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Table of Contents
ORIGINAL ARTICLE
Year : 2022  |  Volume : 16  |  Issue : 2  |  Page : 216-219

Remdesivir in renal transplant patients with coronavirus disease 2019: An observational study


1 Division of Nephrology, Superspecialty Hospital, Government Medical College, Srinagar, Jammu and Kashmir, India
2 Division of Pathology, Government Medical College, Srinagar, Jammu and Kashmir, India
3 Division of Nephrology, ASCOMS Hospital, Jammu, Jammu and Kashmir, India
4 Department of Medicine, Government Medical College, Baramula, Jammu and Kashmir, India
5 Department of Pharmacy Practice, Nova College of Pharmaceutical Education and Research, Hyderabad, Telangana, India
6 Flushing Hospital Medical Center, New York, USA

Date of Submission25-May-2021
Date of Acceptance29-Jul-2021
Date of Web Publication30-Jun-2022

Correspondence Address:
Dr. Muzamil Latief
Division of Nephrology, Superspecialty Hospital, Government Medical College, Srinagar - 190 010, Jammu and Kashmir
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijot.ijot_54_21

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  Abstract 


Introduction: Remdesivir has shown broad-spectrum antiviral activity. This drug is approved by the Food and Drug Administration for coronavirus disease 2019 (COVID-19) management. Other than a few case series and case reports, not much information is available on its use in kidney transplant recipients (KTRs). Materials and Methods: We describe our experience of seven KTRs with COVID-19. All the patients were hypoxemic. High-resolution computed tomography (CT) chest was done in all the patients. Injection remdesivir 200 mg on day 1 followed by 100 mg daily was given for a maximum of 5 days irrespective of estimated glomerular filtration rate (eGFR). Observations and Results: Mean age of patients was 46.28 ± 10.41 years and one patient was female. Mean CT severity score was 15. In our study, 2 patients who required mechanical ventilation expired. None of our patient had worsening of acute kidney injury (AKI) or new-onset AKI after institution of remdesivir. Discussion: Optimal management for this patient population remains unknown, therefore, treatment of COVID-19 in KTRs varies from center to center. The studies on remdesivir use in KTRs with COVID-19 are not extensive. Our series does indicate safety of remdesivir in KTRs. Conclusion: We observed that remdesivir can be used in KTRs with COVID-19 with hypoxemia irrespective of eGFR. We suggest that large-scale studies should be done to substantiate these findings.

Keywords: Coronavirus disease 2019, kidney transplant recipient, remdesivir


How to cite this article:
Latief M, Abbas F, Iqbal M, Hassan Z, Goud L N, Shafi O. Remdesivir in renal transplant patients with coronavirus disease 2019: An observational study. Indian J Transplant 2022;16:216-9

How to cite this URL:
Latief M, Abbas F, Iqbal M, Hassan Z, Goud L N, Shafi O. Remdesivir in renal transplant patients with coronavirus disease 2019: An observational study. Indian J Transplant [serial online] 2022 [cited 2022 Aug 15];16:216-9. Available from: https://www.ijtonline.in/text.asp?2022/16/2/216/349364




  Introduction Top


There is a lack of standardized and effective treatments for coronavirus disease 2019 (COVID-19) and it has lead the scientific community world over to look at several drugs that have been used in other conditions including antiviral drug remdesivir (RDV).[1] Remdesivir is an adenosine analog, developed to treat Ebola virus disease and has shown broad-spectrum antiviral activity.[2],[3] Triphosphate metabolite of remdesivir is incorporated into nascent viral RNA chains leading to inhibition of the RNA polymerase and results in premature termination of the RNA transcription.[4],[5] This drug is approved by the Food and Drug Administration for COVID-19 management. Remdesivir and chloroquine have been demonstrated to be effective in the control of 2019-nCoV infection in vitro.[6] There are concerns about remdesivir toxicity in patients with kidney disease, however, data from randomized controlled trials in COVID-19 patients with normal kidney function have not demonstrated an increased risk of renal adverse events.[7] Many centers have removed estimated glomerular filtration rate (eGFR) restrictions on the use of RDV, although safety data is yet scarce and more evidence is needed in this regard. Other than a few case series and reports, not much information is available on its use in kidney transplant recipients (KTRs).


  Materials and Methods Top


We describe our experience of remdesivir use in COVID-19 infection in KTRs. In this series, we report 7 KTRs, of whom 2 were deceased donor renal transplant recipients and 5 were living-related renal transplant recipients. All our patients had COVID-19 pneumonia and 3 of the patients had acute kidney injury (AKI). Our protocol was injection remdesivir 200 mg on day 1 followed by 100 mg daily for a maximum of 5 days. Antiproliferative agent (Mycophenolate Mofetil or Mycophenolate Sodium) was stopped on presentation to hospital in patients who were hypoxemic as per our protocol. All our patients were on prednisolone on presentation, and the dose was doubled in 5 patients whereas 2 patients who required mechanical ventilation were given injection methylprednisolone at a dose of 120 mg daily in two divided doses. Calcineurin inhibitor dosage was kept the same in 5 patients and discontinued in the patients on mechanical ventilation.

Statistical analysis

Statistical analyses were conducted using Statistical product and service solutions. Quantitative variables were expressed as mean ± standard deviation.

Patient consent

The patient consent has been taken for participation in the study and for publication of clinical details and images. Patients understand that the names and initials would not be published, and all standard protocols will be followed to conceal their identity.

Ethics statement

This study received ethical approval with IEC no. GM06/2021. The study was performed according to the guidelines in Declaration of Helsinki.


  Observations and Results Top


Mean age of our patients was 46.28 ± 10.41 years and only one patient was female. Mean computed tomography (CT) severity score was 15. The eGFR range in our series was 22–92 ml/min/1.73 m2. The clinical presentation, management, and outcome are shown in [Table 1] and [Table 2]. All the patients were on oxygen support and among these 2 patients who required mechanical ventilation expired. One of our patients had massive upper gastrointestinal bleeding requiring multiple transfusions and was on mechanical ventilation and expired on day 4 of hospital stay. This patient had AKI as well. None of the patients had worsening of kidney function after institution of RDV or required dialysis support. Mild elevation of liver enzymes (<2 times the upper limit of normal) was seen in all our patients. In our series, 5 patients who survived are doing well on follow-up and have resumed their baseline immunosuppression at 2-month postinfection with detectable IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-Cov2).
Table 1: Parameters of patients at presentation to hospitals

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Table 2: Clinical profile and outcome of patients

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  Discussion Top


Immunocompromised patients including those on immunosuppressive drugs following organ transplantation are considered high risk for severe disease from SARS-CoV-2.[8] So far, little data is available concerning the risk, clinical presentation, and prognosis of COVID-19 in KTRs.[9] Optimal management for this patient population is unknown, resulting in treatment of COVID-19 in KTRs being largely done on case-to-case basis. In a study which included 47 solid organ transplant (SOT) recipients, transplant status was not associated with increased mortality.[10] On the contrary, some studies have pointed out worse outcomes in these patients.[11],[12] In vitro studies demonstrated that remdesivir inhibits SARS-CoV-2.[6] Further RDV was also shown to result in inhibition of SARS-CoV-2 replication in human bronchial epithelial cells.[13],[14] There are no known drug interactions between RDV and any of the commonly used immunosuppressive drugs used in transplant recipients.[7],[15],[16] A general agreement is building that the potential benefits of RDV outweigh the potential risks of using remdesivir in SOT recipients with COVID-19. Many mutations, in particular involving the viral RdRp enzyme, could lead to remdesivir resistance. In a study, induced mutations in a murine hepatitis virus resulted in resistance to RDV.[17],[18] Whether a such kind of mutation will happen under natural conditions in SARS-CoV-2 is unclear yet, but if it did occur, then the virus would become resistant to RDV. Prolonged viral shedding due to immunosuppression could result in resistance among SOT patients. In many KTRs with COVID-19 particularly with mild illness, supportive measures, alteration in immunosuppressive medication, and careful monitoring are all that are needed as reported in some case series.[19],[20],[21],[22] The studies on remdesivir use in kidney tansplant patients with COVID-19 are not extensive so therefore studies should be encouraged to provide substantial data on remdesivir use in these patients. Our series does indicate safety of remdesivir in kidney transplant patients but given the small number of patients, it is difficult to draw conclusions. Similarly, studies looking at the alteration in immunosuppressive drugs in KTRs infected with SARS-CoV-2 are needed because as of now, the data are largely based on case series and reports.[21],[22]


  Conclusion Top


We conclude that remdesivir can be safely used in renal transplant patients with COVID-19 with hypoxemia even in patients who had AKI on presentation. We suggest that large-scale studies should be done to further study the role and safety of remdesivir use in renal transplant patients with COVID-19 and hypoxemia.

Limitations

Our study is based on small series of patients, and therefore, large studies are needed to substantiate our findings. We did not have a comparison group of KTRs who had COVID-19 with hypoxemia that did not receive remdesivir.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 2020;30:269-71.  Back to cited text no. 6
    
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Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al. Remdesivir in adults with severe COVID-19: A randomised, double-blind, placebo-controlled, multicentre trial. Lancet 2020;395:1569-78.  Back to cited text no. 7
    
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Johnson M, Belfer JJ, Peterson GR, Boelkins MR, Dumkow LE. Managing COVID-19 in renal transplant recipients: A review of recent literature and case supporting corticosteroid-sparing Immunosuppression. Pharmacotherapy 2020;40:517-24.  Back to cited text no. 8
    
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Chaudhry ZS, Williams JD, Vahia A, Fadel R, Acosta TP, Prashar R, et al. Clinical characteristics and outcomes of COVID-19 in solid organ transplant recipients: A case-control study. Am J Transplant 2020;20:3051-60.  Back to cited text no. 10
    
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Williamson BN, Feldmann F, Schwarz B, Meade-White K, Porter DP, Schulz J, et al. Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2. bioRxiv 2020;585:273-6.  Back to cited text no. 13
    
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Pizzorno A, Padey B, Julien T, Trouillet-Assant S, Traversier A, Errazuriz-Cerda E, et al. Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia. Cell Rep Med 2020;1:100059.  Back to cited text no. 14
    
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El Kassas M, Alboraie M, Al Balakosy A, Abdeen N, Afify S, Abdalgaber M, et al. Liver transplantation in the era of COVID-19. Arab J Gastroenterol 2020;21:69-75.  Back to cited text no. 15
    
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Shannon A, Le NT, Selisko B, Eydoux C, Alvarez K, Guillemot JC, et al. Remdesivir and SARS-CoV-2: Structural requirements at both nsp12 RdRp and nsp14 Exonuclease active-sites. Antiviral Res 2020;178:104793.  Back to cited text no. 17
    
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Guillen E, Pineiro GJ, Revuelta I, Rodriguez D, Bodro M, Moreno A, et al. Case report of COVID-19 in a kidney transplant recipient: Does immunosuppression alter the clinical presentation? Am J Transplant 2020;20:1875-8.  Back to cited text no. 19
    
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21.
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