Remdesivir and molnupiravir had comparable efficacy in lung transplant recipients with mild-to-moderate COVID-19: a single center experience

Razia et al., Frontiers in Transplantation, doi:10.3389/frtra.2024.1408289

Jul 2024

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Retrospective 113 lung transplant recipients with mild-to-moderate COVID-19 showing higher mortality with remdesivir and molnupiravir in unadjusted analysis, with statistical significance for remdesivir. mAb PrEP and treatment and the dominant variant favored molnupiravir compared with the control group, however they favored the control group compared with remdesivir.

Gérard, Zhou, Wu, Kamo, Choi, Kim show significantly increased risk of acute kidney injury with remdesivir.

This study is excluded in meta analysis: excessive unadjusted differences between groups.

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Study covers molnupiravir and remdesivir.

risk of death, 1520.0% higher, RR 16.20, p < 0.001, treatment 9 of 30 (30.0%), control 1 of 54 (1.9%).

risk of mechanical ventilation, 620.0% higher, RR 7.20, p = 0.05, treatment 4 of 30 (13.3%), control 1 of 54 (1.9%).

risk of ICU admission, 710.0% higher, RR 8.10, p = 0.001, treatment 9 of 30 (30.0%), control 2 of 54 (3.7%).

risk of hospitalization, 93.8% higher, RR 1.94, p = 0.05, treatment 14 of 30 (46.7%), control 13 of 54 (24.1%).

Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates

1. Gérard et al., Remdesivir and Acute Renal Failure: A Potential Safety Signal From Disproportionality Analysis of the WHO Safety Database, Clinical Pharmacology & Therapeutics, doi:10.1002/cpt.2145.wiley.com, doi.org.

2. Zhou et al., Acute Kidney Injury and Drugs Prescribed for COVID-19 in Diabetes Patients: A Real-World Disproportionality Analysis, Frontiers in Pharmacology, doi:10.3389/fphar.2022.833679.frontiersin.org, doi.org.

3. Wu et al., Acute Kidney Injury Associated With Remdesivir: A Comprehensive Pharmacovigilance Analysis of COVID-19 Reports in FAERS, Frontiers in Pharmacology, doi:10.3389/fphar.2022.692828.frontiersin.org, doi.org.

4. Kamo et al., Association of Antiviral Drugs for the Treatment of COVID-19 With Acute Renal Failure, In Vivo, doi:10.21873/invivo.13637.iiarjournals.org, doi.org.

5. Choi et al., Comparative effectiveness of combination therapy with nirmatrelvir–ritonavir and remdesivir versus monotherapy with remdesivir or nirmatrelvir–ritonavir in patients hospitalised with COVID-19: a target trial emulation study, The Lancet Infectious Diseases, doi:10.1016/S1473-3099(24)00353-0.sciencedirect.com, doi.org.

6. Kim et al., Investigating the Safety Profile of Fast‐Track COVID‐19 Drugs Using the FDA Adverse Event Reporting System Database: A Comparative Observational Study, Pharmacoepidemiology and Drug Safety, doi:10.1002/pds.70043.wiley.com, doi.org.

Razia et al., 4 Jul 2024, retrospective, Italy, peer-reviewed, 6 authors, study period March 2020 - August 2022. Contact: sofya.tokman@dignityhealth.org.

This Paper Remdesivir All

Remdesivir and molnupiravir had comparable efficacy in lung transplant recipients with mild-to-moderate COVID-19: a single center experience

Deepika Razia, Devika Sindu, Lauren Cherrier, Katherine Grief, Rajat Walia, Sofya Tokman

Frontiers in Transplantation, doi:10.3389/frtra.2024.1408289

Introduction: Remdesivir (REM) and molnupiravir (MOL) are commonly used to treat lung transplant recipients (LTRs) with COVID-19; however, the clinical efficacy of these medications is yet to be compared. In this retrospective cohort study, we compared the clinical outcomes between LTRs with mild-tomoderate COVID-19 treated with REM and those treated with MOL. Methods and Results: Between March 2020 and August 2022, 195 LTRs developed COVID-19 at our center. After excluding 82 who presented with severe disease requiring hospitalization, the remaining 113 were included in the analysis: 54 did not receive antiviral treatment, 30 were treated with REM, and 29 were treated with MOL. Adjusted multivariable logistic regression analysis showed similar rates of hospitalization (adjusted odds ratio (aOR) 1.169, [95% confidence interval (95% CI) 0.105-12.997, p = 0.899], ICU admission (aOR 0.822, 95% CI 0.042-16.220, p = 0.898), mechanical ventilation (aOR 0.903, 95% CI 0.015-55.124, p = 0.961), and COVID-19related mortality (aOR 0.822, 95% CI 0.042-16.220, p = 0.898) between LTRs treated with REM and those treated with MOL for mild-to-moderate COVID-19, irrespective of SARS-CoV-2 strain. Conclusion: MOL may be a suitable alternative to REM to treat LTRs with mildto-moderate COVID-19, and the choice of antiviral therapy can be driven by practical considerations such as route of administration and drug availability.

Ethics statement The studies involving humans were approved by The Institutional Review Board of St. Joseph's Hospital and Medical Center. The studies were conducted in accordance with the local legislation and institutional requirements. The Ethics Committee/institutional review board waived the requirement of written informed consent for participation from the participants or the participants' legal guardians/next of kin because the study was a retrospective data analysis study with no identifiable patient information. Author contributions Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

Bhimraj, Morgan, Shumaker, Baden, Cheng et al., Infectious Diseases Society of America Guidelines on the treatment and management of patients with coronavirus disease 2019 (COVID-19), Clin Infect Dis, doi:10.1093/cid/ciac724

Dauriat, Beaumont, Nguyen, Picard, Penhouet et al., Efficacy of three COVID-19 vaccine doses in lung transplant recipients: a multicentre cohort study, Eur Respir J, doi:10.1183/13993003.00502-2022

Gottlieb, Vaca, Paredes, Mera, Webb et al., Early remdesivir to prevent progression to severe COVID-19 in outpatients, N Engl J Med, doi:10.1056/NEJMoa2116846

Hallett, Greenberg, Boyarsky, Shah, Ou et al., SARS-CoV-2 messenger RNA vaccine antibody response and reactogenicity in heart and lung transplant recipients, J Heart Lung Transplant, doi:10.1016/j.healun.2021.07.026

Havlin, Svorcova, Dvorackova, Lastovicka, Lischke et al., Immunogenicity of BNT162b2 mRNA COVID-19 vaccine and SARS-CoV-2 infection in lung transplant recipients, J Heart Lung Transplant, doi:10.1016/j.healun.2021.05.004

Lo, Jordan, Arvey, Sudhamsu, Shrivastava-Ranjan et al., GS-5734 and its parent nucleoside analog inhibit filo-, pneumo-, and paramyxoviruses, Sci Rep, doi:10.1038/srep43395

Narasimhan, Mahimainathan, Clark, Usmani, Cao et al., Serological response in lung transplant recipients after two doses of SARS-CoV-2 mRNA vaccines, Vaccines, doi:10.3390/vaccines9070708

Peled, Lavee, Sternik, Segev, Wieder-Finesod, BNT162b2 vaccination in heart transplant recipients: clinical experience and antibody response, J Heart Lung Transplant, doi:10.1016/j.healun.2021.04.003

Razia, None

Sheahan, Sims, Graham, Menachery, Gralinski et al., Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses, Sci Transl Med, doi:10.1126/scitranslmed.aal3653

Sindu, Razia, Bay, Padiyar, Grief et al., Evolving impact of the COVID-19 pandemic on lung transplant recipients: a single-center experience, J Heart Lung Transplant, doi:10.1016/j.healun.2023.10.010

Warren, Jordan, Lo, Ray, Mackman et al., Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys, Nature, doi:10.1038/nature17180

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