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 a productive cough and 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.
How would you manage this case?
A. Hospitalization and isolation
B. Monitoring i.e RR, HR, SpO2, hydration, urine output
C. Investigation
– CBC, CRP
– RFT, LFT
– Tacrolimus drug level
– D- dimer, IL- 6 level
– HRCT of chest
– Blood & Urine C/S
D. Supportive treatment i.e adequate hydration, respiratory support as require
E. Modification of immunosuppression (Stop MMF, tacrolimus trough level 4-6 ng/dl, if require oxygen increase dose of prednisolone)
F. Thromboprophylaxis
G. Remdicivir and dexamethasone in case of requiring respiratory support
Substantiate your answer
Though this is mild case, require hospitalization and thromboprophylaxis as this is high risk patient.
What is the role of anticoagulant in post-transplant COVID infection?
According to ACH society Anti coagulation is recommended in COVID infected patients with moderate to severe infection.
Also those already on antiplatelet and anticoagulation should be continued.
How to manage this case with COVID-19?
Will advise admission,
General management,
Like IV fluid,
Antipyretics,
Multivitamins,
Prophylactic antibiotic to prevent super-infection,
High dose steroid,
Antiviral,
If high IL6 then Tocilizumab,
Immunosuppression dose reduction.
References;
1. https://www.nejm.org/doi/10.1056/NEJMoa2021436, N Engl J Med 2021; 384:693-704 DOI: 10.1056/NEJMoa2021436.
2. https://academicworks.medicine.hofstra.edu/publications/6200/.
Sir i would start anticoagulation, just to keep in mind the drug interaction.
Second, there is patch on right middle zone involving upper part of lower zone too.
I will hospitalize for further workup and treatment.
Management Live donor renal transplant recipient, on triple immunosuppression, high Tac C0 level. Presented with cough, tested positive for COVID Clinical examination unremarkable – check respiratory rate, SpO2. HRCT chest – helps risk stratification and Tt planning. Get CBC (Leucopenia, Thrombocytopenia) – to adjust drug doses. baseline RFT, LFT, LDH, CRP, D-dimer should be checked This patient being clinically stable – needs just home isolation, with advises for observing breathing difficulty. Routine check-up of all vital signs, temperature, tachypnoea and oxygen saturation. Patient can be in contact with treating team through telemedicine / telephonic consultation. Mild to moderate illness with Spo2 >95% à need only monitoring. High fever >4 days, hypoxia < 94% on room air needs admission to hospital, especially in high-risk cases (transplant patients) IS Reduction: withhold MMF till recovery, Tacrolimus dose reduction, targeting C0 of 7-9; increase Prednisone to 10mg OD. Treatment: drugs like macrolides, HCQS, Convalescent plasma are not recommended by ICMR (Indian council of medical research) Hypoxic patients à Dexamethasone 6 mg IV OD x 7-10days prevents lung inflammation IL6 levels monitored – indicator of cytokine storm syndrome (2nd week) – Tocilizumab is recommended for elevated IL6 levels with cytokine storm Anticoagulants – recommended for moderately to severe COVID – with anticoagulants with LMWH and later oral anticoagulants for 6 to 12 months REFERENCES: 1 – NIH; COVID 19 treatment guidelines, last updated Dec 1 2022.
2 – Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron 2021; 145(2): 192-198 doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980. 3 – RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595. 4 – Santana ANC, Takagaki TY, Barbas CSV. Incidence of fatal venous thromboembolism in antineutrophil cytoplasmic antibody-associated vasculitis. J Bras Pneumol. 2011;37(3):409-411
Dear All What is the role of anticoagulation in the management of post-transplant COVID infection? What about hospitalisation? by Prof. Ahmed Halawa What is the role of anticoagulation in the management of post-transplant COVID infection? in For Covid-19 symptomatic – moderate to severe, and critically ill patients – anticoagulation has been recommended, as in any acutely ill, hospitalized patient (1). This is important in COVID patients, also because of high association with thrombotic complications that lead to PET, NI, stroke and adds to mortality. As per BTS guideline – all patients admitted for COVID-19 should be assessed for anti-thrombotic prophylaxis, and majority would require anticoagulant. LMWH in therapeutic dose be used for patients requiring supplemental oxygenation; lower doses should be used in critical patients (on high-flow oxygen, CPAP, NIV or invasive ventilation) without any indication of therapeutic anticoagulation (2). For Outdoor / home isolation patients Those at risk of possible ischemia or infraction like PE, DVT à consider LMWH (unfractionated heparin if GFR <15ml/min); fondaparinux is preferable in patient with h/o of HIT. (4) Patients already on anticoagulants, (for AF or VTE) à continue previous anticoagulants or switch to short acting agents in case of admission to hospital for COVID-19 infection, D-Dimer positive. (4-6) Indications of hospitalisation for Covid-19 patients: The indications for hospitalization in a COVID-19 patient include (3): 1. A room air oxygen saturation of <94% 2. Respiratory rate of >30. 3. PaO2/FiO2 <300 mmHg 4. Lung infiltrates >50% References: 1. Chandra A, Chakraborty U, Ghosh S, et al. Anticoagulation in COVID-19: current concepts and controversies. Postgrad Med J. 2022 May; 98(1159): 395-402. doi: 10.1136/postgradmedj-2021-139923. 2. BTS Guidance on Venous Thromboembolic Disease in patients with COVID-19. Updated August 2021. British Transplantation Society. Available online: https://www.brit-thoracic.org.uk/document-library/quality-improvement/covid-19/bts-guidance-on-venous-thromboembolic-disease-in-patients-with-covid-19/ 3. Covid-19 treatment guidelines. Available online: 4. https://files.covid19treatmentguidelines.nih.gov/guidelines/covid19treatmentguidelines.pdf 5. UpToDate 6. Schulman S, Sholzberg M, Spyropoulos AC, et al. ISTH guidelines for antithrombotic treatment in COVID-19. Journal of thrombosis and haemostasis: JTH. 2022 Oct;20(10):2214-25. PubMed PMID: 35906716. 7. Cuker A, Tseng EK, Schünemann HJ, et al. American Society of Haematology living guidelines on the use of anticoagulation for thromboprophylaxis for patients with COVID-19: March 2022 update on the use of anticoagulation in critically ill patients. Blood advances 2022 Sep 13; 6(17): 4975-82. PMCID: PMC9236618.
Thrombotic complications (arterial and venous) are common in patients admitted to hospital with COVID-19 and are an independent predictor of poor outcome.1 Microvascular thrombi also contribute to organ dysfunction, including acute respiratory distress syndrome.
The pathogenesis of thrombosis in COVID-19 is intimately linked with the inflammatory response to the virus, endothelial infection, activation, and injury as well as hypercoagulability.2 Recognition that thrombosis is a key contributor to clinical deterioration and death has led to global interest in whether escalated anticoagulation dose or extended duration improves patient outcomes.
Early in the COVID-19 pandemic, published guidelines were heterogeneous with some, in the absence of evidence, recommending increased anticoagulation doses (particularly in critical care), stratifying dose by D-dimer results, or extended post-discharge thromboprophylaxis, or both.3 Since then, randomised controlled trials have focused on all phases of illness—from the community, to hospital admission, when critically ill, and post-hospital discharge—so that high-quality evidence is now informing clinical practice. From these trials, it has become clear that efficacy and safety of antithrombotic treatments depend on timing with respect to illness severity and dose, and that the mechanism of action might also be important.
For non-critically ill patients hospitalised with COVID-19, therapeutic-dose heparin appears beneficial, with a high probability of reducing the need for organ support and the progression to intubation and death, regardless of D-dimer results
.4 Results from two subsequent randomised controlled trials have also supported the role of therapeutic-dose heparin in this cohort.5, 6 By contrast, in critically ill patients, therapeutic-dose heparin did not improve outcomes and there was a high probability of harm.7 The INSPIRATION trial did not demonstrate benefit of intermediate-dose heparin compared with conventional low dose in this critically ill patient group.8 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02503-4/fulltext
SARS COV19 viral infection post transplantation is commonly associated with grim prognosis attributed to immunosuppressive status. The disease might progress to severe respiratory disease with respiratory failure culminating in higher mortality and morbidity. Similarly, AKI risk is mounting in post-transplant patients infected with Covid 19 virus. However, management is entirely dependent on severity of presentation. In our patient as far as he is stable with no respiratory symptoms, particularly dyspnea or tachypnea and normal chest xray, Themain line of management:
1] self-isolation,
2] close observation, for respiratory symptoms, desaturation and hemadynamic stability.
3] to stop anti-metabolite MMF and reduce dose of Tacrolimus.
4] No indication is there to increase dose of corticosteroid.
5] anti-coagulant prophylaxis is indicated as early as possible due to the higher risk of thromboembolic disease.
6]close observation of renal function as AKI risk is soaring.
in case of clinical deterioration of the patient with dyspnea, tachypnea or desaturation, then admission to hospital is indicated with multidisciplinary plan of care, including close observation of inflammatory markers in addition to clinical status. such as:
1] ferritin
2] CRP more than 120.
3] neutrophil/ lymphocytes count of more than 3/1
4] d-dimer
Reference:
1] http://www.BTS.UK. updated 2020.
· How would you manage this case?
COVID 19 early post transplant, within 2months, in the first few months of COVID 19 era with little experience on that.
Careful history of her illness, duration, recent travel, contact with sick person. His immunological history, history of infection, rejection.
Management should be according to local guidelines, isolation, admission, reduction of immunosuppression (FK level 8-10), hold MMF if low risk of rejection and/or continuous fever or desaturation.
Prophylactic anticoagulation according to local guidelines and personal risk of DVT, as it is known for SARS COV2 to increase risk of VTE.
· Substantiate your answer References MOH KSA local protocols for SARS Cov 2 infection
Q1: patient with a history of Wegner and kidney transplantation infected by SARS-Cov.2 should be admitted to the hospital. Performing complete laboratory tests and HRCT scans. O2 saturation should be measured and if needed should receive supplemental O2. Reduction of immunosuppression by stopping MMF and even reduction of tacrolimus according to its level is recommended. Starting remdesivir for COVID-19 infection and proper antibiotics. Prophylactic anticoagulation should be considered to measure CRP, d-dimer and fibrinogen, and dexamethasone, and if indicated even start tocilizumab.
In the kidney transplant population, considerable proportions who had contracted SARS-CoV-2 developed an acute kidney injury (AKI).
Among 52 case reports reviewed, 63% of patients had been diagnosed with an AKI during their hospitalization.
Predictors of mortality among kidney transplant patients with SARS-CoV-2 infection were generally similar to those of the general population.
In factors specific to kidney transplant recipients, shorter span of time between transplant and COVID-19 infection, deceased donor transplant, diabetes, and previous antirejection therapy were associated with increased mortality.
Active cytomegalovirus coinfection and bacterial coinfections were also shown to complicate and worsen the prognoses of kidney transplant patients.
management – hospital admission in isolation room. -measurement of oxygen saturation , temperature. -Good hydration – Antipyretics , mucolytics. – Lab investigationCBC , CRB , LDH . FERRITIN , D dimmer …etc. -monitor kidney function and ABG.
– stop MPA/MMF due to its implications in suppressing the response of T-lymphocytes needed to mount an immune response to SARS-CoV-2.
-reduce tacrolimus dose to keep trough level 5-7ng/ml
. it was found that in patients who received anti-COVID-19 therapeutics, the tacrolimus doses had to be adjusted due to drug-drug interaction.
– Aspirin prophylaxis is recommended as patients with COVID-19 are at higher risk of blood clots especially in this patent as he had Wegner’s granulomatosis.
– In the treatment of COVID-19 in kidney transplant patients, reports of use of tocilizumab, remdesivir, low-dose methylprednisolone, convalescent plasma therapy, colchicine, and favipiravir have been published. However, most of these positive outcomes were observed in either case studies or small cohorts, and the use of any of these treatments should be considered on a case-by-case basis.
reference
DeFelice, Gina; Vijay, Adarsh,*. Coronavirus-19 infection in kidney transplant recipients: A comprehensive review. Indian Journal of Urology 38(2):p 110-114, Apr–Jun 2022.
· How would you manage this case?At first, it is necessary to classify the patient to define where the follow-up will be: – Mild and moderate cases without comorbidities: it could be conducted on an outpatient basis, with a reduction in the MMF and weekly consultation- Moderate cases with comorbidities (hypertension, diabetes, peripheral vascular disease): patient should be hospitalized, monitored regarding the need for oxygen therapy, MMF suspended, corticoid therapy with dexamethasone and antiviral therapy with remdesivir, prophylactic anticoagulation- Severe case: oxygen therapy, discontinue MMF, start corticosteroid therapy with dexamethasone and antiviral therapy with remdesivir, therapeutic anticoagulation.In critically ill patients, we have an increased risk of pulmonary thromboembolism, but without formal indication of therapeutic anticoagulation due to the risk of bleeding. However, patient with a history of Wegener’s granulomatosis, which adds risk, and anticoagulation is interesting. REFERENCES:
1 – NIH;COVID 19 treatment guidelines, last updated Dec 1 2022. 2 – Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980. 3 – RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595. 4 – Santana ANC, Takagaki TY, Barbas CSV. Incidence of fatal venous thromboembolism in antineutrophil cytoplasmic antibody-associated vasculitis. J Bras Pneumol. 2011;37(3):409-411
The given recipient is a live donor renal transplant recipient with basic disease as GPA…. Patient is on tacrolimus based triple immunosuppression…The patient has presented with cough and has tested positive for COVID…
Detailed clinical examination is needed…Respiratory rate, SPo2 examination to assess for hypoxia…CBC to look for leucopenia…baseline RFT,LFT, LDH, CRP, d dimer should be done…IL6 levels can be monitored as to get prepared for cytokine storm syndome in the 2nd week if any…CT chest for risk stratification should be done..CXR shows some right middle and lower lobe GGO…
The initial management of this patient is basically home isolation…Routine check of all vital signs including oxygen saturation, temperature, and tachypnea…Patient can be in contact through telemedicine facilities as it was done during the pandemic in our hospital…Mild to moderate illness with Spo2>94% need only monitoring..High fever more than 4 days, hypoxia < 94% on room air needs hospital admission especially in high risk cases like renal transplant patients….
Treatments like macrolides, HCQS, Convalescent plasma are not recommended by ICMR(Indian council of medical research)….
If the patient has hypoxia, we need to give IV steroids Dexamathasone 6 mg IV OD to prevent lung inflammation… Tocilizumab is recommended for elevated IL^ levels with cytokine storm if any
The role of anticoagulants in COVID in renal transplant recipients: Recommended for moderatly to severe COVID ..with anticoagulants with LMWH and later oral anticoagulants for 6 to 12 months
This is a confirmed case of COVID 19 with mild symptoms.
This patient can be treated in out patient basis with proper education about criteria of hospitalization. Isolation, self monitoring of oxygen saturation. These signs are persistent fever, respiratory distress and drop in oxygen saturation. Management:
· Detailed history and clinical examination, history of contact with SARS2-CoV positive patients.
· ABG, O2 Saturation, D-Dimer, HRCT chest, CBC, (lymphopenia may be seen)
Urine Analysis, Urine and Blood C/S
CNI level, Ferritin, IL-6.
· Isolation and close monitoring of oxygen saturation, good hydration, anti pyretic
· Reduction/modification IS: stop MMF with close graft monitoring. Maintain trough level of Tacrolimus 4–6 ng/dL.
· Dexamethasone in those receiving respiratory support
· Anti viral options: Paxlovid, remdesivir, molnupiravir, favipiravir, ribavirin, & Kaletra. References:
·Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
This COVID 19 case has been identified and has mild symptoms. If the patient is properly informed about the requirements for hospitalization, they can be treated on an outpatient basis. Self-monitoring of oxygen saturation in isolation.
Important parameters for determining the COVID-19 stratification includes saturation and signs of respiratory distress.
If the patient has moderate to severe respiratory symptoms, an HRCT or CTPA may be recommended to rule out complications.
Initial step is to reduce MPA or antimetabolite to immunity recovery and self-defense, and the high level of tacrolimus must be adjusted to avoid secondary bacterial infection or nephrotoxicity.
IV hydration to maintain euvolemia
Prophylactic anticoagulation
Empirical antibiotic such as azithromycin could be helpful as immunomodulator.
Steroid is indicated in patients with oxygen requirement or severe cases and during cytokine storm.
Selection of antiviral therapy is given in agreement with ID consultant.
Multiple comorbidities, including cancer, diabetes, tobacco use, pregnancy, tuberculosis, cerebrovascular disease, bronchial asthma, COPD, renal failure, heart failure, and liver failure, are present in patients with multiple comorbidities. >65-year-old have been linked to higher risk of disease progression.
The use of Remdisivir has been shown to decrease viral load, and subsequent viral complications.
In case of cytokine storm (high persistent fever, CRP, D-dimer, hypofibrinogenemia, and high ferritin) –early initiation of dexamethasone 6 mg per day for 10 days.
post transplant covid 19 infection with cough
monitor fever and SPO2
persistent fever 100F and spo2 less than 90% on room aur are bad signs and need hospitalisation
covid 19 is prothrombogenic condition and after hospitalisation will be put on fractionated heparin
Antiplatlets on OPD basis is not not a standard practice
management is mainly supportive and IS is continued
in general recovery is as good as general population if detected in early phase
To admit to the hospital in isolation.
Investigations such as:
· Request HRCT
· Sputum culture rule out supper added infection
· FBC
· Renal function
· Procalcitonin
· CRP
· Ferritin
· D dimer
· Tacrolimus level
· Blood suger
· Liver function test
· Urine microscopy and culture
Reduce Tac dose by 50%, stop MMF
Hydration
Prophylactic anticoagulation
Repeat CXR if condition changes
monitor oxygen saturation
In case condition changed, and the patient requires respiratory support
dexamethasone 6 mg for 10 days
Antiviral Remdesivir should be added.
In case of elevated inflammatory markers (IL) Sotrovimab ( monoclonal antibodies) can be prescribed (if oxygen saturation is not dropped.
References:
Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
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 a productive cough and 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.
History and Physical examination
Routine labs CBC ,Creatinine and BUN, AST ,ALT ,LDH, CRP
Coagulation profile ,RBS ,serum electrolytes, ferritin ,IL6
Tacrolimus level
HR Chest CT
Management included
This patient considered high risk as he is immunocompromised with hx of Wegner’s granulomatosis and he should be hospitalized in isolation room with close
Vital signs spo2 should kept above 94 %
Daily labs to assess rejection
supportive treatment (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.
Decrease Tacrolimus level to reach from 4 to 6 ng/mL
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.
short course of dexamethasone (6 mg once daily for up to 10 days) improved survival in hospitalized people with severe COVID-19 who were mechanically ventilated or who required supplemental oxygen.
Tocilizumab or baricitinib used in combination with dexamethasone is recommended for some patients with severe or critical COVID-19.
Because dexamethasone, tocilizumab, and baricitinib are immunosuppressive agents, patients who receive these medications should be closely monitored for secondary infections.
Therapeutic anticoagulation for transplant recipients who are hospitalized for COVID-19 should be managed similarly to anticoagulation for other hospitalized patients. Patients with platelet counts <50,000 cells/µL should not receive therapeutic anticoagulation to treat COVID-19. Clinicians should follow hospital protocols for managing anticoagulation in patients with thrombocytopenia.
antimicrobials used to prevent or treat opportunistic infections.
Reference
COVID 19 guidelines Special Considerations in Solid Organ Transplant, Hematopoietic Cell Transplant, and Cellular Immunotherapy Candidates, Donors, and Recipients
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 a productive cough and 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.
Issues/ concerns:
– 50yo male, Wegener’s granulomatosis, LDKTx Feb 2020
– April 2020: presented with productive cough, positive SARS-CoV-2 RNA
– imaging: HRCT chest to better assess parenchymal involvement
– assess for risk factors: old age, comorbidities, physical inactivity, male sex, low socioeconomic status, laboratory abnormalities (AKI, lymphopenia, thrombocytopenia, elevated liver enzymes, LDH, CRP, ferritin, IL-6, TNF, D-dimer, prothrombin time, troponins, CPK)
– approach to management is similar to that of the general population i.e., supportive care, use of antiviral medications
– severity of SARS-CoV-2 infection is affected by the type, combinations and intensity of immunosuppression: lymphocyte depleting antibodies and antimetabolites cause lymphopenia which is a risk factor for severe COVID-19 disease, mTORi and MMF decrease immune response to the vaccine
– there is no well-defined/ optimal approach when it comes to modifying the immunosuppressive therapy
– immunosuppressive regimen adjustment should be individualized depending on the disease severity, type of organ transplant, the specific immunosuppressive regimen used, time post-transplant, risk of acute rejection
– reduce or hold the antimetabolite especially in patients with lymphopenia i.e., ALC <700cells/mL
– continue with CNIs since they inhibit IL-1 and IL-6 pathways: Il-1 and IL-6 result in a severe, dysregulated immune response
– mTORi is thought to have some biological activity against SARS-CoV-2
– watch out for drug-drug interactions and the effects on the immunosuppressive therapy: more so with drugs that inhibit or induce CYP3A metabolism and/ or P-gp efflux
– the decision to reduce immunosuppression should be weighed against the risk of rejection
– COVID-19 itself increases the risk for acute graft rejection, an exaggerated intense inflammatory host immune response can contribute to the overall disease severity
– some SOT recipients recover without reduction in immunosuppression but this increases the risk of IRIS and rejection
– continued use of immunosuppression increases the risk of uncontrolled infection
– vaccination: ideal timing for vaccination in the post-transplant period remains unknown, but one can consider vaccinating 1 month post-transplant or 3 months after using ATG (T-cell depleting agent) or Rituximab (B-cell depleting agent)
– requires hospital admission and isolation given his risk factor profile
– baseline investigations and imaging as suggested above
– assess disease severity based on presence of symptoms suggestive of pneumonia, oxygen saturation, respiratory rate, findings on imaging
– monitor oxygen saturation and respiratory rate, oxygen therapy depends on the oxygen saturation
– IV antibiotics if there is a super-imposed bacterial infection
– IV hydration, GI prophylaxis, DVT prophylaxis
– hold MMF, target tacrolimus trough level of 2-4ng/mL, continue with the steroids
– if the patient develops severe disease, transfer to ICU, discontinue all immunosuppressive agent and increase steroid dose to prednisone 15-25mg/day or dexamethasone 6mg BD for 10 days but if the risk of rejection is high, consider low dose CNI
– remdesivir can also be considered: it is thought to reduce the viral load and also the risk of a cytokine storm
– tocilizumab enhances survival in case of a cytokine storm
Substantiate your answer
References
1. Kates OS, Haydel BM, Florman SS, Rana MM, Chaudhry ZS, Ramesh MS, et al. Coronavirus Disease 2019 in Solid Organ Transplant: A Multicenter Cohort Study. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2021 Dec 6;73(11):e4090-e9. PubMed PMID: 32766815. Pubmed Central PMCID: PMC7454362. Epub 2020/08/09. eng.
2. Nair V, Jandovitz N, Hirsch JS, Nair G, Abate M, Bhaskaran M, et al. COVID-19 in kidney transplant recipients. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2020 Jul;20(7):1819-25. PubMed PMID: 32351040. Pubmed Central PMCID: PMC7267603. Epub 2020/05/01. eng.
3. Gérard AO, Barbosa S, Anglicheau D, Couzi L, Hazzan M, Thaunat O, et al. Association Between Maintenance Immunosuppressive Regimens and COVID-19 Mortality in Kidney Transplant Recipients. Transplantation. 2022 Oct 1;106(10):2063-7. PubMed PMID: 35883236. Pubmed Central PMCID: PMC9521383. Epub 2022/07/28. eng.
4. Requião-Moura LR, Modelli de Andrade LG, de Sandes-Freitas TV, Cristelli MP, Viana LA, Nakamura MR, et al. The Mycophenolate-based Immunosuppressive Regimen Is Associated With Increased Mortality in Kidney Transplant Patients With COVID-19. Transplantation. 2022 Oct 1;106(10):e441-e51. PubMed PMID: 35765133. Pubmed Central PMCID: PMC9521389. Epub 2022/06/30. eng.
5. Elsayed HM, Wadee S, Zaki MS, Were AJO, Ashuntantang GE, Bamgboye EL, et al. Guidelines for the prevention, detection and management of the renal complications of COVID-19 in Africa. African Journal of Nephrology. 2020 06/09;23(1):109-26.
This is a confirmed case of COVID 19 with mild symptoms. This patient can be treated in out patient basis with proper education about criteria of hospitalization. Isolation, self monitoring of oxygen saturation. These signs are persistent fever, respiratory distress and drop in oxygen saturation.
Management: · Detailed history and clinical examination, history of contact with SARS2-CoV positive patients. · ABG, O2 Saturation, D-Dimer, HRCT chest, CBC, (lymphopenia may be seen)
Urine Analysis, Urine and Blood C/S
CNI level, Ferritin, IL-6. · Isolation and close monitoring of oxygen saturation, good hydration, anti pyretic · Reduction/modification IS: stop MMF with close graft monitoring. Maintain trough level of Tacrolimus 4–6 ng/dL. · Dexamethasone in those receiving respiratory support · Anti viral options: Paxlovid, remdesivir, molnupiravir, favipiravir, ribavirin, & Kaletra. References: ·Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
Saturation and respiratory distress are important parameters to determine the category of Covid.
O2 saturation and performing Borg scale after 6 minutes to categorize the patient according to severity.
HRCT or CTPA will be indicated when the patient has moderate to severe respiratory symptoms to look for organising pneumonia or pulmonary embolism.
I would reduce the MPA or antimetabolite to aid in cell recovery and high level of tacrolimus needs adjustment to avoid secondary bacterial infection or toxicity with concurrent usage of medications.
The steroid dose will be adjusted to covid protocol in the institution.
Antiviral therapy such as oral nimatrelvir/ritonavir or intravenous remdisvir) will be started after consulting ID physician.
Duration from symptom onset is ≤5 days for nimatrelvir/ritonavir, or ≤ 7 days for remdisvir (patients who are > 7 days from the onset are treated with supportive measures only)
Patients who are at risk of progression to severe disease such as, immunosuppressed (SOT, HIV)Patients with multiple comorbidities like cancer, DM, smoking, pregnancy , TB, cerebrovascular disease, bronchial asthma, COPD, renal failure, heart failure and liver failure. Patients >65 years old Patients > 50 years and unvaccinated will be monitored
Early start of viral RNA inhibitor (remdesivir) to reduce viral load and time in hospitals, and reduce the risk of having a cytokine storm.
IV hydration, anticoagulation for DVT prophylaxis, PPI
IV antibiotics – usually broad spectrum initially
In case of cytokine storm (high persistent fever, CRP,D-dimer, hypofibrinogenemia , high ferritin) –early start of dexamethasone 6 mg daily for 10 days
References
Bitterman R, Kumar D. Respiratory Viruses in Solid Organ Transplant Recipients. Viruses. 2021 Oct 25;13(11):2146.
RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704.
A case of post Kidney transplant with SARS-COV-2 RNA positive and productive cough with history of Wegner’s granulomatosis.
Will need admission for close observation (ABG/O2Sat) and more workup (CT chest, and blood tests to look for severity of disease). In General, we can treat this case with supportive treatment (good hydration and acetaminophen as needed)) and can be managed as outpatient with close follow-up (O2Sat at home) monitoring.
We should classify our patient as per clinical manifestation:
1-Asymptomatic patients
mild disease (oxygen saturation above 93%, no lung involvement on chest computed tomography) needs follow-up in the outpatient clinic weekly.
2-Patients with moderate disease (oxygen saturation above 90%, respiratory rate under 30 breaths/min) needs hospitalization during initial phase and followed up in the outpatient clinic in the later period.
3-Hospitalization in severe disease (oxygen saturation under 90%, respiratory rate above 30 breaths/min), cytokine storm (persistent fever, high or increasing CRP, ferritin, and D-dimer, abnormalities in liver function tests, hypofibrinogenemia with cytopenia in the forms of lymphopenia and thrombocytopenia).
How would you manage this case?
Detailed history and clinical examination
Any history of contact with SARS2-CoV positive patients.
ABCD, ABG, O2 Saturation and D-Dimer
CT thorax without iv contrast to rule out hemorrhage from infection.
CBC, (lymphopenia may be seen)
Kidney function tests.
Urine Analysis, Urine and Blood C/S
CNIs level
TB (Mantoux, IGRA, and sputum culture) Screening
Fungal (PJP) (induced sputum or bronchoscopy for BAL) screening
S.Ferritin, IL-6.
CMV viral load.
LDH, CRP and procalcitonin
Management:
Admission in isolation room, under observation (ABG/ O2Sat)
Supportive medical therapy, good hydration (IV fluids and acetaminophen as needed).
Reduction of immunosuppressive medications or even discontinued.
Discontinued MMFor decrease 50% and continue CNIs with close graft monitoring the patient (immunosuppression treatment should be individualized based on the careful assessment of each patient) Tacrolimus Trough levels adjusted as 4–6 ng/dL. Drugs targeting immune response regulation:
Dexamethasone in those receiving respiratory support (invasive mechanical ventilation or oxygen alone): resulted in lower 28-day mortality Drugs that preventing viral replicatation:
Paxlovid, remdesivir, molnupiravir, favipiravir, ribavirin, & Kaletra.
Remdesivir: The Adaptive COVID-19 Treatment Trial proved that remdesivir-treated patients had 31% faster time to recovery when compared to control
Case series and a small RCT suggested better outcomes with interferon and high-dose steroids in conjunction with supportive care.
References
1) Bitterman R, Kumar D. Respiratory Viruses in Solid Organ Transplant Recipients. Viruses. 2021 Oct 25;13(11):2146.
2) RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704.
3) Study of Scientific Board Republic of Turkey, Ministry of Health. COVID-19 (SARS-CoV-2 INFECTION) GUIDE. April 14th, 2020, Ankara, Turkey.
4)-Semenzato L, Botton J, Drouin J, et al. Chronic diseases, health conditions and risk of COVID-19-related hospitalization and in-hospital mortality during the first wave of the epidemic in France: a cohort study of 66 million people. The Lancet Glob Health Regional Health – Europe. 2021;
Management:
-Lab testing: CBC, ESR, D-DIMERS, LFTS, UECS, Sputum MCS/ZN staining, Ferritin, RBS, Amylase, Lipase ,D-Dimer
-If Covid 19 PCR +VE + URTI features ,we proceed for HRCT chest.
-An elderly patient, with kidney transplant & history of Wegner’s granulomatosis ;all predispose to severe infection, so this pt needs to be admitted for proper management.
-Resp support , IV dexamethasone.
– MMF discontinuation till COVID 19 PCR negative, at least 2 consecutive tests with improvement of symptoms.
-Decrease tac trough levels to 5-8ng/ml with stress doses of steroids.
– Remdesivir.
-DVT and Gastritis prophylaxis.
– Tocilizumab according to chest consultation.
-Monitoring of covidcomplications.;egAK,pancreatitis,MI,Arrythmias,coagulopathies ,vasculitis.
-Vaccination against COVID 19 following recovery.
References:
Saad I et al;COVID 19;breaking down a global health crisis ;Annals of clinical microbiology and antimicrobials;35(2021)
Halawa et al;Covid 19 in Kidney Transplant Recipients; Case series and brief review of current evidence .Nephron 2021;145(2);192-198
Hoeby P et al ;Recovery collaborative group; Dexamethasone in hospitalized pts with Covid 19.N Eng j med .2021 feb 25;384(8)693-704
Management
Kidney transplant recipient who tested positive for Sars-Cov2 RNA, CXR normal, kidney function stable and presented with a productive cough.
This patient will require admission for close observation and management, this is a 50 year old male kidney transplant recipient with history of wegners granulomatosis.
I will also order a HRCT for better characterisation of the lung involvement though the CXR is normal.
Other workups I will do in this patient will include:
D dimers, ferritin levels- this are acute inflammatory markers that are expected to be elevated in Covid 19. High levels have been associated with poor outcomes.
CRP and procalcitonin, sputum MCS/ZN staining, ESR- to rule out an infectious cause. High CRP levels have also been associated with poor outcomes in Ovid 19.
CBC- looking for lymphopenia
BGA, UECS,LFT
This patient currently is stable thus will first stop the MMF and reduce the tacrolimus trough levels to be between 8-12ng/ml. The use of antimetabolites in SOT with Covid 19 have been associated with poor outcomes CNI may be continued since they inhibit IL1 and 6.
Incase the patient desaturates or requires mechanical ventilation then there will be a role of switching the steroids to IV dexamethasone. Dexamethasone has been shown to reduce the 28 day mortality in hospitalised patients on mechanical ventilation or requiring oxygen supplementation.
Antivirals like remdesivir can also be given if the patient requires oxygen supplementation. Remdesivir was associated with better outcomes than controls.
Other medication that can be considered are baricitinib- for cases that steroids are contraindicated to be given with remdesivir, tocilizumab- in cases of cytokine storm.
What is the role of anticoagulation in the management of post-transplant covid infection?
Anticoagulants are indicated in moderate to severe cases of Covid 19 infections due to the thrombogenic activity of Sars-Cov2 hence increased risk of pulmonary embolism and thromboembolism.
For patients hospitalised and doesn’t need oxygen supplementation then the recommendation is to use prophylactic dose of heparin. However patients who require oxygen should be on therapeutic dose of heparin.
References.
Coronavirus Disease 2019 (COVID-19) Treatment Guidelines https://www.covid19treatmentguidelines.nih.gov/ on 3/26/2023
Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
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 a productive cough and 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
.How would you manage this case?
2.Substantiate your answer
Do other labs ;FHG, PCT, ESR, D-DIMERS, LFTS, UECS, BGA, Sputum MCS/ZN staining, Ferritin levels, RBS, Amylase, Lipase.
Covid 19 PCR +VE + URTI features would warrant a HRCT chest to get the severity of the lung involvement.
Elderly, post KTR with previous Wegner’s granulomatosis are all risk factors for a severe infection and for that reason this pt should be admitted in a healthcare facility for close monitoring.
Monitor resp status and initiate resp support in the event he starts desaturating. Initiate IV dexamethasone if in need of resp support to decrease inflammation and fasten recovery.
Stop MMF until COVID 19 PCR negative, at least x2 consecutive tests with resolution of presenting symptoms.
Decrease tac to 5-8ng/ml and give stress doses of steroids.
Initiate antivirals i.e remdesivir to decrease inflammation and shorten hospital stay.
DVT and Gastritis prophylaxis while in the ward.
Other consideration – Tocilizumab.
Monitor covid complications while in the ward ;AKI,Dysgycemia,Pancreatitis,MI,Arrythmias,vasculitis,Coagulopathies etc.
Covid 19 vaccination post recovery.
REF;
Saad I et al;COVID 19;breaking down a global health crisis;Annals of clinical microbiology and antimicrobials;35(2021)
Halawa et al;Covid 19 in Kidney Transplant Recipients; Case series and brief review of current evidence .Nephron 2021;145(2);192-198
Hoeby P et al ;Recovery collaborative group; Dexamethasone in hospitalized pts with Covid 19.N Eng j med .2021 feb 25;384(8)693-704
How would you manage this case?
this is covid pneumonia in immunocompromized patients above 50 years with AAV as a primary disease and on intense triple immunotherapy including MMF and tacrolimus with higher trough level
this patient needs hospital admission in an isolated room with close observation and asses for o2 requirements to send for inflammatory markers including CRP, FBC looking for lymphopenia, thrombocytopenia, LDH, DD test
HRCT may be considered if the patient became hypoxic to assess the level of lung involvement and rule out PE
start on consrevative medical therapy including hydration , heparin prophylaxis and if his CRP > 75 needs o2 therapy will consider dexamethasone 6 mg along with remidasevir for 5 -10 days
hold MMF and continue on tacrolimus adjusted dose along with perdnisolone
A normal CXR does not exclude lung involvement in COVID A HRCT chest should be considered along with Ferritin LDH As patient has productive cough and he is highly immunosuppressed with a possibility of worsening of clinical condition. In such scenario HOSPITAL ADMISSION is a better option
If HRCT chest confirms lung involvement
Remdesivir should be administered
Dexa should be reserved for oxygen dependent patients
All patients admitted to hospital should be given LMWH after careful assessment
⭐ Case with COVID infection:
_Isolation to protect against spread of infection, health care providers must use appropriate PPE.
_Ensure good hydration , use of supportive therapy (antipyretics, IV fluids and oxygen therapy as needed).
_stop antiproliferative (MMF and AZA).
_in severe cases:
👉 Consider stoppage of CNI.
👉 consider high dose dexamethasone in suspected cytokine storm (6 mg/day) and assisted ventilation either CPAP or entubation and MV.
👉 consider antiviral as (remdisivir) to improve survival and rapid recovery.
_ add anticoagulant prophylactic dose to prevent thrombosis.
_Follow up serum LDH, ferritin, D dimer, CRP.
_follow up liver and kidney functions.
_Close monitoring of graft function.
A KTR with uncomplicated COVID-19 infection in the early post-transplant period. He is vitally stable with clear CXR and stable KFT.
1. I will admit this patient aiming at isolation in the hospital beside supportive measures and close observation to guard against anticipated complications in COVID-19 infection.
2. I will adjust the dose of TAC to be in the range of 4-6ng/ml. I will reduce the ant-metabolite dose(MMF) by 50%. I will keep him on prednisolone.
3. Required laboratory work-up in COVID-19 infection(1):
· 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.
4. Considering the outcome of the recovery trial is helpful in guiding the management plan of this patient(2): a) Aspirin was added to the trial because it is used to prevent blood clots, patients with COVID-19 are at higher risk of blood clots forming in their blood vessels. It is also cheap and widely available, which make it a good candidate. b) Tocilizumab reduces deaths in patients hospitalized with COVID-19.The study also showed that tocilizumab shortens the time taken for patients to be successfully discharged from hospital, and reduces the need for a mechanical ventilator. c) Baricitinib reduces deaths in hospitalized patients.The RECOVERY team found that treatment with baricitinib reduced deaths by 13%. It also reduced the chance of progressing to invasive mechanical ventilation. d) 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. Dexamethasone reduces deaths by up to one third.
References 1. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current EvidenceMuhammed Ahmed Elhadedy, Yazin Marie, Ahmed HalawaNephron 2021;145:192–198 DOI: 10.1159/000512329
Patients with COVID-19 are at higher risk of blood clots forming in their blood vessels. Aspirin was added to the recovery trial trial because it is used to prevent blood clots, . it is also cheap and widely available, which make it a good candidate.
isolation, either home isolation or in-ward isolation. non-transplant patient may undergo home isolation when being stable and no need for supportive oxygen therapy. SOT recipient will benefit more from isolation at hospital base to guard against anticipated complications of COVID-19 infection.
American society of hematology 2021 guidelines advised (based on low quality evidence) the use of of prophylactic-intensity anti-coagulation for COIVD-19 related critical illness for those who do not have confirmed or suspected VTE
Role of anticoagulants in Post-transplant COVID infection.
In outdoor patients
if there is risk of possible ischemia or infraction like PE, DVT etc than consider LMWH or unfractionated heparin in patients with GFR < 15ml/min, fondaparinux can be used in patient who has Hx of HIT.
In patients who are already on anticoagulants eg for AF or VTE better to continue previous anticoagulants or to switch to short acting agents in case of admission to hospital for COVID-19 infection.
In case of warranted admission to hospital for covid infection
if admitted to ICU/HDU LMWH if preferred switch to unfractionated heparin in case of GFR <15 ml/mi. use fondaparinux if history of HIT.
Use for upto 3 months for covid infection related complication like VET or continue if covid unrelated indication like AF, VET that is deemed to require indefinite anticoagulation
⭐COVID 19 is well known to have thrombogenic activity, hence use of prophylactic anticoagulant is warranted especially in high risk groups (elderly, use of steroids or oral contraceptive therapy, hospitalized patients with severe infection), so it is indicated here.
.🎯 As regard hospitalization:
_indicated for severe cases with hypoxemia (requiring oxygen therapy or assisted ventilation).
_high risk patient as transplant recipient.
_patient with multi system affection or cytokines storm.
What is the role of anticoagulation in the management of post-transplant COVID infection?
Anticoagulation has been recommended in moderate to severe, and critically ill COVID-19 patients, as in any acutely ill, hospitalized patient (1). This is especially important in the context of COVID-19 being associated with coagulation dysfunction and consequent venous thromboembolism and pulmonary embolism. As per the British Transplantations society, all patients admitted for COVID-19 should be assessed for thromboprophylaxis, and majority would require it. Therapeutic low molecular weight heparin (LMWH) should be used for patients requiring supplemental oxygenation. Lower doses should be used in critical patients (on high-flow oxygen, CPAP, NIV or invasive ventilation) without any indication of therapeutic anticoagulation (2).
What about hospitalisation?
The indications for hospitalization in a COVID-19 patient include (3):
1. A room air oxygen saturation of <94%
2. Respiratory rate of >30.
3. PaO2/FiO2 <300 mmHg
4. Lung infiltrates >50%
References:
Chandra A, Chakraborty U, Ghosh S, Dasgupta S. Anticoagulation in COVID-19: current concepts and controversies. Postgrad Med J. 2022 May;98(1159):395-402. doi: 10.1136/postgradmedj-2021-139923. Epub 2021 Apr 13. PMID: 33850011.
Covid 19 tx guidelines panel recommendations – Last updated Dec 1 2022.
Those receiving anticoagulation or antiplatelet for underlying conditions to continue unless bleeding develops or they get other CI.
In absence of imaging, those with high risk for thrombosis to be anti coagulated.
Those who need ECMO or CRRT to be anticoagulated like those without covid 19.
Non hospitalized not to get anticoagulation or antiplatelet for prophylaxis unless participating in a clinical trial.
No role for continuous VTE prophylaxis post discharge unless otherwise indicated or pt has enrolled in a clinical trial.
Therapeutic doses of heparin to be given in pts with high DDIMERS on low flow/high flow oxygen oxygen without risk of hemorrhage for 14 days or until moved to ICU or discharged home.
REF ;
NIH;COVID 19 treatment guidelines, last updated Dec 1 2022.
– development of thrombosis during hospitalisation was a unique feature in Covid-19 patients compared with other viral infections
– individualise treatment, weigh risk vs benefit when deciding on the dose
– prophylactic dosing is preferred for ICU patients
– therapeutic dosing is preferred for non-ICU inpatients
– adjust dose according to weight and kidney function
– LMWH is generally preferred over other anticoagulants
– thromboprophylaxis is usually stopped at discharge
– no need for thromboprophylaxis for outpatients
– initiate therapeutic dose anticoagulation for documented VTE or high suspicion for VTE, continue for at least 3 months
– UFH is preferred for unstable patients with organ dysfunction
– LMWH or DOACs can be used in stable patients without organ dysfunction
References
1. Schulman S, Sholzberg M, Spyropoulos AC, Zarychanski R, Resnick HE, Bradbury CA, et al. ISTH guidelines for antithrombotic treatment in COVID-19. Journal of thrombosis and haemostasis : JTH. 2022 Oct;20(10):2214-25. PubMed PMID: 35906716. Pubmed Central PMCID: PMC9349907. Epub 2022/07/30. eng.
2. Cuker A, Tseng EK, Schünemann HJ, Angchaisuksiri P, Blair C, Dane K, et al. American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis for patients with COVID-19: March 2022 update on the use of anticoagulation in critically ill patients. Blood advances. 2022 Sep 13;6(17):4975-82. PubMed PMID: 35748885. Pubmed Central PMCID: PMC9236618. Epub 2022/06/25. eng.
COVID 19 is well known to have thrombogenic activity, hence use of prophylactic anticoagulant is warranted especially in high risk groups (elderly, use of steroids or oral contraceptive therapy, hospitalized patients with severe infection), so it is indicated here. As regard hospitalization: _indicated for severe cases with hypoxemia (requiring oxygen therapy or assisted ventilation). _high risk patient as transplant recipient. _patient with multi system affection or cytokines storm.
Q1: in case of hospitalization like this case, prophylactic anticoagulation with LMWH is recommended. Q2: hospitalization is necessary for high-risk cases like our patient and O2 sat<= 93%, RR>30, and more than 50% lung involvement.
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 a productive cough and 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.
How would you manage this case?
After full history and examination with evaluation of the volume status of the patient.
Even with a normal CXR – I will order a HRCT of the chest for better classification of lung involvement.
I will admit this patient to hospital in an isolation roam, as considered high risk patient-( 50 yrs + kidney transplant + h/o ANCA vasculitis).
Laboratory: Full blood count(CBC), urinalysis, CRP, ESR, Kidney function test- creatinine, BUN, Na,k, Liver function test-AST, ALT, bilirubins, albumin, INR, LDH, ferritin, and D-dimer, Blood, urine and throat swab culture.
Frequent monitoring of his respiratory rate and O2 saturation, O2 therapy by nasal cannula, if mild or by high flow oxygen when needed or even non invasive ventilation securing the oxygenation.
I would stop MMF for few days till two swabs Negative for COVID, and clinical improvement.
Reduce the dose of tacrolimus to the lower therapeutic level of 4 ng/dl, and give a stress dose steroid.
Early start of viral RNA inhibitor (remdesivir) reduce viral load and time in hospitals, and reduce the risk of having a cytokine storm.
IV hydration, anticoagulation (DVT prophylaxis), PPi (GI prophylaxis).
IV antibiotics ex. Ceftriaxone.
In case of cytokine storm (high persistent fever, CRP,D-dimer, hypofibrinogenemia , high ferritin) –early start of dexamethasone 6 mg daily for 10 days may reduce 28 days mortality, and Tocilizumab may enhance survival in such patients.
References
(1) Danziger-Isakov L, Blumberg EA, Manuel O, Sester M. Impact of COVID-19 in solid organ transplant recipients. Am J Transplant. 2021 Mar;21(3):925-937. doi: 10.1111/ajt.16449. Epub 2021 Feb 26. PMID: 33319449; PMCID: PMC9800718. (2) Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980. (3) RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595. (4) Belsky JA, Tullius BP, Lamb MG, Sayegh R, Stanek JR, Auletta JJ. COVID-19 in immunocompromised patients: A systematic review of cancer, hematopoietic cell and solid organ transplant patients. J Infect. 2021 Mar;82(3):329-338. doi: 10.1016/j.jinf.2021.01.022. Epub 2021 Feb 4. PMID: 33549624; PMCID: PMC7859698.
Management of Covid-19 infection in kidney transplant recipients
Supportive management (IV fluid and keep saturation > 95%)
Stop MMF.
Reduce TAC by 50% (monitor drug level with target TAC level 3-4) and return back to immunosuppressants regimen as early as the infection is cured to avoid allograft dysfunction)
A short course of dexamethasone, 6 mg OD for up to 10 days (improved survival especially in MV patients).
Tocilizumab and baricitinib in combination with dexamethasone if the condition deteriorates.
Anticoagulation, unless platelets <50,000.
Antiviral
a) Paxlovid oral if the condition is mild without respiratory compromisation. b) Remdisivir IV for 3 consecutive days if the condition deteriorates. References
Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403-416. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33378609.
Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N Engl J Med. 2020;383(27):2603-2615. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33301246.
Boyarsky BJ, Werbel WA, Avery RK, et al. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. JAMA. 2021;325(21):2204-2206. Available at:
Supportive management (IV fluid and keep saturation > 95%)
Stop MMF.
Reduce TAC by 50% (monitor drug level with target TAC level 3-4) and return back to immunosuppressants regimen as early as the infection is cured to avoid allograft dysfunction)
A short course of dexamethasone, 6 mg OD for up to 10 days (improved survival especially in MV patients).
Tocilizumab and baricitinib in combination with dexamethasone if the condition deteriorates.
Anticoagulation, unless platelets <50,000.
Antiviral
a) Paxlovid oral if the condition is mild without respiratory compromisation. b) Remdisivir IV for 3 consecutive days if the condition deteriorates. References
Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med. 2021;384(5):403-416. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33378609.
Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA COVID-19 vaccine. N Engl J Med. 2020;383(27):2603-2615. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33301246.
Boyarsky BJ, Werbel WA, Avery RK, et al. Antibody response to 2-dose SARS-CoV-2 mRNA vaccine series in solid organ transplant recipients. JAMA. 2021;325(21):2204-2206. Available at:
Wegener’s granulomatosis can be triggered by covid or any other infection. For that reason, I will admit this patient because the right perihilar area seems infiltrated (?!). The picture can be better evaluated with CT though not very necessary as long as the patient doesn’t have dyspnea or abnormal oxygenation. I will follow up the CBC, CRP, D-dimer, LSH and other biochemistry.
I will stop MMF and give either 8 mg dexamethasone or 40 mg prednisolone. TAC level is above the target; lowering the dose somehow with a follow-up of renal function is needed.
At that time, we did not have plenty of medications but Favipravir so that we could start it despite its controversy. Remedisivir is an option where available.
Monitoring of renal function and respiratory symptoms
supportive inhaler therapy and oxygen when needed
In the above case,patient has mild symptoms and COVID 19 test positive so to assess for severity-few tests like complete blood picture, renal and liver function tests ,D-Dimers ,inflammatory markers like CRP, serum ferritin, LDH, HRCT chest should be done .Treatment will depend on the severity of Covid.The above patient falls into mild category so should be managed as an outpatient case -just withholding MMF and reduction of Tacrolimus to 5-7ng/ml with supportive treatment for fever ,diarrhea and close monitoing of graft function. Counseling should be done that f condition deteriorates –ten immediately report to hospital for admission.
Hospitalized patients with mild-moderate patients will be managed with anti-coagulation along with supportive management –they may need dexamethasone up to 6 mg which may hasten recovery(RECOVERY TRIAL)For severe cases-Drugs which can be tried include Tocilizumab ,baricitinib ,Favipiravir, Molnupiravir, Nimatrelvir/ritonavir but have to be cautious about drug-drug interaction.
REFERENCES:
1- Banerjee D., Popoola J., Shah S., Ster I., Quan V., et al. COVID-19 infection in kidney transplant recipients.Kidney Int., 2020;97(6):1076-1082
2- RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, Mafham M, Bell JL,et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704.
This is a confirmed case of COVID 19 infection with mild symptoms. There are good renal functions. This case can be managed as outpatients. However he will be warned of clinical signs of deterioration . In that case he will require hospital admission. These signs are persistent fever and drop in oxygen saturation. AS he is on immune suppression and hospital admission can also be considered for better monitoring.
Patient will be advised for good hydration
Watching oxygen saturations and give oxygen if it is < 90%
HRCT Chets
Stop MMF and continue CNI
Watch TAC levels with target upto 4-6 ng/ml
Dexamethasone upto 6 mg OD
Inhalational steroids can be considered if saturation drops
Watching blood glucose and graft functions
Those at high risk of progression can have Remdesivir for 3 days
Watching for D Dimers and start anti coagulation if necessary,
Chloroquine and HCQ have been reported to have antiviral activity, to inhibit cytokine production, and to be associated with improved CT pulmonary images, a rapid decline in fever, and a quicker recovery period. The effect seems to be reinforced by azithromycin
Follow up is necessary to assess respiratory functions
COVID 19 immunization later
Nair V, Jandovitz N, Hirsch JS, Nair G, Abate M, Bhaskaran M, Grodstein E, Berlinrut I, Hirschwerk D, Cohen SL, Davidson KW, Dominello AJ, Osorio GA, Richardson S, Teperman LW, Molmenti EP. COVID-19 in kidney transplant recipients. Am J Transplant. 2020 Jul;20(7):1819-1825
Yes, as you suggest, I agree that you would consider stopping MMF for few days. However, I do NOT agree with your suggestion: hydroxychloroquine/chloroquine, azithromycin.
Please read my comment in the thread of second article of journal club in week 9 ridiculing a number of unproven treatments that have been suggested, when I wrote a short story of a dog believing its barking would trigger train to leave the station!
Typing whole sentence in bold or typing in capitals amounts to shouting.
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 a productive cough and 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.
How would you manage this case?
A case of post Kidney transplant with SARS-COV-2 RNA positive and productive cough with history of Wegner’s granulomatosis. 1st: In Our Center I will admit any immunocompromised patient for close observation (ABG/O2Sat) and more workup (CT chest, Transplant ID opinion to start Remdesivir or not). In General we can treat with supportive treatment (good hydration and acetaminophen as needed)) and treated as outpatient with close fu (O2Sat at home )monitoring and no need for hospitalization see next=> We should classify our patient according to the clinical manifestation:
1-Asymptomatic patientsand patients with mild disease (oxygen saturation above 93%, no lung involvement on chest computed tomography) were followed up in the outpatient clinic weekly. 2-Patients with moderate disease(oxygen saturation above 90%, respiratory rate under 30 breaths/min) were hospitalized in the first wave of the pandemic and followed up in the outpatient clinic in the later period because of hospital overcrowding. 3-Hospitalization were severe disease(oxygen saturation under 90%, respiratory rate above 30 breaths/min), cytokine storm (persistent fever, high or increasing CRP, ferritin, and D-dimer, abnormalities in liver function tests, hypofibrinogenemia with cytopenia in the forms of lymphopenia and thrombocytopenia). High Risk Patient (Severity & Mortality) Factors: Age > 55 years Numerous pre-existing comorbidities Hypoxia CT showing extensive lung involvement. Various laboratory test abnormalities Biomarkers of end-organ dysfunction.
How would you manage this case? Detailed history and comprehensive clinical examination Any history of contact with SARS2-CoV positive patients. ABCD, ABG, O2 Saturation and D-Dimer CT thorax without iv contrast to DD Hge from infection CBC, (lymphopenia may be seen) Kidney function tests. Urine Analysis, Urine and Blood C/S CNIs level TB (Mantoux, IGRA, and sputum culture) Screening
Fungal (PJP) (induced sputum or bronchoscopy for BAL) screening Sr. Ferritin, IL-6. CMV viral load. LDH, Ferritin, CRP and procalcitonin Management:
Admission in isolation room, under observation (ABG/ O2Sat)
Supportive medical therapy,good hydration (IV fluids and acetaminophen as needed). Reduction of immunosuppressive medications or even discontinued. Discontinued MMFor decrease 50% and continue CNIswith close graft monitoring the patient (immunosuppression treatment should be individualized based on the careful assessment of each patient) Tacrolimus Trough levelswere adjusted as 4–6 ng/dL. Drugs targeting immune response regulation: Interferons And Dexamethasone. Dexamethasone in those receiving respiratory support (invasive mechanical ventilation or oxygen alone): resulted in lower 28-day mortality (3) Drugs that preventing viral replicatation: Paxlovid, remdesivir, molnupiravir, favipiravir, ribavirin, & Kaletra.
Remdesivir:The Adaptive COVID-19 Treatment Trial proved that remdesivir-treated patients had 31% faster time to recovery when compared to control (1) Case series and a small RCT suggested better outcomes with interferon and high-dose steroids in conjunction with supportive care (2) References 1) Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
2)Bitterman R, Kumar D. Respiratory Viruses in Solid Organ Transplant Recipients. Viruses. 2021 Oct 25;13(11):2146. doi: 10.3390/v13112146. PMID: 34834953; PMCID: PMC8622983.
3)RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595. 4)Samavat et al. COVID-19 in Kidney Transplantation Recipients, Iranian Journal of Kidney Diseases | Volume 14 | Number 3 | May 2020
5-Demir, E., Ucar, Z.A., Dheir, H. et al. COVID-19 in Kidney Transplant Recipients: A Multicenter Experience from the First Two Waves of Pandemic. BMC Nephrol 23, 183 (2022). https://doi.org/10.1186/s12882-022-02784-w.
6-Study of Scientific Board Republic of Turkey, Ministry of Health. COVID-19 (SARS-CoV-2 INFECTION) GUIDE. April 14th, 2020, Ankara, Turkey.
7-Semenzato L, Botton J, Drouin J, et al. Chronic diseases, health conditions and risk of COVID-19-related hospitalization and in-hospital mortality during the first wave of the epidemic in France: a cohort study of 66 million people. The Lancet Glob Health Regional Health – Europe. 2021; 8:100158. https://doi.org/10.1016/j.lanepe.2021.100158.
This patient is 2 months post transplant and is on triple immunosuppression after receiving a kidney from a living donor. He has a history of Wegners granulomatosis
He has COVID 19 disease as evidenced by a positive PCR after having a productive cough
Based on his signs and symptoms, he has has mild COVID 19 disease as his vital signs are stable and his CXR is clear
He is in the early post-transplant phase
We should get more history to assess his rejection risk:
The HLA mismatch and which class mismatch
The DSAs
This is important as this will guide further treatment
The ideal treatment in patients who develop moderate to severe COVID 19 disease post transplant is to reduce the immunosuppression and to stop the antimetabolite and to continue with the CNI as the CNIs inhibit IL1 and IL6. This is always weighed against the risk of the patient developing acute rejection.
The use of antimetabolites in COVID 19 has been linked to poor outcomes in SOT recipients. However, whether stopping the antimetabolites during the COVID 19 infection improved outcomes remains unclear
Some authors have postulated that maintenance of immunosuppression will dampen the inflammatory cytokine storm seen in COVID 19 infections.
There was a reported higher risk of bacterial and fungal infections after using therapies for COVID 19 including dexamethasone and IL 6 inhibitors
The SOT patients who have COVID 19 infection are known to shed the virus longer than the general population. Therefore, these patients need to be careful after contracting COVID 19 as the risk of transmission remains higher even after 21 days. There is also a higher risk of relapse
For this patient, I would reduce the tacrolimus levels to between 8-12, maintain supportive care and manage the patient as an outpatient, and closely monitor the patient for developing acute rejection or progressing to develop severe disease
An Overview of COVID 19 in Solid Organ Transplantation. L. Bartelt, D. van Duin / Clinical Microbiology and Infection 28 (2022) 779e784
Your reply is rather limited. It does not address all the concerns. I like that you would effect the following modification in immunosuppression: reduction of tacrolimus and stopping MMF for few days.
Typing whole sentence in bold or typing in capitals amounts to shouting.
This patient is known case of wegener granulomatosis present 2 month after kidney transplantation with productive cough which was tested positive for SARS-COV- 2 RNA with normal clinical examination and stable graft function ,his prograf level is 13.4ng/ml
Management of COVID-19 ;
This patient has mild covid 19 infection depending on the above mentioned data so no need for hospital admission. He needs a full blood count looking for lymphopenia,inflammatory markers ,graft functions .Home management with self isolation Adjustment of tacrolimus dose to therapeutic level MMF dose can be reduced to 250 mg bid and to be stopped if the patient is deteriorating .Advice the patient to follow oxygen saturation at home and to come immediately if desaturated or developed shortness of breath .
References;
Demir, E., Ucar, Z.A., Dheir, H. et al. COVID-19 in Kidney Transplant Recipients: A Multicenter Experience from the First Two Waves of Pandemic. BMC Nephrol 23, 183
Your reply is rather limited. It does not address all the concerns. I like that you would effect the following modification in immunosuppression: reduction of tacrolimus and stopping MMF for few days.
The index patient is a recent (2 month back) live donor renal transplant recipient with basic disease of granulomatous polyangiitis, on tacrolimus based triple drug immunosuppression, presenting with productive cough. Clinical examination is unremarkable, and SARS-CoV-2 test is positive.
The management of the index case involves:
A detailed clinical examination: Respiratory system examination, especially looking for tachypnea. SpO2 should be checked to assess hypoxia.
Laboratory testing including complete blood count (especially look for lymphopenia), renal function tests, liver function tests, C reactive protein, blood culture, chest X ray, Tacrolimus trough levels, LDH, ferritin and Interleukin-6 (IL-6).
High resolution computed tomogram (HRCT) of chest for risk stratification (1,2).
Initial treatment (3):
a. Isolation of the patient.
b. In case there is no hypoxia and only cough without any tachypnea, patient can be isolated at home. Monitoring of temperature, respiratory rate and SpO2 can be done at home and the patient can remain in contact with the clinician via tele-medicine.
c. Mild to moderate illness (SpO2 >94% without requiring any supplemental oxygen) does not require anything other than symptomatic treatment (3). Those with high risk of progression (obesity, diabetes mellitus, hypertension, immunosuppressed patients) may be given high-titre COVID-19 convalescent plasma if within 8 days of onset of disease. Other options include 3 days of remdesivir (within 7 days of symptom onset), nirmatrelvir/ritonavir or molnupiravir (within 5 days of onset), or neutralizing monoclonal antibodies (within 7 days of onset). No role of hydroxychloroquine, azithromycin, lopinavir/ritonavir, dexamethasone, inhaled steroids, dexamethasone ivermectin, colchicine, and famotidine in such patients.
d. If the patient worsens and develops severe (SpO2 <94% on room air) or critical (end-organ dysfunction, requiring ventilatory support) illness, patient should be admitted in hospital. Dexamethasone 6 mg daily for 10 days should be given. 5 days of remdesivir treatment can be given to patients on supplemental oxygen (but not to patients on mechanical ventilation). Those who cannot be given steroids due to contraindication, should be given Baricitinib with remdesivir. In presence of elevated markers of systemic inflammation, use of Tocilizumab (or Sarilumab) is recommended (3).
e. Immunosuppression: In the index patient, MMF can be reduced to 250 mg twice a day. Antimetabolites should be stopped and tacrolimus doses to be adjusted as per trough (target 4-6) levels in case of severe or critical illness (3). We should be watchful for worsening of graft function/ rejection due to reduction in immunosuppression.
Substantiate your answer
The index patient is having a mild to moderate COVID-19 disease (only symptom is productive cough, unremarkable clinical examination, clear chest x ray and stable graft function). He should be managed as outpatient, be kept in home isolation, managed symptomatically, with close self-monitoring via tele-consultation. In case of worsening symptoms, or fall in SpO2, patient should be hospitalized and managed with remdesivir for 3 days (200 mg on first day and then 100 mg daily) or for 5 days (if supplemental oxygen is required but not on ventilator or ECMO). MMF should be stopped and tacrolimus dose should be adjusted with target trough level of 6. If oxygen saturation falls to <94%, dexamethasone 6 mg daily for 10 days should also be started (4). Further worsening would require Tocilizumab (in presence of elevated inflammatory markers like IL-6). Due to early post-transplant period (2 months old), the risk of acute rejection should be kept in mind.
References:
Jayachandran AK, Nelson V, Shajahan ME. Chest CT severity score as a predictor of mortality and short-term prognosis in COVID-19. J Family Med Prim Care. 2022 Aug;11(8):4363-4367. doi: 10.4103/jfmpc.jfmpc_209_22. Epub 2022 Aug 30. PMID: 36353028; PMCID: PMC9638539.
Saeed GA, Gaba W, Shah A, Al Helali AA, Raidullah E, Al Ali AB, Elghazali M, Ahmed DY, Al Kaabi SG, Almazrouei S. Correlation between Chest CT Severity Scores and the Clinical Parameters of Adult Patients with COVID-19 Pneumonia. Radiol Res Pract. 2021 Jan 6;2021:6697677. doi: 10.1155/2021/6697677. PMID: 33505722; PMCID: PMC7801942.
Bhimraj A, Morgan RL, Shumaker AH, Baden L, Cheng VCC, Edwards KM, Gallagher JC, Gandhi RT, Muller WJ, Nakamura MM, O’Horo JC, Shafer RW, Shoham S, Murad MH, Mustafa RA, Sultan S, Falck-Ytter Y. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. Clin Infect Dis. 2022 Sep 5:ciac724. doi: 10.1093/cid/ciac724. Epub ahead of print. PMID: 36063397; PMCID: PMC9494372.
RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
A case of renal transplant recipient from a living donor on triple maintenance therapy with stable kidney function ,he was a known as a case of Wegner granulomatosis presented 2 months post transplant with SARS COV 2 infection.
Management
The patient need to be evaluated regarding detailed medical history, his clinical exam is unremarkable .
His oxygen saturation and general condition need assessment to decide if he needs admission or home isolation with close follow up can be suitable
Investigations
include full basic lab as CBC with differential ,KFT ,LFT ,electrolytes ,urine analysis and culture ,sputum and blood culture , inflammatory markers as ferritin ,LDH and ddimer, crp ,Tac trough level,coagulation profile
Treatment
Isolation along with supportive care in the forum of good hydration and antipyretics if needed along with symptomatic treatment
US FDA authorized remdesivir administration as a treatment option for hospitalized COVID-19 patients given 200 mg intravenously on the first day followed by 100 mg intravenously daily.
If he deteriorated became oxygen dependent dexamethasone 6 mg can be added
The Recovery Collaborative Group has shown that dexamethasone benefits hospitalized patients receiving oxygen therapy
For immunosuppression as the graft function is stable ,MMF can be suspended and tacrolimus can be continued with reducing the dose and monitoring of trough levels to prevent allograft rejection and CNI toxicity
If patient deteriorated with cytokine storm signs Toclizumab 400 mg IV once
Reference
– Elhadedya M A , Mariea Y ,Halawa A .COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence.Nephron 2021;145:192–198
-Ravi Raju Tatapudi, Venkateswara Rao Kopparti, Anusha Poosapati, Srinivas Metta, Atchyutha Rao Gongada, Balakrishna Vedulla, “SARS-CoV-2 Infection in Kidney Transplant Recipients: A Single-Centre Study of 20 Cases from India”, International Journal of Nephrology, vol. 2021, Article ID 2243095, 7 pages, 2021.
I like your clinical approach. I like the following modification in immunosuppression: reduction of tacrolimus and stopping MMF for few days. I am not sure if this patient would really need anti-COVID drug.
– The index case 2 months post-KT, confirmed to have COVID-19 infection, and mild clinical presentation.
– This patient can be managed at home to reduce the risk of acquiring nosocomial infection.
– At any point if symptoms progress, consider admission.
– Need to ensure easy hospital access and communication with transplant center, otherwise, will be managed as inpatient.
– Ensure normal O2 saturation.
Work up:
– CBC; VBG, CRP, ESR, ferritin, coagulation profile.
– LFT and Kidney function test.
– Tacrolimus level monitoring.
Treatment;
– Supportive management; ensure good hydration, control fever if present.
– Management of immunosuppressive is challenge need to balance with rejection risk.
– Hold antimetabolite, especially in lymphopenic patients (absolute lymphocyte count <700 cells/mL)
– CNI inhibit IL-1 and IL-6 which contribute to the severity of covid infection.
– However, the level is 13 high need to be reduced to 8-10.
– If infection is sever and progressive we can reduce CNI through level or complete stopping while increasing steroids does.
– Monitor graft function closely.
– Dexamethasone if patient require respiratory support, reduce mortality.
– All antiviral therapy are investigational, Not required in our index case.
– Consider drug-drug interaction if any new treatment used.
* Remdesivir; can be used if duration of symptoms < 7 days, RCT showed 87% reduction in risk of hospitalization or death among high-risk, non-hospitalized patients who received a 3-day course of remdesivir compared to those who received the placebo.
*Nirmatrelvir-ritonavir; for emergency use in mild to moderate symptomatic COVID-19 in patients at high risk for progression,
-Advice on COVID-19 vaccination after recovery from acute infection References:
Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
Bitterman R, Kumar D. Respiratory Viruses in Solid Organ Transplant Recipients. Viruses. 2021 Oct 25;13(11):2146. doi: 10.3390/v13112146. PMID: 34834953; PMCID: PMC8622983.
RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
Brady, D.K., Gurijala, A.R., Huang, L., Hussain, A.A., Lingan, A.L., Pembridge, O.G., Ratangee, B.A., Sealy, T.T., Vallone, K.T. and Clements, T.P. (2022), A guide to COVID-19 antiviral therapeutics: a summary and perspective of the antiviral weapons against SARS-CoV-2 infection. FEBS J. https://doi.org/10.1111/febs.16662
Gottlieb RL, Vaca CE, Paredes R, Mera J, Webb BJ, Perez G, Oguchi G, Ryan P, Nielsen BU, Brown M, Hidalgo A, Sachdeva Y, Mittal S, Osiyemi O, Skarbinski J, Juneja K, Hyland RH, Osinusi A, Chen S, Camus G, Abdelghany M, Davies S, Behenna-Renton N, Duff F, Marty FM, Katz MJ, Ginde AA, Brown SM, Schiffer JT, Hill JA; GS-US-540-9012 (PINETREE) Investigators. Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients. N Engl J Med. 2022 Jan 27;386(4):305-315. doi: 10.1056/NEJMoa2116846. Epub 2021 Dec 22. PMID: 34937145; PMCID: PMC8757570.
I like your well-referenced clinical approach. I like the following modification in immunosuppression: reduction of tacrolimus and stopping MMF for few days.
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 a productive cough and 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.
==================================================================== How would you manage this case?
History
Wegner’s granulomatosis
kidney transplant in February 2020
on April 3 presented with a productive cough and tested positive for SARS-CoV-2 RNA despite unremarkable clinical examination.
The chest X-ray was clear, and kidney function tests were stable.
Tacrolimus (trough level was 13.4 ng/mL).
Tacrolimus goals and achieved levels (average trough level) at months 1, 4, and 12.
Elhadedy, Muhammed Ahmed et al. “COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence.” Nephron vol. 145,2 (2021): 192-198. doi:10.1159/000512329
I like the following modification in immunosuppression: reduction of tacrolimus and stopping MMF for few days. Typing whole sentence in bold or typing in capitals amounts to shouting.
In general, Transplant patients are at a high risk of infection due to multiple risk factors, including immunosuppression, underlying CKD, and associated comorbidities including HTN and DM. Some studies reported that hypertensive and diabetic patients have a double-fold risk of infection, while COPD patients have a 5-fold risk.In view of COVID 19 era,transplant patients needs a special care if they are infected.
In ur case scenario of stable transplant patient with stable graft function with mild COVID infection .He has history of vasculitis which can be considered as a risk factor ,the management will be as following:
-Isolation
-Plenty amount of fluids
-Symptomatic treatment of fever if there.
-oral antibiotics to guard against secondary bacterial infections
-Daily CBC,renal function,CRP,procalcitonin,ferritin level and ABGs.some studies showed low lymphocyte/white blood cell ratio both on admission and during hospitalization had fatal outcomes.
-Repeat chest x ray(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).
-Immunosuppression: Hold MMF,switch oral steroids to IV steroids ,reduce tacrolimus dose in settings of high trough level targeting 5-8 ng/ml. Managing immunosuppression in kidney transplant recipients depends on the age, the severity of infection, the post-transplant duration, any other associated comorbidity, tissue mismatch, and any episodes of rejection should be considered in hold or reduce the immunosuppression and the treatment should be individualized based on the careful assessment of each patient.
-Close monitoring of oxygen saturation ,UOP and hemodynamics.
-From experience of COVID patients they have unpredictable curse.
The recent studies after COVID era 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.
References:
1- Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020 May;97(5):829–38
2- Chu KH, Tsang WK, Tang CS, Lam MF, Lai FM, To KF, et al. Acute renal impairment in coronavirus-associated severe acute respiratory syndrome. Kidney Int. 2005 Feb;67(2): 698–705
Immunosuppression is one of many risk factors that puts transplant recipients at a greater risk of infection. MANAGMENT
Daily differential complete blood count (CBC) with an emphasis on the total lymphocyte count trend
Basic metabolic panel
Hepatic panel
C-reactive protein (CRP)
Lactate dehydrogenase
Prothrombin time (PT)/partial thromboplastin time (PTT)/fibrinogen/D-dimer
measure O2 saturation Features suggest a severe illness:
Hyperoxia (oxygen saturation of less than 94% in room air)
Requirement for ventilator support or oxygenation FURTHER MANAGMENT
Level of TAC. Need to be recheck and need to be adjust accordingly, it seems to be high as patient might be on antiviral drugs,
Graft function monitoring and may require graft biopsy to check rejection.
Only moderate to severe cases call for reducing immunosuppression.
Given that the patient’s symptoms are not severe, there is no need to increase the steroid dosage for the existing patients.
If the following criteria are met, specific antiviral medication (oral nimatrelvir/ritonavir or intravenous remdisvir) is appropriate in mild to moderate cases.
1-Patients run the danger of their illness progressing to a severe stage, including;
patients with compromised immunity (SOT, HIV)
Individuals with various comorbid conditions, such as cancer, diabetes mellitus (DM), smoking, , tuberculosis (TB), cerebrovascular illness,
Patients over the age of 65 Patients
2-Patients who are more than 7 days past the onset are only treated with supportive measures. The duration from symptom onset is 5 days for nimatrelvir/ritonavir and 7 days for remdisvir.
Tacrolimus dose reduction because the trough level is already high, begin antiviral medication that may raise CNI levels even further, and monitor those levels.
I like your clinical approach. I like the following modification in immunosuppression: reduction of tacrolimus. But you have not mentioned stopping MMF for few days. I am not sure if this patient would really need anti-COVID drug.
The management of Covid-19 in post renal transplantation nearly same as general population despite some differences such as higher rate of hospitalization, AKI
, longer viral shedding but mortality nearly same
this case scenario….mild and patient in very critical early post operative period, so require close monitoring
investigations as other Covid-19 cases as per centers
Treatment as per local Covid-19 centers; in mild cases supportive treatment
adjustment of drugs and stop antimetabolite medications
Your reply is rather limited. It does not address all the concerns. I like to believe that you would effect the following modification in immunosuppression: reduction of tacrolimus and stopping MMF for few days.
– I will measure O2 saturation (O2 sat ≤ 92% is considered severe) and perform Borg scale after 6 minutes exercise to better asses the severity of dyspnea and the patient will inform us about the severity of dyspnea (mild, moderate or severe)
– CT is not indicated once the patient ha mild symptoms with normal O2 saturation and normal CXR imaging
– Reduction of immunosuppression is indicated only in moderate to severe cases and is not indicated in the current mild case presenting with just productive cough, but tacrolimus level is high in the current case, so, I will reduce the dose to attain a level between 7-10 ng/ml in the first 3 months after transplantation
– No need to increase the dose of steroid in the current patients since the patient has non severe symptoms
– Specific antiviral therapy (oral nimatrelvir/ritonavir or intravenous remdisvir) is indicated in mild to moderate cases if the followings are met
1- Duration from symptom onset is ≤5 days for nimatrelvir/ritonavir , or ≤ 7 days for remdisvir (patients who are > 7 days from the onset are treated with supportive measures only)
2- Patients are at risk of progression to severe disease including:
Patients who are immunosuppressed (SOT, HIV)Patients with multiple comorbidities like cancer, DM, smoking, pregnancy , TB, cerebrovascular disease, bronchial asthma, COPD, renal failure, heart failure and liver failurePatients >65 years oldPatients > 50 years and unvaccinated The choice between the 2 drugs depends on the followings
1- Duration elapsed from symptom onset
If within 5 days from the symptom onset both can be given with preference of nimatrelvir/ritonavir (nimatrelvir 300 mg and ritonavir 100 mg twice daily for 5 days)If in the 6th or 7th day after onset of symptoms remdisvir is preferred 2- Renal function tests
In patients with GFR 60 both can be given with preference of nimatrelvir/ritonavir (nimatrelvir 300 mg and ritonavir 100 mg twice daily for 5 days)In pateitns with GFR between 30-60 both can be given with preference of nimatrelvir/ritonavir (nimatrelvir 150 mg and ritonavir 100 mg twice daily for 5 days)In patietns with GFR < 30 remdisvir is preferred (200 mg IV in the first day then 100 mg daily for another 2 days) since nimatrelvir/ritonavir is contraindicated3- Liver function tests
In patients with advanced liver faliuer child C, remdisvir is preferred In patients without advanced liver failure both can be given with preference of nimatrelvir/ritonavir (nimatrelvir 300 mg and ritonavir 100 mg twice daily for 5 days)4- Drug-drug interactions
Nimatrelvir/ritonavir are potent CYP3A inhibitors and have several drug-drug interactions so we have to check the drugs given concomitantly and if there is contraindication for coadmisntarationand the other drug is vital and can not be withdrawn for the duration of therapy and 3 days after sdiscontinuation, remdisvir will be preferred In the setting of transplantation, nimatrelvir/ritonavir increase the trough level of CNI and thus the dose of CNI should be reduced once we introduce this drugs.So … in the current
I will asses the severity of infection using 6 min exercise and O2 saturationI will reduce the dose of tacrolimus markedly since the trough level is already high and I will start antiviral therapy that may further increase the level of CNI and follow up the level every 3 days till stopping the antiviral therapy and stabilization of the levelI will start oral nimatrelvir/ritonavir for 5 days
I like your clinical approach.
I like the following modification in immunosuppression: reduction of tacrolimus. But you have not mentioned stopping MMF for few days. I am not sure if this patient would really need anti-COVID drug.
The management plan for this case is based on current guidelines for the management of pneumonia in kidney transplant patients.
The use of lopinavir/ritonavir has been shown to be effective in improving outcomes in patients with SARS-CoV-2 infection
oseltamivir is the drug of choice for prophylaxis and treatment of SARS-CoV-2 infection in transplant recipients
It is recommended that immunosuppressant drugs should be adjusted as needed to prevent rejection and to maintain adequate graft function.
Furthermore, close monitoring of vital signs, laboratory tests and chest X-rays are necessary to ensure the patient is responding well to treatment and to prevent complications
Your reply is rather limited. It does not address all the concerns.
I like to believe that you would effect the following modification in immunosuppression: reduction of tacrolimus and stopping MMF for few days.
Impairment of T-cell immunity due to effect of immunosuppressive agent increase risk of severe bacterial & viral infection & infect-related death among SOT recipients.
Kidney transplant recipients mortality due to COVID-19 range 13-30% & hospitalization 32-100%.
Immunosuppression management during COVID-19 pandemic is challenging & several factors should be considered during this including: patient age, severity of infection, associated co-morbidities & time post transplantation.
Management:
The patient acquired COVID-19 infection early post transplant period(first 3 months) which is very crucial period regarding manipulation of immunosuppression.
Severity of infection should be identified( CBP, CRP, ferrite, IL-6 level & oxygen saturation).
The patient had mild symptoms so he can managed at home with close follow-up.
MMF should be discontinued, tacrolimus dose reduced(high trough level) with monitoring of renal function.
Good hydration.
He should call medical advise if there is any change in his symptoms e.g. dyspnea, high fever.
References:
Banerjee D., Popoola J., Shah S., Ster I., Quan V., et al. COVID-19 infection in kidney transplant recipients.Kidney Int., 2020;97(6):1076-1082.
Pinchera B., Spirito L., Ferreri L., Rocca R., Celentano G., et al. SARS-CoV-2 in Kidney Transplant Patients: A Real-Life Experience.Forntiers in Medicine, 2022.
How would you manage this case? This patient:
o Had a history of Wegner’s granulomatosis
o Presented 2 months after transplantation only with productive cough, no other symptoms
o Clinical examination was unremarkable
o Normal kidney function and clear chest-x-ray
o High tacrolimus trough level
o And confirmed to be COVID-19 (positive SARS-CoV-2 RNA)
This transplant patient is at a high risk of infection due to:
1. Immunosuppression
2. Underlying CKD
Management of COVID-19 (mild infection):
o CBC (lymphopenia), CRP, s.ferritin, and IL-6
o Outpatient management with self-isolation and advice to drink a lot of fluids
o Discontinue MMF
o Reduction of tacrolimus dose
o Monitoring of renal functions and tacrolimus level
o Return back to the transplant unit if any new symptoms appear
References
1. Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
2. Demir, E., Ucar, Z.A., Dheir, H. et al. COVID-19 in Kidney Transplant Recipients: A Multicenter Experience from the First Two Waves of Pandemic. BMC Nephrol23, 183 (2022). https://doi.org/10.1186/s12882-022-02784-w
This current case is ( S/P LRRTX in 2/2020 with SARS-COV-2 RNA +ve ): Indications for hospitalization; -This patient is COVID-19 with mild disease that does not warrant hospital-level care; -This patient need self-isolate at home and recover at home is preferred. Evaluation with further investigation; -Complete blood count (CBC) with differential, with a focus on the total lymphocyte count trend, daily, -Basic metabolic panel daily -Hepatic panel every other day (or daily if elevated or in the intensive care unit) -C-reactive protein (CRP) – Ferritin -Lactate dehydrogenase -Prothrombin time (PT)/partial thromboplastin time (PTT)/fibrinogen/D-dimer -Troponin -Electrocardiogram (ECG), with at least one repeat test after starting any QTc-prolonging agent Thromboprophylaxis; if high risk forvenous thromboembolism. Antipyretics; acetaminophen for fever reduction rather than non-steroidal anti-inflammatory drugs (NSAIDs). Continuing chronic medications; Patient who is on an ACE inhibitor or ARB for another indication should not stop his medications -Continue statins in hospitalized patients with COVID-19 who are already taking them, also continue aspirin unless there is concern for bleeding risk. Monitoring Po2 Sat. for assessment for Oxygen requirement; requested ABG , (target Po2 sat. ≥ 94%). Management of hypoxemia; Patients with severe disease often need respiratory support. Infection control; is an essential component of management of patients with suspected or documented COVID-19. Treatment this case with mild severity; -Supportive management with good hydration, -Stop Mycophenolate mofetil and continue CNI and steroid, -Adjustment of Tac. Trough to ( 4–6 ng/dL) , stop one or two doses till level decrease within the target range. -If worsening and increase severity (required ITU), will stop CNI and increase the steroid dose to a stress dose and shifting to IV. -COVID 19 treatment; ( by Pulmonology review using medications such as (hydroxychloroquine, azithromycin , Tocilizumab and others) & keep in mind drug-drug interaction. -Strict monitoring for Graft function tests , FK level. References; 1-D. K. Brady et al. A guide to COVID-19 antiviral therapeutics: a summary and perspective of the antiviral weapons against SARS-CoV-2 infection, The FEBS Journal (2022) Federation of European Biochemical Societies. doi: 10.1111/ febs. 16662. 2-Demir, E., Ucar, Z.A., Dheir, H. et al. COVID-19 in Kidney Transplant Recipients: A Multicenter Experience from the First Two Waves of Pandemic. BMC Nephrol 23, 183 (2022).
Patient had history of COVID-19 positive
need evaluation to check oxygen saturation
ABG
CBC for lymphopenia/ ESR/ CRP/ d. dimmer / procalcitonin level and LDH, LFT
COVID-19 PCR and igG, IgM, INR
CT chest
Management
Good hydration Antiviral therapy, anticoagulant, intravenous immunoglobulin, and tocilizumab to be considered reduce dose of tacrolimus to reach target level between (5-7), stop MMF and intravenous dexamthazone
How would you manage this case?
The patient is positive for COVID but has mild symptoms. I will request the CBC, procalcitonin, CRP, LDH, renal function, liver function, coagulation profile, and ferritin.
The treatment will depend on the lab results and the clinical manifestations.
mild cases like this one with normal inflammatory markers: reduce tacrolimus (13 is high) and reduce MMF to 250 mg bid and close observation at home for (fever, diarrhea, and SOB).
If any deterioration, the patient should be admitted to the hospital and stop MMF and keep the tac level 3-5
Hospitalized individuals with mild to severe, symptomatic COVID-19 may benefit from the same treatments as non-hospitalized patients. A large randomized controlled study indicated that a brief course of dexamethasone (6 mg daily for up to 10 days) enhanced survival in hospitalized severe COVID-19 patients who were mechanically ventilated or needed supplementary oxygen.
Tocilizumab or baricitinib with dexamethasone is indicated for severe or critical COVID-Immunosuppressive drugs including dexamethasone, tocilizumab, and baricitinib should be watched for secondary infections.
COVID-19-infected transplant recipients should get therapeutic anticoagulation like other hospitalized patients. COVID-19 patients with platelet counts <50,000 cells/μL should not get therapeutic anticoagulation. Physicians treating thrombocytopenia should follow hospital anticoagulation procedures.
In hospitalized COVID-19 patients, the Panel recommends remdesivir, dexamethasone, tocilizumab, baricitinib, and anticoagulation.
Interactions
Calcineurin inhibitors (cyclosporine, tacrolimus) and mTOR inhibitors (everolimus, sirolimus) used to prevent allograft rejection have limited therapeutic indices. Drugs that inhibit or stimulate cytochrome P450 (CYP) enzymes or P-glycoprotein may cause clinically significant
drug-drug interactions, requiring therapeutic drug monitoring and toxicity or rejection assessment. For mild to severe COVID-19 in nonhospitalized individuals at risk of disease progression, ritonavir-boosted nirmatrelvir (Paxlovid) is recommended for 5 days. Due to ritonavir, this regimen may cause complicated drug-drug interactions with concurrent medicines.
Ritonavir, a potent CYP3A inhibitor, boosts nirmatrelvir to a SARS-CoV-2-effective concentration. Ritonavir may also boost calcineurin and mTOR inhibitor concentrations during therapy and for three days thereafter. Increased medication concentrations may cause significant and even fatal drug toxicities.
RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2021;397(10285):1637-1645. Available at:
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 a productive cough and 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.
How would you manage this case?
A case of post Kidney transplant with SARS-COV-2 RNA positive and productive cough with history of Wegner’s granulomatosis. We should classify our patient according to his clinical manifestation:
1-Asymptomatic patients and patients with mild disease (oxygen saturation above 93%, no lung involvement on chest computed tomography) were followed up in the outpatient clinic weekly.
2-Patients with moderate disease (oxygen saturation above 90%, respiratory rate under 30 breaths/min) were hospitalized in the first wave of the pandemic and followed up in the outpatient clinic in the later period because of hospital overcrowding.
3-Hospitalization were severe disease (oxygen saturation under 90%, respiratory rate above 30 breaths/min), cytokine storm (persistent fever, high or increasing CRP, ferritin, and D-dimer, abnormalities in liver function tests, hypofibrinogenemia with cytopenia in the forms of lymphopenia and thrombocytopenia). Our patient should be treated with supportive treatment and treated as outpatient(by telemedicine), no need for hospitalization.(group 1 ).
= A protocol was used to :manage immunosuppression, antiviral, and cytokine‐targeted therapy
=Stop Mycophenolate mofetil and continue CNI and steroid , if worsening and our patient being in sever condition , will stop CNI and increase the steroid dose and shifting to IV.
=Trough levels were adjusted as 4–6 ng/dL for tacrolimus( here we need to decrease tacrolimus dose).
=COVID 19 treatment by chest physician using medications such as (hydroxychloroquine, azithromycin Tocilizumab and others) should bear in mind drug-drug interaction.
=Strict follow up for Renal function test, urine PCR and tacrolimus level. References:
1-2-Demir, E., Ucar, Z.A., Dheir, H. et al. COVID-19 in Kidney Transplant Recipients: A Multicenter Experience from the First Two Waves of Pandemic. BMC Nephrol 23, 183 (2022). https://doi.org/10.1186/s12882-022-02784-w.
2-Study of Scientific Board Republic of Turkey, Ministry of Health. COVID-19 (SARS-CoV-2 INFECTION) GUIDE. April 14th, 2020, Ankara, Turkey.
3-Semenzato L, Botton J, Drouin J, et al. Chronic diseases, health conditions and risk of COVID-19-related hospitalization and in-hospital mortality during the first wave of the epidemic in France: a cohort study of 66 million people. The Lancet Glob Health Regional Health – Europe. 2021;8:100158. https://doi.org/10.1016/j.lanepe.2021.100158.
Which category did you place this index case?
You put him in group one and suggested cytokine control antivirals?
you correctly reduced TAC and dc. MMF.
He can be managed by Tele medicine.
Thanks professor :Dawlat.
1-Our patient should be categorized by clinical assessment and according to O2 saturation (group 1) and group 2 in the second wave, no hospitalized.
2-Regarding cytokine control therapy is considered apart of the general protocol and not specific to our case.
3-Tele medicine enables video or phone appointments between a patient and their health care practitioner to decrease load on health care system and decrease rate of infection
Ghufran Aref Saeed et al., Correlation between Chest CT Severity Scores and the Clinical Parameters of Adult Patients with COVID-19 Pneumonia, Radiology Research and Practice Volume 2021, Article ID 6697677, 7 pages https:// doi. org /10.1155/2021/6697677
D. K. Brady et al. A guide to COVID-19 antiviral therapeutics: a summary and perspective of the antiviral weapons against SARS-CoV-2 infection, The FEBS Journal (2022) Federation of European Biochemical Societies. doi: 10.1111/ febs. 16662
Thank you, dear Prof. Ahmed
The patient is stable & not in any acute distress. Therefore, I will observe him in an outpatient setting. Arrangements for inpatient or specialized center admission should be made clear to the patient in case of any deterioration or desaturation occurs.
1. I would perform a non-contrast-enhanced CT scan of the chest to assess the progression of lung disease
2. I would request arterial blood gases to assess how the pulmonary gas exchange is doing since COVID-19 can occur with silent hypoxemia
3. I would not start Nimetravir + Ritonavir (Paxlovid) due to prohibitive drug interactions with immunosuppressive drugs and which could lead to graft dysfunction. Oral molnupiravir is an option for patients who are not yet on oxygen therapy.
Remdesivir (associated or not with Baricitinib) can be performed. If there is no progression and need for oxygen therapy, do it for three days, if there is evolution, expand to five days and associate corticosteroids.
4. Decreasing immunosuppression is a necessity, as measuring serum levels and considering drug interactions.
5. Clinical follow-up in the hospital with respiratory isolation with negative pressure to assess respiratory progression.
6. Subsequent immunization following local protocols
Professor, immunosuppressed patients are at high risk for complications. The patient is currently doing well clinically, which would indicate the use of Remdesevir on a three-day regimen to stop disease progression (Gottlieb et al).
Here in Brazil we have done it for patients undergoing bone marrow transplants or using antiplasmacytic drugs.
With the withdrawal of Evusheld from the market and the difficulty of entry of Paxlovid and Molpurinavir, Remdesivir became the necessary strategy (and the only one).
Paxlovid has many interactions with immunosuppressants, making Molnupiravir the best drug, but with much lower efficacy compared to the others.
With the difficulty in accessing specialized care, he would remain hospitalized until he defined the necessary care and monitored the evolution of the lung disease.
Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients. Gottlieb RL, Vaca CE, Paredes R, Mera J, Webb BJ, Perez G, Oguchi G, Ryan P, Nielsen BU, Brown M, Hidalgo A, Sachdeva Y, Mittal S, Osiyemi O, Skarbinski J, Juneja K, Hyland RH, Osinusi A, Chen S, Camus G, Abdelghany M, Davies S, Behenna-Renton N, Duff F, Marty FM, Katz MJ, Ginde AA, Brown SM, Schiffer JT, Hill JA; GS-US-540-9012 (PINETREE) Investigators.
N Engl J Med. 2022 Jan 27;386(4):305-315. doi: 10.1056/NEJMoa2116846. Epub 2021 Dec 22. PMID: 34937145
This is a case of confirmed COVID-19 with mild respiratory symptoms and good kidney function. This could have been managed as an outpatient case, while the patient must be well-informed of deteriorating signs like fever and persistent reduction in saturation.
However, because of risk factors like CKD/ transplant, and background etiological cause of CKD (Wegener granulomatosis), I will admit and manage as follows
Withold antimetabolite, MMF
Oxygen if the Spo2 < 90%
Continue with tacrolimus
Change to Dexamethasone at a dose range of 6-20mg
Inhaled corticosteroid particularly for those with Asthma
Close monitoring of kidney function
Close monitoring of blood glucose level
Remdesivir at three doses for three days for those that have the risk of progression like the index case, but has to be initiated within seven days of the beginning of symptoms
Baricitinib plus Remdesiver has also been used with some positive outcomes, particularly for the hospitalized patient
High titer convalescence titer can be used with the exception of those collected with individuals with Omicron or Delta variant
Hydroxychloroquine plus erythromycin. They both received some attention as possible antiviral agent but clinical trials have not suggested any benefits
If the patient is on anticoagulant or antiplatelet, he or she can continue during the treatment
Advice on COVID-19 vaccination after recovery from acute infection
References
Webb SA, et al. Glucocorticoid Dose in COVID-19: Lessons from Clinical Trials During a Pandemic. JAMA. 2021
Kalil AC, et al. Baciritinib plus Remdesivir for Hospitalized Adult with COVID-19. N Engl J Med. 2021: 384(9): 795-807
Thanks, Isaac I agree, he does not need hospitalisation and can be treated as an outpatient. Does he need to be treated with Remidisivir and big doses of steroids as you mentioned or just watch and wait? What do you think about the tac level?
Thank you prof Halawa for your response
He will definitely not need Remdesivir because of mild symptoms now, except if he deteriorated
The steroid dose will not exceed 6mg OD for the mild case
The Tacrolimus trough level will be kept at 4-6ng/ml with close monitoring of kidney function
How would you manage this case?
A. Hospitalization and isolation
B. Monitoring i.e RR, HR, SpO2, hydration, urine output
C. Investigation
– CBC, CRP
– RFT, LFT
– Tacrolimus drug level
– D- dimer, IL- 6 level
– HRCT of chest
– Blood & Urine C/S
D. Supportive treatment i.e adequate hydration, respiratory support as require
E. Modification of immunosuppression (Stop MMF, tacrolimus trough level 4-6 ng/dl, if require oxygen increase dose of prednisolone)
F. Thromboprophylaxis
G. Remdicivir and dexamethasone in case of requiring respiratory support
Substantiate your answer
Though this is mild case, require hospitalization and thromboprophylaxis as this is high risk patient.
What is the role of anticoagulant in post-transplant COVID infection?
According to ACH society Anti coagulation is recommended in COVID infected patients with moderate to severe infection.
Also those already on antiplatelet and anticoagulation should be continued.
How to manage this case with COVID-19?
Will advise admission,
General management,
Like IV fluid,
Antipyretics,
Multivitamins,
Prophylactic antibiotic to prevent super-infection,
High dose steroid,
Antiviral,
If high IL6 then Tocilizumab,
Immunosuppression dose reduction.
References;
1. https://www.nejm.org/doi/10.1056/NEJMoa2021436, N Engl J Med 2021; 384:693-704
DOI: 10.1056/NEJMoa2021436.
2. https://academicworks.medicine.hofstra.edu/publications/6200/.
Sir i would start anticoagulation, just to keep in mind the drug interaction.
Second, there is patch on right middle zone involving upper part of lower zone too.
I will hospitalize for further workup and treatment.
Management
Live donor renal transplant recipient, on triple immunosuppression, high Tac C0 level.
Presented with cough, tested positive for COVID
Clinical examination unremarkable – check respiratory rate, SpO2.
HRCT chest – helps risk stratification and Tt planning.
Get CBC (Leucopenia, Thrombocytopenia) – to adjust drug doses.
baseline RFT, LFT, LDH, CRP, D-dimer should be checked
This patient being clinically stable – needs just home isolation, with advises for observing breathing difficulty.
Routine check-up of all vital signs, temperature, tachypnoea and oxygen saturation.
Patient can be in contact with treating team through telemedicine / telephonic consultation.
Mild to moderate illness with Spo2 >95% à need only monitoring.
High fever >4 days, hypoxia < 94% on room air needs admission to hospital, especially in high-risk cases (transplant patients)
IS Reduction: withhold MMF till recovery, Tacrolimus dose reduction, targeting C0 of 7-9; increase Prednisone to 10mg OD.
Treatment: drugs like macrolides, HCQS, Convalescent plasma are not recommended by ICMR (Indian council of medical research)
Hypoxic patients à Dexamethasone 6 mg IV OD x 7-10days prevents lung inflammation
IL6 levels monitored – indicator of cytokine storm syndrome (2nd week)
– Tocilizumab is recommended for elevated IL6 levels with cytokine storm
Anticoagulants – recommended for moderately to severe COVID
– with anticoagulants with LMWH and later oral anticoagulants for 6 to 12 months
REFERENCES:
1 – NIH; COVID 19 treatment guidelines, last updated Dec 1 2022.
2 – Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron 2021; 145(2): 192-198 doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
3 – RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
4 – Santana ANC, Takagaki TY, Barbas CSV. Incidence of fatal venous thromboembolism in antineutrophil cytoplasmic antibody-associated vasculitis. J Bras Pneumol. 2011;37(3):409-411
Dear All
What is the role of anticoagulation in the management of post-transplant COVID infection?
What about hospitalisation?
by Prof. Ahmed Halawa
What is the role of anticoagulation in the management of post-transplant COVID infection? in
For Covid-19 symptomatic – moderate to severe, and critically ill patients – anticoagulation has been recommended, as in any acutely ill, hospitalized patient (1).
This is important in COVID patients, also because of high association with thrombotic complications that lead to PET, NI, stroke and adds to mortality.
As per BTS guideline – all patients admitted for COVID-19 should be assessed for anti-thrombotic prophylaxis, and majority would require anticoagulant.
LMWH in therapeutic dose be used for patients requiring supplemental oxygenation; lower doses should be used in critical patients (on high-flow oxygen, CPAP, NIV or invasive ventilation) without any indication of therapeutic anticoagulation (2).
For Outdoor / home isolation patients
Those at risk of possible ischemia or infraction like PE, DVT à consider LMWH (unfractionated heparin if GFR <15ml/min); fondaparinux is preferable in patient with h/o of HIT. (4)
Patients already on anticoagulants, (for AF or VTE) à continue previous anticoagulants or switch to short acting agents in case of admission to hospital for COVID-19 infection, D-Dimer positive. (4-6)
Indications of hospitalisation for Covid-19 patients:
The indications for hospitalization in a COVID-19 patient include (3):
1. A room air oxygen saturation of <94%
2. Respiratory rate of >30.
3. PaO2/FiO2 <300 mmHg
4. Lung infiltrates >50%
References:
1. Chandra A, Chakraborty U, Ghosh S, et al. Anticoagulation in COVID-19: current concepts and controversies. Postgrad Med J. 2022 May; 98(1159): 395-402. doi: 10.1136/postgradmedj-2021-139923.
2. BTS Guidance on Venous Thromboembolic Disease in patients with COVID-19. Updated August 2021. British Transplantation Society. Available online: https://www.brit-thoracic.org.uk/document-library/quality-improvement/covid-19/bts-guidance-on-venous-thromboembolic-disease-in-patients-with-covid-19/
3. Covid-19 treatment guidelines. Available online:
4. https://files.covid19treatmentguidelines.nih.gov/guidelines/covid19treatmentguidelines.pdf
5. UpToDate
6. Schulman S, Sholzberg M, Spyropoulos AC, et al. ISTH guidelines for antithrombotic treatment in COVID-19. Journal of thrombosis and haemostasis: JTH. 2022 Oct;20(10):2214-25. PubMed PMID: 35906716.
7. Cuker A, Tseng EK, Schünemann HJ, et al. American Society of Haematology living guidelines on the use of anticoagulation for thromboprophylaxis for patients with COVID-19: March 2022 update on the use of anticoagulation in critically ill patients. Blood advances 2022 Sep 13; 6(17): 4975-82. PMCID: PMC9236618.
Thrombotic complications (arterial and venous) are common in patients admitted to hospital with COVID-19 and are an independent predictor of poor outcome.1 Microvascular thrombi also contribute to organ dysfunction, including acute respiratory distress syndrome.
The pathogenesis of thrombosis in COVID-19 is intimately linked with the inflammatory response to the virus, endothelial infection, activation, and injury as well as hypercoagulability.2 Recognition that thrombosis is a key contributor to clinical deterioration and death has led to global interest in whether escalated anticoagulation dose or extended duration improves patient outcomes.
Early in the COVID-19 pandemic, published guidelines were heterogeneous with some, in the absence of evidence, recommending increased anticoagulation doses (particularly in critical care), stratifying dose by D-dimer results, or extended post-discharge thromboprophylaxis, or both.3 Since then, randomised controlled trials have focused on all phases of illness—from the community, to hospital admission, when critically ill, and post-hospital discharge—so that high-quality evidence is now informing clinical practice. From these trials, it has become clear that efficacy and safety of antithrombotic treatments depend on timing with respect to illness severity and dose, and that the mechanism of action might also be important.
For non-critically ill patients hospitalised with COVID-19, therapeutic-dose heparin appears beneficial, with a high probability of reducing the need for organ support and the progression to intubation and death, regardless of D-dimer results
.4 Results from two subsequent randomised controlled trials have also supported the role of therapeutic-dose heparin in this cohort.5, 6 By contrast, in critically ill patients, therapeutic-dose heparin did not improve outcomes and there was a high probability of harm.7 The INSPIRATION trial did not demonstrate benefit of intermediate-dose heparin compared with conventional low dose in this critically ill patient group.8
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02503-4/fulltext
SARS COV19 viral infection post transplantation is commonly associated with grim prognosis attributed to immunosuppressive status. The disease might progress to severe respiratory disease with respiratory failure culminating in higher mortality and morbidity. Similarly, AKI risk is mounting in post-transplant patients infected with Covid 19 virus. However, management is entirely dependent on severity of presentation. In our patient as far as he is stable with no respiratory symptoms, particularly dyspnea or tachypnea and normal chest xray,
The main line of management:
1] self-isolation,
2] close observation, for respiratory symptoms, desaturation and hemadynamic stability.
3] to stop anti-metabolite MMF and reduce dose of Tacrolimus.
4] No indication is there to increase dose of corticosteroid.
5] anti-coagulant prophylaxis is indicated as early as possible due to the higher risk of thromboembolic disease.
6]close observation of renal function as AKI risk is soaring.
in case of clinical deterioration of the patient with dyspnea, tachypnea or desaturation, then admission to hospital is indicated with multidisciplinary plan of care, including close observation of inflammatory markers in addition to clinical status. such as:
1] ferritin
2] CRP more than 120.
3] neutrophil/ lymphocytes count of more than 3/1
4] d-dimer
Reference:
1] http://www.BTS.UK. updated 2020.
· How would you manage this case?
COVID 19 early post transplant, within 2months, in the first few months of COVID 19 era with little experience on that.
Careful history of her illness, duration, recent travel, contact with sick person. His immunological history, history of infection, rejection.
Management should be according to local guidelines, isolation, admission, reduction of immunosuppression (FK level 8-10), hold MMF if low risk of rejection and/or continuous fever or desaturation.
Prophylactic anticoagulation according to local guidelines and personal risk of DVT, as it is known for SARS COV2 to increase risk of VTE.
· Substantiate your answer
References
MOH KSA local protocols for SARS Cov 2 infection
Q1: patient with a history of Wegner and kidney transplantation infected by SARS-Cov.2 should be admitted to the hospital. Performing complete laboratory tests and HRCT scans. O2 saturation should be measured and if needed should receive supplemental O2.
Reduction of immunosuppression by stopping MMF and even reduction of tacrolimus according to its level is recommended. Starting remdesivir for COVID-19 infection and proper antibiotics. Prophylactic anticoagulation should be considered to measure CRP, d-dimer and fibrinogen, and dexamethasone, and if indicated even start tocilizumab.
Management of the patient
Patient has mild symptoms of covid 19.
In the kidney transplant population, considerable proportions who had contracted SARS-CoV-2 developed an acute kidney injury (AKI).
Among 52 case reports reviewed, 63% of patients had been diagnosed with an AKI during their hospitalization.
Predictors of mortality among kidney transplant patients with SARS-CoV-2 infection were generally similar to those of the general population.
In factors specific to kidney transplant recipients, shorter span of time between transplant and COVID-19 infection, deceased donor transplant, diabetes, and previous antirejection therapy were associated with increased mortality.
Active cytomegalovirus coinfection and bacterial coinfections were also shown to complicate and worsen the prognoses of kidney transplant patients.
management
– hospital admission in isolation room.
-measurement of oxygen saturation , temperature.
-Good hydration
– Antipyretics , mucolytics.
– Lab investigationCBC , CRB , LDH . FERRITIN , D dimmer …etc.
-monitor kidney function and ABG.
– stop MPA/MMF due to its implications in suppressing the response of T-lymphocytes needed to mount an immune response to SARS-CoV-2.
-reduce tacrolimus dose to keep trough level 5-7ng/ml
. it was found that in patients who received anti-COVID-19 therapeutics, the tacrolimus doses had to be adjusted due to drug-drug interaction.
– Aspirin prophylaxis is recommended as patients with COVID-19 are at higher risk of blood clots especially in this patent as he had Wegner’s granulomatosis.
– In the treatment of COVID-19 in kidney transplant patients, reports of use of tocilizumab, remdesivir, low-dose methylprednisolone, convalescent plasma therapy, colchicine, and favipiravir have been published. However, most of these positive outcomes were observed in either case studies or small cohorts, and the use of any of these treatments should be considered on a case-by-case basis.
reference
DeFelice, Gina; Vijay, Adarsh,*. Coronavirus-19 infection in kidney transplant recipients: A comprehensive review. Indian Journal of Urology 38(2):p 110-114, Apr–Jun 2022.
· How would you manage this case?At first, it is necessary to classify the patient to define where the follow-up will be: – Mild and moderate cases without comorbidities: it could be conducted on an outpatient basis, with a reduction in the MMF and weekly consultation- Moderate cases with comorbidities (hypertension, diabetes, peripheral vascular disease): patient should be hospitalized, monitored regarding the need for oxygen therapy, MMF suspended, corticoid therapy with dexamethasone and antiviral therapy with remdesivir, prophylactic anticoagulation- Severe case: oxygen therapy, discontinue MMF, start corticosteroid therapy with dexamethasone and antiviral therapy with remdesivir, therapeutic anticoagulation.In critically ill patients, we have an increased risk of pulmonary thromboembolism, but without formal indication of therapeutic anticoagulation due to the risk of bleeding. However, patient with a history of Wegener’s granulomatosis, which adds risk, and anticoagulation is interesting. REFERENCES:
1 – NIH;COVID 19 treatment guidelines, last updated Dec 1 2022.
2 – Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
3 – RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
4 – Santana ANC, Takagaki TY, Barbas CSV. Incidence of fatal venous thromboembolism in antineutrophil cytoplasmic antibody-associated vasculitis. J Bras Pneumol. 2011;37(3):409-411
The given recipient is a live donor renal transplant recipient with basic disease as GPA…. Patient is on tacrolimus based triple immunosuppression…The patient has presented with cough and has tested positive for COVID…
Detailed clinical examination is needed…Respiratory rate, SPo2 examination to assess for hypoxia…CBC to look for leucopenia…baseline RFT,LFT, LDH, CRP, d dimer should be done…IL6 levels can be monitored as to get prepared for cytokine storm syndome in the 2nd week if any…CT chest for risk stratification should be done..CXR shows some right middle and lower lobe GGO…
The initial management of this patient is basically home isolation…Routine check of all vital signs including oxygen saturation, temperature, and tachypnea…Patient can be in contact through telemedicine facilities as it was done during the pandemic in our hospital…Mild to moderate illness with Spo2>94% need only monitoring..High fever more than 4 days, hypoxia < 94% on room air needs hospital admission especially in high risk cases like renal transplant patients….
Treatments like macrolides, HCQS, Convalescent plasma are not recommended by ICMR(Indian council of medical research)….
If the patient has hypoxia, we need to give IV steroids Dexamathasone 6 mg IV OD to prevent lung inflammation… Tocilizumab is recommended for elevated IL^ levels with cytokine storm if any
The role of anticoagulants in COVID in renal transplant recipients: Recommended for moderatly to severe COVID ..with anticoagulants with LMWH and later oral anticoagulants for 6 to 12 months
pt should be admitted in isolation
full examination:
as RFT, LFT, CBC, CRP, procalcitonin , DD
Tac level
high resolution CT chest
management:
good hydration
reduction of tac and stop MMF
monitor Oxygen
dexamethason
antiviral as remdesivir
This is a confirmed case of COVID 19 with mild symptoms.
This patient can be treated in out patient basis with proper education about criteria of hospitalization. Isolation, self monitoring of oxygen saturation. These signs are persistent fever, respiratory distress and drop in oxygen saturation.
Management:
· Detailed history and clinical examination, history of contact with SARS2-CoV positive patients.
· ABG, O2 Saturation, D-Dimer, HRCT chest, CBC, (lymphopenia may be seen)
Urine Analysis, Urine and Blood C/S
CNI level, Ferritin, IL-6.
· Isolation and close monitoring of oxygen saturation, good hydration, anti pyretic
· Reduction/modification IS: stop MMF with close graft monitoring. Maintain trough level of Tacrolimus 4–6 ng/dL.
· Dexamethasone in those receiving respiratory support
· Anti viral options: Paxlovid, remdesivir, molnupiravir, favipiravir, ribavirin, & Kaletra.
References:
·Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
This COVID 19 case has been identified and has mild symptoms. If the patient is properly informed about the requirements for hospitalization, they can be treated on an outpatient basis. Self-monitoring of oxygen saturation in isolation.
Important parameters for determining the COVID-19 stratification includes saturation and signs of respiratory distress.
If the patient has moderate to severe respiratory symptoms, an HRCT or CTPA may be recommended to rule out complications.
Initial step is to reduce MPA or antimetabolite to immunity recovery and self-defense, and the high level of tacrolimus must be adjusted to avoid secondary bacterial infection or nephrotoxicity.
IV hydration to maintain euvolemia
Prophylactic anticoagulation
Empirical antibiotic such as azithromycin could be helpful as immunomodulator.
Steroid is indicated in patients with oxygen requirement or severe cases and during cytokine storm.
Selection of antiviral therapy is given in agreement with ID consultant.
Multiple comorbidities, including cancer, diabetes, tobacco use, pregnancy, tuberculosis, cerebrovascular disease, bronchial asthma, COPD, renal failure, heart failure, and liver failure, are present in patients with multiple comorbidities. >65-year-old have been linked to higher risk of disease progression.
The use of Remdisivir has been shown to decrease viral load, and subsequent viral complications.
In case of cytokine storm (high persistent fever, CRP, D-dimer, hypofibrinogenemia, and high ferritin) –early initiation of dexamethasone 6 mg per day for 10 days.
post transplant covid 19 infection with cough
monitor fever and SPO2
persistent fever 100F and spo2 less than 90% on room aur are bad signs and need hospitalisation
covid 19 is prothrombogenic condition and after hospitalisation will be put on fractionated heparin
Antiplatlets on OPD basis is not not a standard practice
management is mainly supportive and IS is continued
in general recovery is as good as general population if detected in early phase
To admit to the hospital in isolation.
Investigations such as:
· Request HRCT
· Sputum culture rule out supper added infection
· FBC
· Renal function
· Procalcitonin
· CRP
· Ferritin
· D dimer
· Tacrolimus level
· Blood suger
· Liver function test
· Urine microscopy and culture
Reduce Tac dose by 50%, stop MMF
Hydration
Prophylactic anticoagulation
Repeat CXR if condition changes
monitor oxygen saturation
In case condition changed, and the patient requires respiratory support
dexamethasone 6 mg for 10 days
Antiviral Remdesivir should be added.
In case of elevated inflammatory markers (IL) Sotrovimab ( monoclonal antibodies) can be prescribed (if oxygen saturation is not dropped.
References:
Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
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 a productive cough and 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.
History and Physical examination
Routine labs CBC ,Creatinine and BUN, AST ,ALT ,LDH, CRP
Coagulation profile ,RBS ,serum electrolytes, ferritin ,IL6
Tacrolimus level
HR Chest CT
Management included
This patient considered high risk as he is immunocompromised with hx of Wegner’s granulomatosis and he should be hospitalized in isolation room with close
Vital signs spo2 should kept above 94 %
Daily labs to assess rejection
supportive treatment (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.
Decrease Tacrolimus level to reach from 4 to 6 ng/mL
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.
short course of dexamethasone (6 mg once daily for up to 10 days) improved survival in hospitalized people with severe COVID-19 who were mechanically ventilated or who required supplemental oxygen.
Tocilizumab or baricitinib used in combination with dexamethasone is recommended for some patients with severe or critical COVID-19.
Because dexamethasone, tocilizumab, and baricitinib are immunosuppressive agents, patients who receive these medications should be closely monitored for secondary infections.
Therapeutic anticoagulation for transplant recipients who are hospitalized for COVID-19 should be managed similarly to anticoagulation for other hospitalized patients. Patients with platelet counts <50,000 cells/µL should not receive therapeutic anticoagulation to treat COVID-19. Clinicians should follow hospital protocols for managing anticoagulation in patients with thrombocytopenia.
antimicrobials used to prevent or treat opportunistic infections.
Reference
COVID 19 guidelines Special Considerations in Solid Organ Transplant, Hematopoietic Cell Transplant, and Cellular Immunotherapy Candidates, Donors, and Recipients
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 a productive cough and 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.
Issues/ concerns:
– 50yo male, Wegener’s granulomatosis, LDKTx Feb 2020
– April 2020: presented with productive cough, positive SARS-CoV-2 RNA
– clinical exam unremarkable
– CXR clear, UECs stable
– medication: tacrolimus trough 13.4ng/mL, MMF 500mg BD, prednisone 5mg OD
How would you manage this case? (1-4)
– multidisciplinary approach: infectious disease team, chest physician
– detailed history and physical examination
– baseline investigations: FHG, ESR, CRP, procalcitonin, serum ferritin, D-dimers, coagulation profile, LFTs, serum LDH, sputum gene xpert, BGA, blood and urine culture, blood sugar
– imaging: HRCT chest to better assess parenchymal involvement
– assess for risk factors: old age, comorbidities, physical inactivity, male sex, low socioeconomic status, laboratory abnormalities (AKI, lymphopenia, thrombocytopenia, elevated liver enzymes, LDH, CRP, ferritin, IL-6, TNF, D-dimer, prothrombin time, troponins, CPK)
– approach to management is similar to that of the general population i.e., supportive care, use of antiviral medications
– severity of SARS-CoV-2 infection is affected by the type, combinations and intensity of immunosuppression: lymphocyte depleting antibodies and antimetabolites cause lymphopenia which is a risk factor for severe COVID-19 disease, mTORi and MMF decrease immune response to the vaccine
– there is no well-defined/ optimal approach when it comes to modifying the immunosuppressive therapy
– immunosuppressive regimen adjustment should be individualized depending on the disease severity, type of organ transplant, the specific immunosuppressive regimen used, time post-transplant, risk of acute rejection
– reduce or hold the antimetabolite especially in patients with lymphopenia i.e., ALC <700cells/mL
– continue with CNIs since they inhibit IL-1 and IL-6 pathways: Il-1 and IL-6 result in a severe, dysregulated immune response
– mTORi is thought to have some biological activity against SARS-CoV-2
– watch out for drug-drug interactions and the effects on the immunosuppressive therapy: more so with drugs that inhibit or induce CYP3A metabolism and/ or P-gp efflux
– the decision to reduce immunosuppression should be weighed against the risk of rejection
– COVID-19 itself increases the risk for acute graft rejection, an exaggerated intense inflammatory host immune response can contribute to the overall disease severity
– some SOT recipients recover without reduction in immunosuppression but this increases the risk of IRIS and rejection
– continued use of immunosuppression increases the risk of uncontrolled infection
– vaccination: ideal timing for vaccination in the post-transplant period remains unknown, but one can consider vaccinating 1 month post-transplant or 3 months after using ATG (T-cell depleting agent) or Rituximab (B-cell depleting agent)
Our case: (5)
– requires hospital admission and isolation given his risk factor profile
– baseline investigations and imaging as suggested above
– assess disease severity based on presence of symptoms suggestive of pneumonia, oxygen saturation, respiratory rate, findings on imaging
– monitor oxygen saturation and respiratory rate, oxygen therapy depends on the oxygen saturation
– IV antibiotics if there is a super-imposed bacterial infection
– IV hydration, GI prophylaxis, DVT prophylaxis
– hold MMF, target tacrolimus trough level of 2-4ng/mL, continue with the steroids
– if the patient develops severe disease, transfer to ICU, discontinue all immunosuppressive agent and increase steroid dose to prednisone 15-25mg/day or dexamethasone 6mg BD for 10 days but if the risk of rejection is high, consider low dose CNI
– remdesivir can also be considered: it is thought to reduce the viral load and also the risk of a cytokine storm
– tocilizumab enhances survival in case of a cytokine storm
Substantiate your answer
References
1. Kates OS, Haydel BM, Florman SS, Rana MM, Chaudhry ZS, Ramesh MS, et al. Coronavirus Disease 2019 in Solid Organ Transplant: A Multicenter Cohort Study. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2021 Dec 6;73(11):e4090-e9. PubMed PMID: 32766815. Pubmed Central PMCID: PMC7454362. Epub 2020/08/09. eng.
2. Nair V, Jandovitz N, Hirsch JS, Nair G, Abate M, Bhaskaran M, et al. COVID-19 in kidney transplant recipients. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2020 Jul;20(7):1819-25. PubMed PMID: 32351040. Pubmed Central PMCID: PMC7267603. Epub 2020/05/01. eng.
3. Gérard AO, Barbosa S, Anglicheau D, Couzi L, Hazzan M, Thaunat O, et al. Association Between Maintenance Immunosuppressive Regimens and COVID-19 Mortality in Kidney Transplant Recipients. Transplantation. 2022 Oct 1;106(10):2063-7. PubMed PMID: 35883236. Pubmed Central PMCID: PMC9521383. Epub 2022/07/28. eng.
4. Requião-Moura LR, Modelli de Andrade LG, de Sandes-Freitas TV, Cristelli MP, Viana LA, Nakamura MR, et al. The Mycophenolate-based Immunosuppressive Regimen Is Associated With Increased Mortality in Kidney Transplant Patients With COVID-19. Transplantation. 2022 Oct 1;106(10):e441-e51. PubMed PMID: 35765133. Pubmed Central PMCID: PMC9521389. Epub 2022/06/30. eng.
5. Elsayed HM, Wadee S, Zaki MS, Were AJO, Ashuntantang GE, Bamgboye EL, et al. Guidelines for the prevention, detection and management of the renal complications of COVID-19 in Africa. African Journal of Nephrology. 2020 06/09;23(1):109-26.
This is a confirmed case of COVID 19 with mild symptoms. This patient can be treated in out patient basis with proper education about criteria of hospitalization. Isolation, self monitoring of oxygen saturation. These signs are persistent fever, respiratory distress and drop in oxygen saturation.
Management:
· Detailed history and clinical examination, history of contact with SARS2-CoV positive patients.
· ABG, O2 Saturation, D-Dimer, HRCT chest, CBC, (lymphopenia may be seen)
Urine Analysis, Urine and Blood C/S
CNI level, Ferritin, IL-6.
· Isolation and close monitoring of oxygen saturation, good hydration, anti pyretic
· Reduction/modification IS: stop MMF with close graft monitoring. Maintain trough level of Tacrolimus 4–6 ng/dL.
· Dexamethasone in those receiving respiratory support
· Anti viral options: Paxlovid, remdesivir, molnupiravir, favipiravir, ribavirin, & Kaletra.
References:
·Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
References
A case of post Kidney transplant
with SARS-COV-2 RNA positive and productive cough
with history of Wegner’s granulomatosis.
Will need admission for close observation (ABG/O2Sat) and more workup (CT chest, and blood tests to look for severity of disease).
In General, we can treat this case with supportive treatment (good hydration and acetaminophen as needed)) and can be managed as outpatient with close follow-up (O2Sat at home) monitoring.
We should classify our patient as per clinical manifestation:
1-Asymptomatic patients
mild disease (oxygen saturation above 93%, no lung involvement on chest computed tomography) needs follow-up in the outpatient clinic weekly.
2-Patients with moderate disease (oxygen saturation above 90%, respiratory rate under 30 breaths/min) needs hospitalization during initial phase and followed up in the outpatient clinic in the later period.
3-Hospitalization in severe disease (oxygen saturation under 90%, respiratory rate above 30 breaths/min), cytokine storm (persistent fever, high or increasing CRP, ferritin, and D-dimer, abnormalities in liver function tests, hypofibrinogenemia with cytopenia in the forms of lymphopenia and thrombocytopenia).
How would you manage this case?
Management:
Discontinued MMF or decrease 50% and continue CNIs with close graft monitoring the patient (immunosuppression treatment should be individualized based on the careful assessment of each patient) Tacrolimus Trough levels adjusted as 4–6 ng/dL.
Drugs targeting immune response regulation:
Dexamethasone in those receiving respiratory support (invasive mechanical ventilation or oxygen alone): resulted in lower 28-day mortality
Drugs that preventing viral replicatation:
Paxlovid, remdesivir, molnupiravir, favipiravir, ribavirin, & Kaletra.
Remdesivir: The Adaptive COVID-19 Treatment Trial proved that remdesivir-treated patients had 31% faster time to recovery when compared to control
Case series and a small RCT suggested better outcomes with interferon and high-dose steroids in conjunction with supportive care.
References
1) Bitterman R, Kumar D. Respiratory Viruses in Solid Organ Transplant Recipients. Viruses. 2021 Oct 25;13(11):2146.
2) RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704.
3) Study of Scientific Board Republic of Turkey, Ministry of Health. COVID-19 (SARS-CoV-2 INFECTION) GUIDE. April 14th, 2020, Ankara, Turkey.
4)-Semenzato L, Botton J, Drouin J, et al. Chronic diseases, health conditions and risk of COVID-19-related hospitalization and in-hospital mortality during the first wave of the epidemic in France: a cohort study of 66 million people. The Lancet Glob Health Regional Health – Europe. 2021;
Management:
-Lab testing: CBC, ESR, D-DIMERS, LFTS, UECS, Sputum MCS/ZN staining, Ferritin, RBS, Amylase, Lipase ,D-Dimer
-If Covid 19 PCR +VE + URTI features ,we proceed for HRCT chest.
-An elderly patient, with kidney transplant & history of Wegner’s granulomatosis ;all predispose to severe infection, so this pt needs to be admitted for proper management.
-Resp support , IV dexamethasone.
– MMF discontinuation till COVID 19 PCR negative, at least 2 consecutive tests with improvement of symptoms.
-Decrease tac trough levels to 5-8ng/ml with stress doses of steroids.
– Remdesivir.
-DVT and Gastritis prophylaxis.
– Tocilizumab according to chest consultation.
-Monitoring of covidcomplications.;egAK,pancreatitis,MI,Arrythmias,coagulopathies ,vasculitis.
-Vaccination against COVID 19 following recovery.
References:
Saad I et al;COVID 19;breaking down a global health crisis ;Annals of clinical microbiology and antimicrobials;35(2021)
Halawa et al;Covid 19 in Kidney Transplant Recipients; Case series and brief review of current evidence .Nephron 2021;145(2);192-198
Hoeby P et al ;Recovery collaborative group; Dexamethasone in hospitalized pts with Covid 19.N Eng j med .2021 feb 25;384(8)693-704
Management
Kidney transplant recipient who tested positive for Sars-Cov2 RNA, CXR normal, kidney function stable and presented with a productive cough.
This patient will require admission for close observation and management, this is a 50 year old male kidney transplant recipient with history of wegners granulomatosis.
I will also order a HRCT for better characterisation of the lung involvement though the CXR is normal.
Other workups I will do in this patient will include:
This patient currently is stable thus will first stop the MMF and reduce the tacrolimus trough levels to be between 8-12ng/ml. The use of antimetabolites in SOT with Covid 19 have been associated with poor outcomes CNI may be continued since they inhibit IL1 and 6.
Incase the patient desaturates or requires mechanical ventilation then there will be a role of switching the steroids to IV dexamethasone. Dexamethasone has been shown to reduce the 28 day mortality in hospitalised patients on mechanical ventilation or requiring oxygen supplementation.
Antivirals like remdesivir can also be given if the patient requires oxygen supplementation. Remdesivir was associated with better outcomes than controls.
Other medication that can be considered are baricitinib- for cases that steroids are contraindicated to be given with remdesivir, tocilizumab- in cases of cytokine storm.
What is the role of anticoagulation in the management of post-transplant covid infection?
Anticoagulants are indicated in moderate to severe cases of Covid 19 infections due to the thrombogenic activity of Sars-Cov2 hence increased risk of pulmonary embolism and thromboembolism.
For patients hospitalised and doesn’t need oxygen supplementation then the recommendation is to use prophylactic dose of heparin. However patients who require oxygen should be on therapeutic dose of heparin.
References.
Coronavirus Disease 2019 (COVID-19) Treatment Guidelines
https://www.covid19treatmentguidelines.nih.gov/ on 3/26/2023
Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, Mafham M, Bell JL, Linsell L, Staplin N, Brightling C, Ustianowski A, Elmahi E, Prudon B, Green C, Felton T, Chadwick D, Rege K, Fegan C, Chappell LC, Faust SN, Jaki T, Jeffery K, Montgomery A, Rowan K, Juszczak E, Baillie JK, Haynes R, Landray MJ. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
2.Substantiate your answer
REF;
How would you manage this case?
this is covid pneumonia in immunocompromized patients above 50 years with AAV as a primary disease and on intense triple immunotherapy including MMF and tacrolimus with higher trough level
this patient needs hospital admission in an isolated room with close observation and asses for o2 requirements to send for inflammatory markers including CRP, FBC looking for lymphopenia, thrombocytopenia, LDH, DD test
HRCT may be considered if the patient became hypoxic to assess the level of lung involvement and rule out PE
start on consrevative medical therapy including hydration , heparin prophylaxis and if his CRP > 75 needs o2 therapy will consider dexamethasone 6 mg along with remidasevir for 5 -10 days
hold MMF and continue on tacrolimus adjusted dose along with perdnisolone
A normal CXR does not exclude lung involvement in COVID
A HRCT chest should be considered along with
Ferritin
LDH
As patient has productive cough and he is highly immunosuppressed with a possibility of worsening of clinical condition. In such scenario HOSPITAL ADMISSION is a better option
If HRCT chest confirms lung involvement
Remdesivir should be administered
Dexa should be reserved for oxygen dependent patients
All patients admitted to hospital should be given LMWH after careful assessment
Dose of Tacrolimus should be decreased as trough level is high
MMF can be withdrawn if HRCT chest confirms lung involvement
⭐ Case with COVID infection:
_Isolation to protect against spread of infection, health care providers must use appropriate PPE.
_Ensure good hydration , use of supportive therapy (antipyretics, IV fluids and oxygen therapy as needed).
_stop antiproliferative (MMF and AZA).
_in severe cases:
👉 Consider stoppage of CNI.
👉 consider high dose dexamethasone in suspected cytokine storm (6 mg/day) and assisted ventilation either CPAP or entubation and MV.
👉 consider antiviral as (remdisivir) to improve survival and rapid recovery.
_ add anticoagulant prophylactic dose to prevent thrombosis.
_Follow up serum LDH, ferritin, D dimer, CRP.
_follow up liver and kidney functions.
_Close monitoring of graft function.
How would you manage this case?
A KTR with uncomplicated COVID-19 infection in the early post-transplant period. He is vitally stable with clear CXR and stable KFT.
1. I will admit this patient aiming at isolation in the hospital beside supportive measures and close observation to guard against anticipated complications in COVID-19 infection.
2. I will adjust the dose of TAC to be in the range of 4-6 ng/ml. I will reduce the ant-metabolite dose(MMF) by 50%. I will keep him on prednisolone.
3. Required laboratory work-up in COVID-19 infection(1):
· 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.
4. Considering the outcome of the recovery trial is helpful in guiding the management plan of this patient(2):
a) Aspirin was added to the trial because it is used to prevent blood clots, patients with COVID-19 are at higher risk of blood clots forming in their blood vessels. It is also cheap and widely available, which make it a good candidate.
b) Tocilizumab reduces deaths in patients hospitalized with COVID-19. The study also showed that tocilizumab shortens the time taken for patients to be successfully discharged from hospital, and reduces the need for a mechanical ventilator.
c) Baricitinib reduces deaths in hospitalized patients. The RECOVERY team found that treatment with baricitinib reduced deaths by 13%. It also reduced the chance of progressing to invasive mechanical ventilation.
d) 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. Dexamethasone reduces deaths by up to one third.
References
1. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current EvidenceMuhammed Ahmed Elhadedy, Yazin Marie, Ahmed Halawa Nephron 2021;145:192–198 DOI: 10.1159/000512329
2. UK Search and Innovation ; The Recovery Trial https://www.ukri.org/
Dear All
What is the role of anticoagulation in the management of post-transplant COVID infection?
What about hospitalisation?
Anticoagulation post transplant COVID infection:
1- patient requires hospital admission:
Use VTE prophylaxis like non transplant
2- Patients who are progressively unwell and require ventilatory support
Consider therapeutic anticoagulation, if no contraindications
Reference: BTS guidance
https://bts.org.uk/wp-content/uploads/2022/01/Clinical-management-of-transplants-and-immunosuppression-28th-Januray-2022-003.pdf
Patients with COVID-19 are at higher risk of blood clots forming in their blood vessels. Aspirin was added to the recovery trial trial because it is used to prevent blood clots, . it is also cheap and widely available, which make it a good candidate.
isolation, either home isolation or in-ward isolation.
non-transplant patient may undergo home isolation when being stable and no need for supportive oxygen therapy.
SOT recipient will benefit more from isolation at hospital base to guard against anticipated complications of COVID-19 infection.
Thnxs prof,
Role of anticoagulants in Post-transplant COVID infection.
In outdoor patients
In case of warranted admission to hospital for covid infection
Rferences
UpToDate
⭐COVID 19 is well known to have thrombogenic activity, hence use of prophylactic anticoagulant is warranted especially in high risk groups (elderly, use of steroids or oral contraceptive therapy, hospitalized patients with severe infection), so it is indicated here.
.🎯 As regard hospitalization:
_indicated for severe cases with hypoxemia (requiring oxygen therapy or assisted ventilation).
_high risk patient as transplant recipient.
_patient with multi system affection or cytokines storm.
What is the role of anticoagulation in the management of post-transplant COVID infection?
Anticoagulation has been recommended in moderate to severe, and critically ill COVID-19 patients, as in any acutely ill, hospitalized patient (1). This is especially important in the context of COVID-19 being associated with coagulation dysfunction and consequent venous thromboembolism and pulmonary embolism. As per the British Transplantations society, all patients admitted for COVID-19 should be assessed for thromboprophylaxis, and majority would require it. Therapeutic low molecular weight heparin (LMWH) should be used for patients requiring supplemental oxygenation. Lower doses should be used in critical patients (on high-flow oxygen, CPAP, NIV or invasive ventilation) without any indication of therapeutic anticoagulation (2).
What about hospitalisation?
The indications for hospitalization in a COVID-19 patient include (3):
1. A room air oxygen saturation of <94%
2. Respiratory rate of >30.
3. PaO2/FiO2 <300 mmHg
4. Lung infiltrates >50%
References:
Covid 19 tx guidelines panel recommendations – Last updated Dec 1 2022.
REF ;
NIH;COVID 19 treatment guidelines, last updated Dec 1 2022.
– development of thrombosis during hospitalisation was a unique feature in Covid-19 patients compared with other viral infections
– individualise treatment, weigh risk vs benefit when deciding on the dose
– prophylactic dosing is preferred for ICU patients
– therapeutic dosing is preferred for non-ICU inpatients
– adjust dose according to weight and kidney function
– LMWH is generally preferred over other anticoagulants
– thromboprophylaxis is usually stopped at discharge
– no need for thromboprophylaxis for outpatients
– initiate therapeutic dose anticoagulation for documented VTE or high suspicion for VTE, continue for at least 3 months
– UFH is preferred for unstable patients with organ dysfunction
– LMWH or DOACs can be used in stable patients without organ dysfunction
References
1. Schulman S, Sholzberg M, Spyropoulos AC, Zarychanski R, Resnick HE, Bradbury CA, et al. ISTH guidelines for antithrombotic treatment in COVID-19. Journal of thrombosis and haemostasis : JTH. 2022 Oct;20(10):2214-25. PubMed PMID: 35906716. Pubmed Central PMCID: PMC9349907. Epub 2022/07/30. eng.
2. Cuker A, Tseng EK, Schünemann HJ, Angchaisuksiri P, Blair C, Dane K, et al. American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis for patients with COVID-19: March 2022 update on the use of anticoagulation in critically ill patients. Blood advances. 2022 Sep 13;6(17):4975-82. PubMed PMID: 35748885. Pubmed Central PMCID: PMC9236618. Epub 2022/06/25. eng.
COVID 19 is well known to have thrombogenic activity, hence use of prophylactic anticoagulant is warranted especially in high risk groups (elderly, use of steroids or oral contraceptive therapy, hospitalized patients with severe infection), so it is indicated here.
As regard hospitalization:
_indicated for severe cases with hypoxemia (requiring oxygen therapy or assisted ventilation).
_high risk patient as transplant recipient.
_patient with multi system affection or cytokines storm.
What is the role of anticoagulation in the management of post-transplant COVID infection?
Anticoagulants is recommended in moderate to severe cases and critically ill as COVID is associated with coagulopathy and thromboembolism
What about hospitalisation?
critically ill with lung infiltrates more than 50%
spo2 less than 94
RR more 30
Q1: in case of hospitalization like this case, prophylactic anticoagulation with LMWH is recommended.
Q2: hospitalization is necessary for high-risk cases like our patient and O2 sat<= 93%, RR>30, and more than 50% lung involvement.
Thank you prof
Role of anticoagulation in the management of post-transplant COVID infection?
As this is high risk patient require thromboprophylaxis even if mild case as covid -19 infection provoke coagulopathy.
What about hospitalisation?
This patient require hospitalization for close monitoring i.e RR, BP, SpO2, hydration, urine output, tacrolimus trough level even in mild case
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 a productive cough and 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.
How would you manage this case?
References
(1) Danziger-Isakov L, Blumberg EA, Manuel O, Sester M. Impact of COVID-19 in solid organ transplant recipients. Am J Transplant. 2021 Mar;21(3):925-937. doi: 10.1111/ajt.16449. Epub 2021 Feb 26. PMID: 33319449; PMCID: PMC9800718.
(2) Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
(3) RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
(4) Belsky JA, Tullius BP, Lamb MG, Sayegh R, Stanek JR, Auletta JJ. COVID-19 in immunocompromised patients: A systematic review of cancer, hematopoietic cell and solid organ transplant patients. J Infect. 2021 Mar;82(3):329-338. doi: 10.1016/j.jinf.2021.01.022. Epub 2021 Feb 4. PMID: 33549624; PMCID: PMC7859698.
Excellent Dr Mohamed
I agree with the treatment plan, especially the justification for admission to the hospital.
Management of Covid-19 infection in kidney transplant recipients
a) Paxlovid oral if the condition is mild without respiratory compromisation.
b) Remdisivir IV for 3 consecutive days if the condition deteriorates.
References
This is a repetition.
Management of Covid-19 infection
a) Paxlovid oral if the condition is mild without respiratory compromisation.
b) Remdisivir IV for 3 consecutive days if the condition deteriorates.
References
What about hospitalisation?
Wegener’s granulomatosis can be triggered by covid or any other infection. For that reason, I will admit this patient because the right perihilar area seems infiltrated (?!). The picture can be better evaluated with CT though not very necessary as long as the patient doesn’t have dyspnea or abnormal oxygenation. I will follow up the CBC, CRP, D-dimer, LSH and other biochemistry.
I will stop MMF and give either 8 mg dexamethasone or 40 mg prednisolone. TAC level is above the target; lowering the dose somehow with a follow-up of renal function is needed.
At that time, we did not have plenty of medications but Favipravir so that we could start it despite its controversy. Remedisivir is an option where available.
Monitoring of renal function and respiratory symptoms
supportive inhaler therapy and oxygen when needed
——
https://www.uptodate.com/contents/covid-19-issues-related-to-solid-organ-transplantation
What is the role of anticoagulation in the management of post-transplant COVID infection?
What about hospitalisation?
In the above case,patient has mild symptoms and COVID 19 test positive so to assess for severity-few tests like complete blood picture, renal and liver function tests ,D-Dimers ,inflammatory markers like CRP, serum ferritin, LDH, HRCT chest should be done .Treatment will depend on the severity of Covid.The above patient falls into mild category so should be managed as an outpatient case -just withholding MMF and reduction of Tacrolimus to 5-7ng/ml with supportive treatment for fever ,diarrhea and close monitoing of graft function. Counseling should be done that f condition deteriorates –ten immediately report to hospital for admission.
Hospitalized patients with mild-moderate patients will be managed with anti-coagulation along with supportive management –they may need dexamethasone up to 6 mg which may hasten recovery(RECOVERY TRIAL)For severe cases-Drugs which can be tried include Tocilizumab ,baricitinib ,Favipiravir, Molnupiravir, Nimatrelvir/ritonavir but have to be cautious about drug-drug interaction.
REFERENCES:
1- Banerjee D., Popoola J., Shah S., Ster I., Quan V., et al. COVID-19 infection in kidney transplant recipients.Kidney Int., 2020;97(6):1076-1082
2- RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, Mafham M, Bell JL,et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704.
What is the role of anticoagulation in the management of post-transplant COVID infection?
How would you manage this case?
This is a confirmed case of COVID 19 infection with mild symptoms. There are good renal functions. This case can be managed as outpatients. However he will be warned of clinical signs of deterioration . In that case he will require hospital admission. These signs are persistent fever and drop in oxygen saturation. AS he is on immune suppression and hospital admission can also be considered for better monitoring.
Patient will be advised for good hydration
Watching oxygen saturations and give oxygen if it is < 90%
HRCT Chets
Stop MMF and continue CNI
Watch TAC levels with target upto 4-6 ng/ml
Dexamethasone upto 6 mg OD
Inhalational steroids can be considered if saturation drops
Watching blood glucose and graft functions
Those at high risk of progression can have Remdesivir for 3 days
Watching for D Dimers and start anti coagulation if necessary,
Chloroquine and HCQ have been reported to have antiviral activity, to inhibit cytokine production, and to be associated with improved CT pulmonary images, a rapid decline in fever, and a quicker recovery period. The effect seems to be reinforced by azithromycin
Follow up is necessary to assess respiratory functions
COVID 19 immunization later
Nair V, Jandovitz N, Hirsch JS, Nair G, Abate M, Bhaskaran M, Grodstein E, Berlinrut I, Hirschwerk D, Cohen SL, Davidson KW, Dominello AJ, Osorio GA, Richardson S, Teperman LW, Molmenti EP. COVID-19 in kidney transplant recipients. Am J Transplant. 2020 Jul;20(7):1819-1825
Yes, as you suggest, I agree that you would consider stopping MMF for few days. However, I do NOT agree with your suggestion: hydroxychloroquine/chloroquine, azithromycin.
Please read my comment in the thread of second article of journal club in week 9 ridiculing a number of unproven treatments that have been suggested, when I wrote a short story of a dog believing its barking would trigger train to leave the station!
Typing whole sentence in bold or typing in capitals amounts to shouting.
Thank you Prof
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 a productive cough and 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.
How would you manage this case?
A case of post Kidney transplant with SARS-COV-2 RNA positive and productive cough with history of Wegner’s granulomatosis.
1st:
In Our Center I will admit any immunocompromised patient for close observation (ABG/O2Sat) and more workup (CT chest, Transplant ID opinion to start Remdesivir or not).
In General we can treat with supportive treatment (good hydration and acetaminophen as needed)) and treated as outpatient with close fu (O2Sat at home )monitoring and no need for hospitalization see next=>
We should classify our patient according to the clinical manifestation:
1-Asymptomatic patients and patients with mild disease (oxygen saturation above 93%, no lung involvement on chest computed tomography) were followed up in the outpatient clinic weekly.
2-Patients with moderate disease (oxygen saturation above 90%, respiratory rate under 30 breaths/min) were hospitalized in the first wave of the pandemic and followed up in the outpatient clinic in the later period because of hospital overcrowding.
3-Hospitalization were severe disease (oxygen saturation under 90%, respiratory rate above 30 breaths/min), cytokine storm (persistent fever, high or increasing CRP, ferritin, and D-dimer, abnormalities in liver function tests, hypofibrinogenemia with cytopenia in the forms of lymphopenia and thrombocytopenia).
High Risk Patient (Severity & Mortality) Factors:
Age > 55 years
Numerous pre-existing comorbidities
Hypoxia
CT showing extensive lung involvement.
Various laboratory test abnormalities
Biomarkers of end-organ dysfunction.
How would you manage this case?
Detailed history and comprehensive clinical examination
Any history of contact with SARS2-CoV positive patients.
ABCD, ABG, O2 Saturation and D-Dimer
CT thorax without iv contrast to DD Hge from infection
CBC, (lymphopenia may be seen)
Kidney function tests.
Urine Analysis, Urine and Blood C/S
CNIs level
TB (Mantoux, IGRA, and sputum culture) Screening
Fungal (PJP) (induced sputum or bronchoscopy for BAL) screening
Sr. Ferritin, IL-6.
CMV viral load.
LDH, Ferritin, CRP and procalcitonin
Management:
Admission in isolation room, under observation (ABG/ O2Sat)
Supportive medical therapy, good hydration (IV fluids and acetaminophen as needed).
Reduction of immunosuppressive medications or even discontinued.
Discontinued MMF or decrease 50% and continue CNIs with close graft monitoring the patient (immunosuppression treatment should be individualized based on the careful assessment of each patient)
Tacrolimus Trough levels were adjusted as 4–6 ng/dL.
Drugs targeting immune response regulation:
Interferons And Dexamethasone.
Dexamethasone in those receiving respiratory support (invasive mechanical ventilation or oxygen alone): resulted in lower 28-day mortality (3)
Drugs that preventing viral replicatation:
Paxlovid, remdesivir, molnupiravir, favipiravir, ribavirin, & Kaletra.
Remdesivir: The Adaptive COVID-19 Treatment Trial proved that remdesivir-treated patients had 31% faster time to recovery when compared to control (1)
Case series and a small RCT suggested better outcomes with interferon and high-dose steroids in conjunction with supportive care (2)
References
1) Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
2)Bitterman R, Kumar D. Respiratory Viruses in Solid Organ Transplant Recipients. Viruses. 2021 Oct 25;13(11):2146. doi: 10.3390/v13112146. PMID: 34834953; PMCID: PMC8622983.
3)RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
4)Samavat et al. COVID-19 in Kidney Transplantation Recipients, Iranian Journal of Kidney Diseases | Volume 14 | Number 3 | May 2020
5-Demir, E., Ucar, Z.A., Dheir, H. et al. COVID-19 in Kidney Transplant Recipients: A Multicenter Experience from the First Two Waves of Pandemic. BMC Nephrol 23, 183 (2022). https://doi.org/10.1186/s12882-022-02784-w.
6-Study of Scientific Board Republic of Turkey, Ministry of Health. COVID-19 (SARS-CoV-2 INFECTION) GUIDE. April 14th, 2020, Ankara, Turkey.
7-Semenzato L, Botton J, Drouin J, et al. Chronic diseases, health conditions and risk of COVID-19-related hospitalization and in-hospital mortality during the first wave of the epidemic in France: a cohort study of 66 million people. The Lancet Glob Health Regional Health – Europe. 2021; 8:100158. https://doi.org/10.1016/j.lanepe.2021.100158.
That is a fantastic reply that is very well-referenced. Typing whole sentence in bold or typing in capitals amounts to shouting.
This patient is 2 months post transplant and is on triple immunosuppression after receiving a kidney from a living donor. He has a history of Wegners granulomatosis
He has COVID 19 disease as evidenced by a positive PCR after having a productive cough
Based on his signs and symptoms, he has has mild COVID 19 disease as his vital signs are stable and his CXR is clear
He is in the early post-transplant phase
We should get more history to assess his rejection risk:
This is important as this will guide further treatment
The ideal treatment in patients who develop moderate to severe COVID 19 disease post transplant is to reduce the immunosuppression and to stop the antimetabolite and to continue with the CNI as the CNIs inhibit IL1 and IL6. This is always weighed against the risk of the patient developing acute rejection.
The use of antimetabolites in COVID 19 has been linked to poor outcomes in SOT recipients. However, whether stopping the antimetabolites during the COVID 19 infection improved outcomes remains unclear
Some authors have postulated that maintenance of immunosuppression will dampen the inflammatory cytokine storm seen in COVID 19 infections.
There was a reported higher risk of bacterial and fungal infections after using therapies for COVID 19 including dexamethasone and IL 6 inhibitors
The SOT patients who have COVID 19 infection are known to shed the virus longer than the general population. Therefore, these patients need to be careful after contracting COVID 19 as the risk of transmission remains higher even after 21 days. There is also a higher risk of relapse
For this patient, I would reduce the tacrolimus levels to between 8-12, maintain supportive care and manage the patient as an outpatient, and closely monitor the patient for developing acute rejection or progressing to develop severe disease
An Overview of COVID 19 in Solid Organ Transplantation. L. Bartelt, D. van Duin / Clinical Microbiology and Infection 28 (2022) 779e784
Your reply is rather limited. It does not address all the concerns.
I like that you would effect the following modification in immunosuppression: reduction of tacrolimus and stopping MMF for few days.
Typing whole sentence in bold or typing in capitals amounts to shouting.
How would you manage this case ?
Substantiate your answer :
This patient is known case of wegener granulomatosis present 2 month after kidney transplantation with productive cough which was tested positive for SARS-COV- 2 RNA with normal clinical examination and stable graft function ,his prograf level is 13.4ng/ml
Management of COVID-19 ;
This patient has mild covid 19 infection depending on the above mentioned data so no need for hospital admission. He needs a full blood count looking for lymphopenia,inflammatory markers ,graft functions .Home management with self isolation Adjustment of tacrolimus dose to therapeutic level MMF dose can be reduced to 250 mg bid and to be stopped if the patient is deteriorating .Advice the patient to follow oxygen saturation at home and to come immediately if desaturated or developed shortness of breath .
References;
Demir, E., Ucar, Z.A., Dheir, H. et al. COVID-19 in Kidney Transplant Recipients: A Multicenter Experience from the First Two Waves of Pandemic. BMC Nephrol 23, 183
(2022). https://doi.org/10.1186/s12882-022-02784-w.
Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
Your reply is rather limited. It does not address all the concerns.
I like that you would effect the following modification in immunosuppression: reduction of tacrolimus and stopping MMF for few days.
The index patient is a recent (2 month back) live donor renal transplant recipient with basic disease of granulomatous polyangiitis, on tacrolimus based triple drug immunosuppression, presenting with productive cough. Clinical examination is unremarkable, and SARS-CoV-2 test is positive.
The management of the index case involves:
a. Isolation of the patient.
b. In case there is no hypoxia and only cough without any tachypnea, patient can be isolated at home. Monitoring of temperature, respiratory rate and SpO2 can be done at home and the patient can remain in contact with the clinician via tele-medicine.
c. Mild to moderate illness (SpO2 >94% without requiring any supplemental oxygen) does not require anything other than symptomatic treatment (3). Those with high risk of progression (obesity, diabetes mellitus, hypertension, immunosuppressed patients) may be given high-titre COVID-19 convalescent plasma if within 8 days of onset of disease. Other options include 3 days of remdesivir (within 7 days of symptom onset), nirmatrelvir/ritonavir or molnupiravir (within 5 days of onset), or neutralizing monoclonal antibodies (within 7 days of onset). No role of hydroxychloroquine, azithromycin, lopinavir/ritonavir, dexamethasone, inhaled steroids, dexamethasone ivermectin, colchicine, and famotidine in such patients.
d. If the patient worsens and develops severe (SpO2 <94% on room air) or critical (end-organ dysfunction, requiring ventilatory support) illness, patient should be admitted in hospital. Dexamethasone 6 mg daily for 10 days should be given. 5 days of remdesivir treatment can be given to patients on supplemental oxygen (but not to patients on mechanical ventilation). Those who cannot be given steroids due to contraindication, should be given Baricitinib with remdesivir. In presence of elevated markers of systemic inflammation, use of Tocilizumab (or Sarilumab) is recommended (3).
e. Immunosuppression: In the index patient, MMF can be reduced to 250 mg twice a day. Antimetabolites should be stopped and tacrolimus doses to be adjusted as per trough (target 4-6) levels in case of severe or critical illness (3). We should be watchful for worsening of graft function/ rejection due to reduction in immunosuppression.
The index patient is having a mild to moderate COVID-19 disease (only symptom is productive cough, unremarkable clinical examination, clear chest x ray and stable graft function). He should be managed as outpatient, be kept in home isolation, managed symptomatically, with close self-monitoring via tele-consultation. In case of worsening symptoms, or fall in SpO2, patient should be hospitalized and managed with remdesivir for 3 days (200 mg on first day and then 100 mg daily) or for 5 days (if supplemental oxygen is required but not on ventilator or ECMO). MMF should be stopped and tacrolimus dose should be adjusted with target trough level of 6. If oxygen saturation falls to <94%, dexamethasone 6 mg daily for 10 days should also be started (4). Further worsening would require Tocilizumab (in presence of elevated inflammatory markers like IL-6). Due to early post-transplant period (2 months old), the risk of acute rejection should be kept in mind.
References:
That is a fantastic reply. I would not add to that except commenting that covalescent plasma has not been shown to be of proven benefit.
A case of renal transplant recipient from a living donor on triple maintenance therapy with stable kidney function ,he was a known as a case of Wegner granulomatosis presented 2 months post transplant with SARS COV 2 infection.
Management
The patient need to be evaluated regarding detailed medical history, his clinical exam is unremarkable .
His oxygen saturation and general condition need assessment to decide if he needs admission or home isolation with close follow up can be suitable
Investigations
include full basic lab as CBC with differential ,KFT ,LFT ,electrolytes ,urine analysis and culture ,sputum and blood culture , inflammatory markers as ferritin ,LDH and ddimer, crp ,Tac trough level,coagulation profile
Treatment
Isolation along with supportive care in the forum of good hydration and antipyretics if needed along with symptomatic treatment
US FDA authorized remdesivir administration as a treatment option for hospitalized COVID-19 patients given 200 mg intravenously on the first day followed by 100 mg intravenously daily.
If he deteriorated became oxygen dependent dexamethasone 6 mg can be added
The Recovery Collaborative Group has shown that dexamethasone benefits hospitalized patients receiving oxygen therapy
For immunosuppression as the graft function is stable ,MMF can be suspended and tacrolimus can be continued with reducing the dose and monitoring of trough levels to prevent allograft rejection and CNI toxicity
If patient deteriorated with cytokine storm signs Toclizumab 400 mg IV once
Reference
– Elhadedya M A , Mariea Y ,Halawa A .COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence.Nephron 2021;145:192–198
-Ravi Raju Tatapudi, Venkateswara Rao Kopparti, Anusha Poosapati, Srinivas Metta, Atchyutha Rao Gongada, Balakrishna Vedulla, “SARS-CoV-2 Infection in Kidney Transplant Recipients: A Single-Centre Study of 20 Cases from India”, International Journal of Nephrology, vol. 2021, Article ID 2243095, 7 pages, 2021.
I like your clinical approach.
I like the following modification in immunosuppression: reduction of tacrolimus and stopping MMF for few days. I am not sure if this patient would really need anti-COVID drug.
– The index case 2 months post-KT, confirmed to have COVID-19 infection, and mild clinical presentation.
– This patient can be managed at home to reduce the risk of acquiring nosocomial infection.
– At any point if symptoms progress, consider admission.
– Need to ensure easy hospital access and communication with transplant center, otherwise, will be managed as inpatient.
– Ensure normal O2 saturation.
Work up:
– CBC; VBG, CRP, ESR, ferritin, coagulation profile.
– LFT and Kidney function test.
– Tacrolimus level monitoring.
Treatment;
– Supportive management; ensure good hydration, control fever if present.
– Management of immunosuppressive is challenge need to balance with rejection risk.
– Hold antimetabolite, especially in lymphopenic patients (absolute lymphocyte count <700 cells/mL)
– CNI inhibit IL-1 and IL-6 which contribute to the severity of covid infection.
– However, the level is 13 high need to be reduced to 8-10.
– If infection is sever and progressive we can reduce CNI through level or complete stopping while increasing steroids does.
– Monitor graft function closely.
– Dexamethasone if patient require respiratory support, reduce mortality.
– All antiviral therapy are investigational, Not required in our index case.
– Consider drug-drug interaction if any new treatment used.
* Remdesivir; can be used if duration of symptoms < 7 days, RCT showed 87% reduction in risk of hospitalization or death among high-risk, non-hospitalized patients who received a 3-day course of remdesivir compared to those who received the placebo.
*Nirmatrelvir-ritonavir; for emergency use in mild to moderate symptomatic COVID-19 in patients at high risk for progression,
-Advice on COVID-19 vaccination after recovery from acute infection
References:
Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
Bitterman R, Kumar D. Respiratory Viruses in Solid Organ Transplant Recipients. Viruses. 2021 Oct 25;13(11):2146. doi: 10.3390/v13112146. PMID: 34834953; PMCID: PMC8622983.
RECOVERY Collaborative Group; Horby P, et al. Dexamethasone in Hospitalized Patients with Covid-19. N Engl J Med. 2021 Feb 25;384(8):693-704. doi: 10.1056/NEJMoa2021436. Epub 2020 Jul 17. PMID: 32678530; PMCID: PMC7383595.
Brady, D.K., Gurijala, A.R., Huang, L., Hussain, A.A., Lingan, A.L., Pembridge, O.G., Ratangee, B.A., Sealy, T.T., Vallone, K.T. and Clements, T.P. (2022), A guide to COVID-19 antiviral therapeutics: a summary and perspective of the antiviral weapons against SARS-CoV-2 infection. FEBS J. https://doi.org/10.1111/febs.16662
Gottlieb RL, Vaca CE, Paredes R, Mera J, Webb BJ, Perez G, Oguchi G, Ryan P, Nielsen BU, Brown M, Hidalgo A, Sachdeva Y, Mittal S, Osiyemi O, Skarbinski J, Juneja K, Hyland RH, Osinusi A, Chen S, Camus G, Abdelghany M, Davies S, Behenna-Renton N, Duff F, Marty FM, Katz MJ, Ginde AA, Brown SM, Schiffer JT, Hill JA; GS-US-540-9012 (PINETREE) Investigators. Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients. N Engl J Med. 2022 Jan 27;386(4):305-315. doi: 10.1056/NEJMoa2116846. Epub 2021 Dec 22. PMID: 34937145; PMCID: PMC8757570.
I like your well-referenced clinical approach. I like the following modification in immunosuppression: reduction of tacrolimus and stopping MMF for few days.
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 a productive cough and 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.
====================================================================
How would you manage this case?
History
Tacrolimus goals and achieved levels (average trough level) at months 1, 4, and 12.
10-12 mg/dl
8-10 mg /dl
6-8 mg/dl
====================================================================
====================================================================
Reference
I like your clinical approach.
I like the following modification in immunosuppression: reduction of tacrolimus and stopping MMF for few days. Typing whole sentence in bold or typing in capitals amounts to shouting.
How would you manage this case?
In general, Transplant patients are at a high risk of infection due to multiple risk factors, including immunosuppression, underlying CKD, and associated comorbidities including HTN and DM. Some studies reported that hypertensive and diabetic patients have a double-fold risk of infection, while COPD patients have a 5-fold risk.In view of COVID 19 era,transplant patients needs a special care if they are infected.
In ur case scenario of stable transplant patient with stable graft function with mild COVID infection .He has history of vasculitis which can be considered as a risk factor ,the management will be as following:
-Isolation
-Plenty amount of fluids
-Symptomatic treatment of fever if there.
-oral antibiotics to guard against secondary bacterial infections
-Daily CBC,renal function,CRP,procalcitonin,ferritin level and ABGs.some studies showed low lymphocyte/white blood cell ratio both on admission and during hospitalization had fatal outcomes.
-Repeat chest x ray(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).
-Immunosuppression: Hold MMF,switch oral steroids to IV steroids ,reduce tacrolimus dose in settings of high trough level targeting 5-8 ng/ml. Managing immunosuppression in kidney transplant recipients depends on the age, the severity of infection, the post-transplant duration, any other associated comorbidity, tissue mismatch, and any episodes of rejection should be considered in hold or reduce the immunosuppression and the treatment should be individualized based on the careful assessment of each patient.
-Close monitoring of oxygen saturation ,UOP and hemodynamics.
-From experience of COVID patients they have unpredictable curse.
The recent studies after COVID era 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.
References:
1- Cheng Y, Luo R, Wang K, Zhang M, Wang Z, Dong L, et al. Kidney disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020 May;97(5):829–38
2- Chu KH, Tsang WK, Tang CS, Lam MF, Lai FM, To KF, et al. Acute renal impairment in coronavirus-associated severe acute respiratory syndrome. Kidney Int. 2005 Feb;67(2): 698–705
I like your clinical approach. I like the following modification in immunosuppression: reduction of tacrolimus and stopping MMF for few days.
Immunosuppression is one of many risk factors that puts transplant recipients at a greater risk of infection.
MANAGMENT
Daily differential complete blood count (CBC) with an emphasis on the total lymphocyte count trend
Basic metabolic panel
Hepatic panel
C-reactive protein (CRP)
Lactate dehydrogenase
Prothrombin time (PT)/partial thromboplastin time (PTT)/fibrinogen/D-dimer
measure O2 saturation
Features suggest a severe illness:
Hyperoxia (oxygen saturation of less than 94% in room air)
Requirement for ventilator support or oxygenation
FURTHER MANAGMENT
Level of TAC. Need to be recheck and need to be adjust accordingly, it seems to be high as patient might be on antiviral drugs,
Graft function monitoring and may require graft biopsy to check rejection.
Only moderate to severe cases call for reducing immunosuppression.
Given that the patient’s symptoms are not severe, there is no need to increase the steroid dosage for the existing patients.
If the following criteria are met, specific antiviral medication (oral nimatrelvir/ritonavir or intravenous remdisvir) is appropriate in mild to moderate cases.
1-Patients run the danger of their illness progressing to a severe stage, including;
patients with compromised immunity (SOT, HIV)
Individuals with various comorbid conditions, such as cancer, diabetes mellitus (DM), smoking, , tuberculosis (TB), cerebrovascular illness,
Patients over the age of 65 Patients
2-Patients who are more than 7 days past the onset are only treated with supportive measures. The duration from symptom onset is 5 days for nimatrelvir/ritonavir and 7 days for remdisvir.
Tacrolimus dose reduction because the trough level is already high, begin antiviral medication that may raise CNI levels even further, and monitor those levels.
COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence
Muhammed Ahmed Elhadedy ,Yazin Marie Ahmed Halawa
US FDA. Remdesivir letter of EUA. https://www.fda.gov/media/137564/download (Accessed on January 24, 2022).
Predictors of COVID-19 severity: A literature review
Benjamin Gallo Marin , Ghazal Aghagoli , Katya Lavine , Lanbo Yang , Emily J Siff , Silvia S Chiang , Thais P Salazar-Mather , Luba Dumenco , Michael C Savaria , Su N Aung , Timothy Flanigan Ian C Michelow
I like your clinical approach.
I like the following modification in immunosuppression: reduction of tacrolimus. But you have not mentioned stopping MMF for few days. I am not sure if this patient would really need anti-COVID drug.
The management of Covid-19 in post renal transplantation nearly same as general population despite some differences such as higher rate of hospitalization, AKI
, longer viral shedding but mortality nearly same
this case scenario….mild and patient in very critical early post operative period, so require close monitoring
investigations as other Covid-19 cases as per centers
Treatment as per local Covid-19 centers; in mild cases supportive treatment
adjustment of drugs and stop antimetabolite medications
Your reply is rather limited. It does not address all the concerns.
I like to believe that you would effect the following modification in immunosuppression: reduction of tacrolimus and stopping MMF for few days.
– I will measure O2 saturation (O2 sat ≤ 92% is considered severe) and perform Borg scale after 6 minutes exercise to better asses the severity of dyspnea and the patient will inform us about the severity of dyspnea (mild, moderate or severe)
– CT is not indicated once the patient ha mild symptoms with normal O2 saturation and normal CXR imaging
– Reduction of immunosuppression is indicated only in moderate to severe cases and is not indicated in the current mild case presenting with just productive cough, but tacrolimus level is high in the current case, so, I will reduce the dose to attain a level between 7-10 ng/ml in the first 3 months after transplantation
– No need to increase the dose of steroid in the current patients since the patient has non severe symptoms
– Specific antiviral therapy (oral nimatrelvir/ritonavir or intravenous remdisvir) is indicated in mild to moderate cases if the followings are met
1- Duration from symptom onset is ≤5 days for nimatrelvir/ritonavir , or ≤ 7 days for remdisvir (patients who are > 7 days from the onset are treated with supportive measures only)
2- Patients are at risk of progression to severe disease including:
Patients who are immunosuppressed (SOT, HIV)Patients with multiple comorbidities like cancer, DM, smoking, pregnancy , TB, cerebrovascular disease, bronchial asthma, COPD, renal failure, heart failure and liver failurePatients >65 years oldPatients > 50 years and unvaccinated
The choice between the 2 drugs depends on the followings
1- Duration elapsed from symptom onset
If within 5 days from the symptom onset both can be given with preference of nimatrelvir/ritonavir (nimatrelvir 300 mg and ritonavir 100 mg twice daily for 5 days)If in the 6th or 7th day after onset of symptoms remdisvir is preferred 2- Renal function tests
In patients with GFR 60 both can be given with preference of nimatrelvir/ritonavir (nimatrelvir 300 mg and ritonavir 100 mg twice daily for 5 days)In pateitns with GFR between 30-60 both can be given with preference of nimatrelvir/ritonavir (nimatrelvir 150 mg and ritonavir 100 mg twice daily for 5 days)In patietns with GFR < 30 remdisvir is preferred (200 mg IV in the first day then 100 mg daily for another 2 days) since nimatrelvir/ritonavir is contraindicated3- Liver function tests
In patients with advanced liver faliuer child C, remdisvir is preferred In patients without advanced liver failure both can be given with preference of nimatrelvir/ritonavir (nimatrelvir 300 mg and ritonavir 100 mg twice daily for 5 days)4- Drug-drug interactions
Nimatrelvir/ritonavir are potent CYP3A inhibitors and have several drug-drug interactions so we have to check the drugs given concomitantly and if there is contraindication for coadmisntarationand the other drug is vital and can not be withdrawn for the duration of therapy and 3 days after sdiscontinuation, remdisvir will be preferred In the setting of transplantation, nimatrelvir/ritonavir increase the trough level of CNI and thus the dose of CNI should be reduced once we introduce this drugs.So … in the current
I will asses the severity of infection using 6 min exercise and O2 saturationI will reduce the dose of tacrolimus markedly since the trough level is already high and I will start antiviral therapy that may further increase the level of CNI and follow up the level every 3 days till stopping the antiviral therapy and stabilization of the levelI will start oral nimatrelvir/ritonavir for 5 days
I like your clinical approach.
I like the following modification in immunosuppression: reduction of tacrolimus. But you have not mentioned stopping MMF for few days. I am not sure if this patient would really need anti-COVID drug.
Your reply is rather limited. It does not address all the concerns.
I like to believe that you would effect the following modification in immunosuppression: reduction of tacrolimus and stopping MMF for few days.
Management:
References:
A.How would you manage this case?
References
Thankyou.
Wlcm prof
How would you manage this case?
This patient:
o Had a history of Wegner’s granulomatosis
o Presented 2 months after transplantation only with productive cough, no other symptoms
o Clinical examination was unremarkable
o Normal kidney function and clear chest-x-ray
o High tacrolimus trough level
o And confirmed to be COVID-19 (positive SARS-CoV-2 RNA)
This transplant patient is at a high risk of infection due to:
1. Immunosuppression
2. Underlying CKD
Management of COVID-19 (mild infection):
o CBC (lymphopenia), CRP, s.ferritin, and IL-6
o Outpatient management with self-isolation and advice to drink a lot of fluids
o Discontinue MMF
o Reduction of tacrolimus dose
o Monitoring of renal functions and tacrolimus level
o Return back to the transplant unit if any new symptoms appear
References
1. Elhadedy MA, Marie Y, Halawa A. COVID-19 in Renal Transplant Recipients: Case Series and a Brief Review of Current Evidence. Nephron. 2021;145(2):192-198. doi: 10.1159/000512329. Epub 2020 Dec 8. PMID: 33291120; PMCID: PMC7801980.
2. Demir, E., Ucar, Z.A., Dheir, H. et al. COVID-19 in Kidney Transplant Recipients: A Multicenter Experience from the First Two Waves of Pandemic. BMC Nephrol 23, 183 (2022). https://doi.org/10.1186/s12882-022-02784-w
Thankyou
This current case is ( S/P LRRTX in 2/2020 with SARS-COV-2 RNA +ve ):
Indications for hospitalization;
-This patient is COVID-19 with mild disease that does not warrant hospital-level care;
-This patient need self-isolate at home and recover at home is preferred.
Evaluation with further investigation;
-Complete blood count (CBC) with differential, with a focus on the total lymphocyte count trend, daily,
-Basic metabolic panel daily
-Hepatic panel every other day (or daily if elevated or in the intensive care unit)
-C-reactive protein (CRP) – Ferritin
-Lactate dehydrogenase
-Prothrombin time (PT)/partial thromboplastin time (PTT)/fibrinogen/D-dimer
-Troponin
-Electrocardiogram (ECG), with at least one repeat test after starting any QTc-prolonging agent
Thromboprophylaxis; if high risk for venous thromboembolism.
Antipyretics; acetaminophen for fever reduction rather than non-steroidal anti-inflammatory drugs (NSAIDs).
Continuing chronic medications; Patient who is on an ACE inhibitor or ARB for another indication should not stop his medications
-Continue statins in hospitalized patients with COVID-19 who are already taking them, also continue aspirin unless there is concern for bleeding risk.
Monitoring Po2 Sat. for assessment for Oxygen requirement; requested ABG , (target Po2 sat. ≥ 94%).
Management of hypoxemia; Patients with severe disease often need respiratory support.
Infection control; is an essential component of management of patients with suspected or documented COVID-19.
Treatment this case with mild severity;
-Supportive management with good hydration,
-Stop Mycophenolate mofetil and continue CNI and steroid,
-Adjustment of Tac. Trough to ( 4–6 ng/dL) , stop one or two doses till level decrease within the target range.
-If worsening and increase severity (required ITU), will stop CNI and increase the steroid dose to a stress dose and shifting to IV.
-COVID 19 treatment; ( by Pulmonology review using medications such as (hydroxychloroquine, azithromycin , Tocilizumab and others) & keep in mind drug-drug interaction.
-Strict monitoring for Graft function tests , FK level.
References;
1-D. K. Brady et al. A guide to COVID-19 antiviral therapeutics: a summary and perspective of the antiviral weapons against SARS-CoV-2 infection, The FEBS Journal (2022) Federation of European Biochemical Societies. doi: 10.1111/ febs. 16662.
2-Demir, E., Ucar, Z.A., Dheir, H. et al. COVID-19 in Kidney Transplant Recipients: A Multicenter Experience from the First Two Waves of Pandemic. BMC Nephrol 23, 183 (2022).
Thankyou
Patient had history of COVID-19 positive
need evaluation to check oxygen saturation
ABG
CBC for lymphopenia/ ESR/ CRP/ d. dimmer / procalcitonin level and LDH, LFT
COVID-19 PCR and igG, IgM, INR
CT chest
Management
Good hydration
Antiviral therapy, anticoagulant, intravenous immunoglobulin, and tocilizumab to be considered
reduce dose of tacrolimus to reach target level between (5-7), stop MMF and intravenous dexamthazone
Is this a moderate case or severe and needs admission with respective treatment for each.
How would you manage this case?
The patient is positive for COVID but has mild symptoms. I will request the CBC, procalcitonin, CRP, LDH, renal function, liver function, coagulation profile, and ferritin.
The treatment will depend on the lab results and the clinical manifestations.
mild cases like this one with normal inflammatory markers: reduce tacrolimus (13 is high) and reduce MMF to 250 mg bid and close observation at home for (fever, diarrhea, and SOB).
If any deterioration, the patient should be admitted to the hospital and stop MMF and keep the tac level 3-5
Hospitalized individuals with mild to severe, symptomatic COVID-19 may benefit from the same treatments as non-hospitalized patients. A large randomized controlled study indicated that a brief course of dexamethasone (6 mg daily for up to 10 days) enhanced survival in hospitalized severe COVID-19 patients who were mechanically ventilated or needed supplementary oxygen.
Tocilizumab or baricitinib with dexamethasone is indicated for severe or critical COVID-Immunosuppressive drugs including dexamethasone, tocilizumab, and baricitinib should be watched for secondary infections.
COVID-19-infected transplant recipients should get therapeutic anticoagulation like other hospitalized patients. COVID-19 patients with platelet counts <50,000 cells/μL should not get therapeutic anticoagulation. Physicians treating thrombocytopenia should follow hospital anticoagulation procedures.
In hospitalized COVID-19 patients, the Panel recommends remdesivir, dexamethasone, tocilizumab, baricitinib, and anticoagulation.
Interactions
Calcineurin inhibitors (cyclosporine, tacrolimus) and mTOR inhibitors (everolimus, sirolimus) used to prevent allograft rejection have limited therapeutic indices. Drugs that inhibit or stimulate cytochrome P450 (CYP) enzymes or P-glycoprotein may cause clinically significant
drug-drug interactions, requiring therapeutic drug monitoring and toxicity or rejection assessment. For mild to severe COVID-19 in nonhospitalized individuals at risk of disease progression, ritonavir-boosted nirmatrelvir (Paxlovid) is recommended for 5 days. Due to ritonavir, this regimen may cause complicated drug-drug interactions with concurrent medicines.
Ritonavir, a potent CYP3A inhibitor, boosts nirmatrelvir to a SARS-CoV-2-effective concentration. Ritonavir may also boost calcineurin and mTOR inhibitor concentrations during therapy and for three days thereafter. Increased medication concentrations may cause significant and even fatal drug toxicities.
RECOVERY Collaborative Group. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2021;397(10285):1637-1645. Available at:
Thankyou correct plan.
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 a productive cough and 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.
How would you manage this case?
A case of post Kidney transplant with SARS-COV-2 RNA positive and productive cough with history of Wegner’s granulomatosis.
We should classify our patient according to his clinical manifestation:
1-Asymptomatic patients and patients with mild disease (oxygen saturation above 93%, no lung involvement on chest computed tomography) were followed up in the outpatient clinic weekly.
2-Patients with moderate disease (oxygen saturation above 90%, respiratory rate under 30 breaths/min) were hospitalized in the first wave of the pandemic and followed up in the outpatient clinic in the later period because of hospital overcrowding.
3-Hospitalization were severe disease (oxygen saturation under 90%, respiratory rate above 30 breaths/min), cytokine storm (persistent fever, high or increasing CRP, ferritin, and D-dimer, abnormalities in liver function tests, hypofibrinogenemia with cytopenia in the forms of lymphopenia and thrombocytopenia).
Our patient should be treated with supportive treatment and treated as outpatient(by telemedicine), no need for hospitalization.(group 1 ).
= A protocol was used to :manage immunosuppression, antiviral, and cytokine‐targeted therapy
=Stop Mycophenolate mofetil and continue CNI and steroid , if worsening and our patient being in sever condition , will stop CNI and increase the steroid dose and shifting to IV.
=Trough levels were adjusted as 4–6 ng/dL for tacrolimus( here we need to decrease tacrolimus dose).
=COVID 19 treatment by chest physician using medications such as (hydroxychloroquine, azithromycin Tocilizumab and others) should bear in mind drug-drug interaction.
=Strict follow up for Renal function test, urine PCR and tacrolimus level.
References:
1-2-Demir, E., Ucar, Z.A., Dheir, H. et al. COVID-19 in Kidney Transplant Recipients: A Multicenter Experience from the First Two Waves of Pandemic. BMC Nephrol 23, 183 (2022). https://doi.org/10.1186/s12882-022-02784-w.
2-Study of Scientific Board Republic of Turkey, Ministry of Health. COVID-19 (SARS-CoV-2 INFECTION) GUIDE. April 14th, 2020, Ankara, Turkey.
3-Semenzato L, Botton J, Drouin J, et al. Chronic diseases, health conditions and risk of COVID-19-related hospitalization and in-hospital mortality during the first wave of the epidemic in France: a cohort study of 66 million people. The Lancet Glob Health Regional Health – Europe. 2021;8:100158. https://doi.org/10.1016/j.lanepe.2021.100158.
Which category did you place this index case?
You put him in group one and suggested cytokine control antivirals?
you correctly reduced TAC and dc. MMF.
He can be managed by Tele medicine.
Thanks professor :Dawlat.
1-Our patient should be categorized by clinical assessment and according to O2 saturation (group 1) and group 2 in the second wave, no hospitalized.
2-Regarding cytokine control therapy is considered apart of the general protocol and not specific to our case.
3-Tele medicine enables video or phone appointments between a patient and their health care practitioner to decrease load on health care system and decrease rate of infection
How would you manage this case?
Substantiate your answer.
Non-contrast CT chest:
Laboratory tests:
Findings linked to higher disease severity &/or fatality include:
Treatment of mild disease include:
Antiviral treatments:
Antiviral categories
Viral entry targeted antivirals:
Viral replication targeted antivirals:
Protein trafficking and post-translational modifications targeted antivirals:
References
Perfect, Will you observe him as an outpatient or inpatient?
Thank you, dear Prof. Ahmed
The patient is stable & not in any acute distress. Therefore, I will observe him in an outpatient setting. Arrangements for inpatient or specialized center admission should be made clear to the patient in case of any deterioration or desaturation occurs.
1. I would perform a non-contrast-enhanced CT scan of the chest to assess the progression of lung disease
2. I would request arterial blood gases to assess how the pulmonary gas exchange is doing since COVID-19 can occur with silent hypoxemia
3. I would not start Nimetravir + Ritonavir (Paxlovid) due to prohibitive drug interactions with immunosuppressive drugs and which could lead to graft dysfunction. Oral molnupiravir is an option for patients who are not yet on oxygen therapy.
Remdesivir (associated or not with Baricitinib) can be performed. If there is no progression and need for oxygen therapy, do it for three days, if there is evolution, expand to five days and associate corticosteroids.
4. Decreasing immunosuppression is a necessity, as measuring serum levels and considering drug interactions.
5. Clinical follow-up in the hospital with respiratory isolation with negative pressure to assess respiratory progression.
6. Subsequent immunization following local protocols
Thanks, Riham Isaac
Professor, immunosuppressed patients are at high risk for complications. The patient is currently doing well clinically, which would indicate the use of Remdesevir on a three-day regimen to stop disease progression (Gottlieb et al).
Here in Brazil we have done it for patients undergoing bone marrow transplants or using antiplasmacytic drugs.
With the withdrawal of Evusheld from the market and the difficulty of entry of Paxlovid and Molpurinavir, Remdesivir became the necessary strategy (and the only one).
Paxlovid has many interactions with immunosuppressants, making Molnupiravir the best drug, but with much lower efficacy compared to the others.
With the difficulty in accessing specialized care, he would remain hospitalized until he defined the necessary care and monitored the evolution of the lung disease.
Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients.
Gottlieb RL, Vaca CE, Paredes R, Mera J, Webb BJ, Perez G, Oguchi G, Ryan P, Nielsen BU, Brown M, Hidalgo A, Sachdeva Y, Mittal S, Osiyemi O, Skarbinski J, Juneja K, Hyland RH, Osinusi A, Chen S, Camus G, Abdelghany M, Davies S, Behenna-Renton N, Duff F, Marty FM, Katz MJ, Ginde AA, Brown SM, Schiffer JT, Hill JA; GS-US-540-9012 (PINETREE) Investigators.
N Engl J Med. 2022 Jan 27;386(4):305-315. doi: 10.1056/NEJMoa2116846. Epub 2021 Dec 22. PMID: 34937145
How will you manage this case?
This is a case of confirmed COVID-19 with mild respiratory symptoms and good kidney function. This could have been managed as an outpatient case, while the patient must be well-informed of deteriorating signs like fever and persistent reduction in saturation.
However, because of risk factors like CKD/ transplant, and background etiological cause of CKD (Wegener granulomatosis), I will admit and manage as follows
References
Thanks, Isaac
I agree, he does not need hospitalisation and can be treated as an outpatient.
Does he need to be treated with Remidisivir and big doses of steroids as you mentioned or just watch and wait?
What do you think about the tac level?
Thank you prof Halawa for your response
He will definitely not need Remdesivir because of mild symptoms now, except if he deteriorated
The steroid dose will not exceed 6mg OD for the mild case
The Tacrolimus trough level will be kept at 4-6ng/ml with close monitoring of kidney function
management:
1- hospitalization
2-good hydration
3-stop MMF
4-continue CNI and steroid
5-follow up graft function
6-CT chest
6-follow up CXR
Thanks, Riham