged after 2 days
Discussion
o Eight cases of kidney transplant recipients infected with COVID-19 (median age = 48.5 years; range = 21–71 years), including 4 males and 4 females
o The most common initial symptoms were fever and cough
o The most frequently associated comorbidity was hypertension
o The main radiological investigation was a portable chest X-ray
o All patients had lymphopenia and high CRP
o Seven patients required hospital admission and only one patient managed as an outpatient
o Management included supportive treatment and discontinuation of the antiproliferative immunosuppressive drugs
o Currently, the US Food and Drug Administration investigates the efficacy of convalescent plasma as a treatment option for patients with severe COVID-19 infection
o Remdesivir (a broad-spectrum antiviral nucleotide prodrug) can be effective against MERS-CoV and SARSCoV infections
o The Adaptive COVID-19 Treatment Trial proved that remdesivir-treated patients had 31% faster time to recovery when compared to control
Conclusion
o The presentations of COVID-19 infected renal transplant patients is the same as in the general population (fever and cough were the most frequent symptoms)
o No evaluation of the effect of immunosuppression on the course of the disease in this case series as the sample size is small
o Supportive treatment could be sufficient or at least to be tried first
o Clinical examination supported by simple bedside measures such as oxygen saturation and portable CXR rather than CT scan, could be enough and limit the spread of infection
o Short hospital stay with self-isolation on discharge, reduces the burden on the health service and protect the staff and the public
o Remdisivir which was approved for the treatment of COVID-19 interacts with CNI (remdisivir should be restricted in a hospital setting where CNI drug level monitoring is available)
What is the level of evidence provided by this article?Level IV (case series)
What is meant by the impact factor of a journal?o The impact factor (IF) is frequently used as an indicator of the importance of a journal to its field and to measure the frequency with which the “average article” in a journal has been cited in a particular time period
o The IF of a journal is not associated to the factors like quality of peer review process and quality of content of the journal, but is a measure that reflects the average number of citations to articles published in journals, books, thesis, project reports, newspapers, conference/seminar proceedings, documents published in internet, notes, and any other approved documents
o Journal which publishes more review articles will get highest IFs
o Journals with higher IFs believed to be more important than those with lower ones
o Impact factor can be calculated after completing the minimum of 3 years of publication; for that reason journal IF cannot be calculated for new journals
o The journal with the highest IF is the one that published the most commonly cited articles over a 2-year period
o IFs are calculated each year by Thomson scientific for those journals that it indexes, and are published in Journal Citation Reports (For example, if a journal has an IF of 3 in 2008, then its papers published in 2006 and 2007 received three citations each on average in 2008)
o The IF of any journal is calculated by the following formula:
Year impactfactor =A/B
A is the number of times articles published in the previous two years were cited by indexed journals during 2012
B is the total number of citable items like articles and reviews published by that journal in the previous two years
Reference
1. Sharma M, Sarin A, Gupta P, Sachdeva S, Desai AV. Journal impact factor: its use, significance and limitations. World J Nucl Med. 2014 May;13(2):146. doi: 10.4103/1450-1147.139151. PMID: 25191134; PMCID: PMC4150161.
. I like your summary, level of evidence, analysis and conclusions.
Covid-19 in Renal Transplant Recipients;
Introduction
Covid-19 virus is a new coronavirus disease in 2019 that emerged in China (December 2019).
8 cases were studied in the transplant recipients with covid-19 infection in Sheffield Kidney Institute, UK.
The median age of patients was 48.5 years (21 to 71 years), including 4 males and 4 females.
3 patients had transplantation within the last 3 months, and the remaining transplanted for over 1 year.
The initial symptoms were
All 8 patients received prednisolone and tacrolimus, 7 received MMF and 1 received AZA.
2 patients develop AKI, (1 required CRRT).
All patients had lymphopenia and high CRP.
3 patients had high ferritin and 1 patient had an elevated IL-6.
A portable x-ray was clear of 2 of the patients and the rest had a picture of viral pneumonia.
1 managed as an outpatient and advised for home isolation, the others required hospital admissions, and 1 required ITU admission, where she need mechanical ventilation, with bronchoalveolar lavage show aspergillosis for which she received antifungal treatment.
The remaining patients (1 need O2 ) and the other need supportive renal treatment, with or without O2 therapy.
Anti-proliferative management D/C in all patients.
Risk factors for infection in transplanted case;
The fatal outcome associated with
6 patients had multiple comorbidities (HTN, T2DM, Bronchial asthma, and a history of cancer).
Pathogenesis of AKI in covid-19 infection is unclear but it can be due to
CRRT showed promising results in patients with SARS and MERS.
Treatment
Conclusion
Level of evidence
Level ((V))
The impact factor of the Journal
Is the number of times articles of the journal published in the past 2 years have been cited in the JCR year.
The impact factor is calculated by dividing the number of citations in the JCR year by the total number of articles published in the previous 2 years.
Level V for case series?
thank you Prof.
Level ((IV))
Yes. level 4
Thank you Kamal
This study is a case series – Level of Evidence IV
Introduction
The spread of SARS CoV 2 quickly affected several countries and initially, there was little data. This study reports eight cases of kidney transplantation with COVID 19
Clinical cases
Patient 1 – Deceased donor to a 21-year-old woman with fever, respiratory symptoms, and normal chest X-ray. Tacrolimus 4mg + MMF 500mg + Prednisone 5mg.
MMF was suspended and discharged with stable renal function
Patient 2 – Male, 71 years old Tacrolimus 6.4 + MMF 500mg + Prednisone 5mg with pulmonary consolidations on chest X-ray. He discontinued MMF and was discharged two days later with normal renal function.
Patient 3 – 50-year-old male with recent living donor and cough. Normal X-rays and stable renal function using Tacrolimus 13.4 + MMF 1g + prednisone 5mg. He suspended mycophenolate and went home.
Patient 4 – Male, 63 years old, deceased donor. Fever and acute kidney injury with bilateral pulmonary consolidation. Tacrikunys 2.7 + MMF 1g + Prednisone 5mg. He increased the dose of tacrolimus and suspended the MMF with improvement in renal function, and he was discharged after seven days.
Patient 5 – a 47-year-old woman with a recent deceased donor with Tacrolimus 5-7 + MMF 500mg + Prednisone 5mg. He presented respiratory symptoms but without fever, with alteration in the X-rays and evolution with consolidations. Evolved with proteinuria and acute kidney injury. Elevated IL6. He presented worsening breathing patterns and intubation when MF was suspended. She improved her kidney function, was extubated, and discharged 21 days later.
Patient 6 – Female 71 years old deceased donor using tacrolimus + MMF + prednisone with fever and no other symptoms. X-rays with alteration and consolidation. There was no change in renal function and MMF was suspended with hospital discharge after four days
Patient 7 – 40-year-old female deceased donor using tacrolimus + MMF + Prednisone with fever and dry cough. Suspended MMF and discharged after four days.
Patient 8 – 38-year-old male with loss of renal function and productive cough. She uses Tacrolimus + Azathioprima and prednisone.
Discussion
Of these patients, only one had the need for hemodialysis again. Chest X-rays were normal in two cases and altered in the others. Only one patient required intubation, but he recovered his respiratory status and renal function. One of the patients evolved to CAPA (Post COVID Pulmonary Aspergillosis). All patients discontinued the antiproliferative.
Transplanted patients have more risks and comorbidities that favor more severe conditions. Five patients had fevers and five had coughs. Two patients had acute kidney injuries, one requiring dialysis.
All patients with lymphopenia and elevated protein C reacted. Serum ferritin and IL6 were measured in a few patients, but all had high values.
Despite the small number of cases, discontinuing antiproliferative drugs is highly recommended. Maintaining corticosteroid therapy is recommended.
Conclusion
Tomography seems to be the best diagnostic test. The use of Remdesivir looks promising, but its interaction with calcineurin inhibitors is unknown, so it is important to monitor the drug during its use.
Thanks
What is meant by the impact factor?
Impact Factor is a method used to rank scientific journals based on the citations they receive. The calculation is made by adding the citations of articles received in the year of calculation of the impact factor and dividing this number by the number of articles published in the two years preceding this calculation.
Thanks, Filipe
COVID-19 in Renal Transplant Recipients:
Case Series and a Brief Review of Current
Evidence
==================================================================
Please summarise this article.
Introduction
Case Reports
Patient 1
Patient 2
Patients 3, 4, and 5 received live donor kidney transplants in February 2020, February 2019, and December 2019 respectively.
Patient 6:
====================================================================
Discussion
==================================================================
Conclusion
====================================================================
What is the level of evidence provided by this article?
The level evidance is IV
==================================================================
What is meant by the impact factor of a journal?
–
====================================================================
Reference
Thanks
Please summarise this article.
Introduction:
The new coronavirus disease 2019 (COVID-19) infection, emerged in Wuhan city, China, in December 2019.
COVID-19 has close genomic similarities to SARS-CoV and MERS-CoV, causing 203,818 reported deaths worldwide.
COVID-19 in kidney transplant recipients has a high risk of infection due to immunosuppression and comorbidities.
This article presents an 8 case series with review of COVID-19 virus infection, 7 of them received tacrolimus+MMF+ prednisolone, with different comorbidities.
Two of them experienced AKI, most had lymphopenia with two with profound lymphopenia.
Discussion:
Median age in these 8 cases is 48.5 years.
The most common initial symptoms were fever and cough.
Blood results showed lymphopenia, high CRP, elevated ferritin, IL-6, and a portable chest X-ray (normal in two of patients), with 6 patients with pneumonia.
Antiproliferative immunosuppressive drugs were discontinued for all patients.
Transplant patients are at a high risk of infection due to multiple risk factors, including immunosuppression, CKD, and comorbidities, such as hypertension and diabetes.
Lianget al. reported that 1% of COVID-19 patients had a history of malignancy, higher than the overall Chinese population.
The incidence of AKI in COVID-19 patients is low, but recent studies have shown a higher frequency of renal abnormalities, suggesting a cytokine storm syndrome or direct renal injury. Continuous renal replacement therapy may play a role in the management of AKI.
COVID-19 infection is associated with high CRP levels, which can lead to adverse outcomes such as ARDS development, myocardial damage, and death. Serum ferritin is an acute-phaseprotein, but its sensitivity and specificity are unknown.
IL-6 is a novel biomarker for COVID-19 diagnosis, but its sensitivity and specificity are unknown, and there is no clear evidence of its use in treatment.
CT decontamination may disrupt radiology service availability, so portable chest X-ray should be considered to reduce transmission of infection. CT should not be used unless there is high suspicion of CXRin a seriously ill patient.
The small sample size of this study cannot give firm recommendations, but suggests discontinuation of antiproliferative drugs while monitoring the patients closely in cases of severe infection. Treatment should be individualized based on individual assessment of each patient.
The US Food and Drug Administration has authorized the use of remdesivir as a treatment option for hospitalized COVID-19 patients due to its promising results.
Conclusion:
The presentations of COVID-19-infected renal transplant patients were similar to the general population, with fever and cough being the most frequent symptoms. Supportive treatment should be tried first, and short hospital stay with self-isolation on discharge reduces the burden on the health service and protects the public.
What is the level of evidence provided by this article?
Level of evidence IV – case series.
What is meant by the impact factor of a journal?
Impact factor = average article cited x specific time period (previous two years).
IF 2023 = articles cited in 2021&2022 divided by total articles published in 2021&2022.
it measures the frequency with which the “average article” in a journal has been cited in a particular time period. Journal which publishes more review articles will get highest IFs.
Thanks
Summary:
Introduction:
The novel COVID-19 infection, which arose in Wuhan, China, in December 2019, has genetic structural similarities with the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused the 2003 SARS pandemic and the 2012 MERS pandemic. COVID-19 infected 210 nations and killed 203,818 persons till April 26, 2020.
Discussion:
Immunosuppression, CKD, and comorbidities such as hypertension and diabetes put transplant patients at risk of infection. Four had hypertension, one had type II DM, one had bronchial asthma and aspergillosis, and one had malignancy. Numerous COVID-19 research studies examined similar comorbidities. These investigations found that hypertensive, diabetic, and COPD patients had double- and five-fold infection risks, respectively.
All patients exhibited lymphopenia and elevated CRP. Guan et al. found lymphopenia in 83.2% of infected patients on admission. Another study linked lymphopenia to ARDS. Two other studies found that patients with low lymphocyte/white blood cell ratios on entry and after hospitalization died.
Several studies linked COVID-19 to elevated CRP. found that 60.7% of patients had increased CRP, with severe cases having higher levels than non-severe ones.
6 patients discontinued their antiproliferative medicines and underwent supportive care; 1 needed oxygen therapy and one needed mechanical breathing. No patients got particular antiviral medications. COVID-19 in renal transplant patients should consider age, degree of infection, post-transplant length, comorbidities, tissue mismatch, and rejection events while administering immunosuppression. With minor infections, immunosuppressive medications are usually continued or reduced.
Conclusion
Fever and cough were the most common symptoms in COVID-19-infected kidney transplant patients. The COVID-19 infection in our transplant patients was similar to the overall population. We couldn’t assess immunosuppression’s impact on disease progression due to the limited sample size, but it didn’t hurt. Based on our expertise, supportive therapy may suffice or be attempted initially. Clinical evaluation backed by bedside measurements like oxygen saturation and portable CXR rather than a CT scan may be adequate to minimize infection.
Level of evidence: IV
IF: the factor of influence It is usual practice to utilize the impact factor (IF) of a journal in order to quantify the frequency with which the article in the journal has been referenced in a certain amount of time and to evaluate the relative relevance of a journal within its own discipline. Journals that publish a greater number of review papers will have higher impact factors.
Thanks
–Summary
Introduction
COVID19 virus that appeared in China December 2019 had genotypic features similar to SARS which caused SARS pandemic 2003 and MERS epidemic 2012.
COVID lead to 203,818 reported deaths all over the world.
Renal transplant recipients on long term immunosuppressives are at greater risk of infections.
This is a case report of 8 kidney transplant recipient cases infected with COVID-19.
This case report included 4 males and 4 females. Most cases had hypertension as a comorbidity, manifesting with fever and cough.Portable chest X-ray was done for the cases.
Most cases lab showed lymphopenia, high C-reactive protein, and extremely elevated ferritin level.
1 case was treated on outpatient bases ,the other 7 cases required hospital admission, and 1 needed ICU admission and mechanical ventilation ,BAL was done confirming aspergillosis and antifungal therapy was given
Management was mainly supportive treatment as intravenous fluid therapy, following kidney function oxygen therapy as needed and antiproliferative immunosuppressives were stopped.
The 7 cases were recovered and were sent for home isolation.
Home isolation was the best option to decrease burden on hospitals and to limit spread of infection.
Discussion
Transplant recipients are at a high risk of infection because of immunosuppression, CKD, and associated comorbidities particularly hypertension and diabetes.
Studies demonstrated that hypertension and diabetes have a double-fold infection risk and COPD patients have a 5-fold higher risk.
1 case had post transplant malignancy which was adenocarcinoma of sigmoid colon in concordance with Liang et al stating that COVID-19 patients had a
higher malignancy history compared to cancer prevalence in the overall Chinese population and the most common malignancy was cancer lung.
The mechanism of renal involvement is not clarified yet, but cytokine storm syndrome or direct renal injury by the virus were suggested.
CRRT revealed favourable outcomes in treatment of AKI associated with SARS and MERS.
It was suggested that inflammatory cytokines can be eliminated by high-volume hemofiltration.
Another study shed light on the possibility of a connection between lymphopenia and ARDS occurrence.
It was demonstrated that low lymphocyte/WBCs ratio had fatal outcomes.
The current study mentioned that high CRP and ferritin can be associated with poor prognosis .
Elevated IL6 level is accompanied with high mortality risk.
The British Society of Thoracic Imaging (BSTI) guidelines stated that CT is not recommended except if COVID is highly suspicious with normal or uncertain appearance of CXR in severely ill cases.
When manipulating immunosuppressives in such cases many aspects have to be considered as comorbidities ,age ,infection degree and rejection attacks.
For cases with mild infections, the immunosuppressives can be continued or reduced .
It is advised to stop antiproliferative drugs with close follow up in severe infection.
While for critically ill cases in need of ventilation ,CNI discontinuation is debatable and steroids can be continued.
Remdesivir is effective against MERS-CoV and SARSCoV infections with favourable outcomes.
FDA authorised Remdesivir use for hospitalised COVID patients.
Conclusion
Covid infected renal transplant recipients were similar to general population.
–Level of evidence is 4 because it is a case report
–Impact factor is a measure of the frequency where the average article in a journal had been cited in a certain year. It is used to measure the importance or rank of a journal by calculating the times its articles are cited.
Thanks
Many thanks for you Prof.Halawa
1- New COVID19 corona viruses has multiple presenting pictures in the patients especially immunosuppressed patients.
2- It is structurally similar to SARS-COV, and MERS-CO viral infection.
3- Can presented by fever which is important symptom, dry cough.
4- CXR may be clear or revealed consolidating patch or infiltration.
5- So, and clinical suspicion for COVID19, nasopharyngeal swab and PCR should be done to confirm or exclude the diagnosis.
6- Management includes general supportive measures like hospitalization, hydration, lab investigations.
7- As regard immunosuppressive medications; MMF should be reduced or discontinued, same dose CNI and steroid.
8- CNI should be reduced in severely ill patients
9- Convalescent plasma – derived from the blood of recovered patients could be used as a treatment option in severe cases.
10- Remdesivir is antiviral drug used to enhance recovery in hospitalized patients
level 4 of evidence
impact factor IF of journal is commonly used to evaluate the relative importance of a journal within its field and to measure the frequency with which the “average article” in a journal has been cited in a particular time period. Journal which publishes more review articles will get highest IFs.
Mohit Sharma, Anurag Sarin, Priyanka Gupta, Shobhit Sachdeva, Ankur V. Desai. Journal Impact Factor: Its Use, Significance and Limitations. World J Nucl Med. 2014 May-Aug; 13(2): 146.
Thanks, Riham
Please summarise this article.case series for 8 cases of kidney transplant recipients infected with COVID-19
submitted earlier in the pandemic : June 17, 2020 which was cited 28 times (per google scholar) – checked 18 March 23. Authors reported their experience with 8 cases from preesntation, investigationsa and CXR. The treatment was supportive while holdling antimetabolites.
What is the level of evidence provided by this article? Level IV according to Oxford system For Evidence Levels:
What is meant by the impact factor of a journal?it is the frequency of citation of the average article in a particular year. It measures the rank of a journal by calculating the times of citations.
It’s calculated number of citations/number of articles – in the 2 years previous to the year of calculation.
Thanks, Ahmed
Please provide a summary?
Introduction:
Cases:
Discussion:
Level of evidence is 5
Impact factor:
Is the measurement of journal citation frequency in a particular year, it calculated based on 2 year period & dividing number of articles citing by number of articles that are citable.
Thanks, Ban
Why level 5 evidence? please explain.
I depend on this figure