Preliminary Clinical Experience of Molnupiravir to Prevent Progression of COVID-19 in Kidney Transplant Recipients.


Journal

Transplantation
ISSN: 1534-6080
Titre abrégé: Transplantation
Pays: United States
ID NLM: 0132144

Informations de publication

Date de publication:
01 11 2022
Historique:
pubmed: 3 8 2022
medline: 27 10 2022
entrez: 2 8 2022
Statut: ppublish

Résumé

Recently, different therapeutic lines have been tried in the initial stage of the disease of COVID-19, including remdesivir and molnupiravir. There is scarce evidence on the efficacy and safety of molnupiravir in kidney transplant recipients (KTRs). ingle-center prospective cohort study' all adult KTRs diagnosed with COVID-19 and treated with molnupiravir or remdesivir from January to April 2022 were included. Nine KTRs with SARS-CoV-2 (Omicron variant) infection and mild symptoms received molnupiravir in an outpatient basis and were compared with a cohort of similar patients treated with remdesivir (n = 7). Three patients in the molnupiravir cohort were in the early posttransplant period and received a basiliximab (n = 2) or antithymocite globulin-based induction (n = 1). One of the patients had been treated with methylprednisolone bolus and antithymocite globulin for an episode of acute rejection in the previous months. They were all vaccinated with mRNA vaccines' and all but 1 had serological response. Only one of the patients experienced clinical worsening despite molnupiravir treatment and developed pneumonia requiring hospital admission. None of the patients suffered adverse effects attributed to molnupiravir' and no adjustment of tacrolimus dose was needed. None of the patients treated with remdesivir progressed in COVID-19 severity. Our study suggests that KTRs with SARS-CoV-2 infection under treatment with molnupiravir have a good clinical evolution with a probable lower risk for hospitalization and no adverse effects. At the renal level, molnupiravir was well tolerated, with no evidence of nephrotoxicity secondary to the drug nor interactions with the immunosuppressive therapy.

Sections du résumé

BACKGROUND
Recently, different therapeutic lines have been tried in the initial stage of the disease of COVID-19, including remdesivir and molnupiravir. There is scarce evidence on the efficacy and safety of molnupiravir in kidney transplant recipients (KTRs).
METHODS
ingle-center prospective cohort study' all adult KTRs diagnosed with COVID-19 and treated with molnupiravir or remdesivir from January to April 2022 were included.
RESULTS
Nine KTRs with SARS-CoV-2 (Omicron variant) infection and mild symptoms received molnupiravir in an outpatient basis and were compared with a cohort of similar patients treated with remdesivir (n = 7). Three patients in the molnupiravir cohort were in the early posttransplant period and received a basiliximab (n = 2) or antithymocite globulin-based induction (n = 1). One of the patients had been treated with methylprednisolone bolus and antithymocite globulin for an episode of acute rejection in the previous months. They were all vaccinated with mRNA vaccines' and all but 1 had serological response. Only one of the patients experienced clinical worsening despite molnupiravir treatment and developed pneumonia requiring hospital admission. None of the patients suffered adverse effects attributed to molnupiravir' and no adjustment of tacrolimus dose was needed. None of the patients treated with remdesivir progressed in COVID-19 severity.
CONCLUSIONS
Our study suggests that KTRs with SARS-CoV-2 infection under treatment with molnupiravir have a good clinical evolution with a probable lower risk for hospitalization and no adverse effects. At the renal level, molnupiravir was well tolerated, with no evidence of nephrotoxicity secondary to the drug nor interactions with the immunosuppressive therapy.

Identifiants

pubmed: 35915545
doi: 10.1097/TP.0000000000004306
pii: 00007890-202211000-00021
doi:

Substances chimiques

Basiliximab 9927MT646M
molnupiravir YA84KI1VEW
Tacrolimus WM0HAQ4WNM
Immunosuppressive Agents 0
Methylprednisolone X4W7ZR7023

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

2200-2204

Informations de copyright

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.

Déclaration de conflit d'intérêts

I.L.A. has been a speaker for Merck and Pfizer and has received travel support from Gilead, Merck‚ and Novartis. O.L. has received a research grant from Pfizer and has been a speaker for Pfizer, Astellas, Novartis‚ and Merck. The authors declare no conflicts of interest.

Références

Medina-Pestana J, Cristelli MP, Foresto RD, et al. The higher COVID-19 fatality rate among kidney transplant recipients calls for further action. Transplantation. 2022;106:908–910.
Gentile I, Maraolo AE, Buonomo AR, et al. Monoclonal antibodies against SARS-CoV-2: potential game-changer still underused. Int J Environ Res Public Health. 2021;18:11159.
Liu L, Iketani S, Guo Y, et al. Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2. Nature. 2022;602:676–681.
Gottlieb RL, Vaca CE, Paredes R, et al. Early remdesivir to prevent progression to severe Covid-19 in outpatients. N Engl J Med. 2022;386:305–315.
Colaneri M, Amarasinghe N, Rezzonico L, et al. Early remdesivir to prevent severe COVID-19 in recipients of solid organ transplant: a real-life study from Northern Italy. Int J Infect Dis. 2022;121:157–160.
Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al.; MOVe-OUT Study Group. Molnupiravir for oral treatment of Covid-19 in nonhospitalized patients. N Engl J Med. 2022;386:509–520.
Vangeel L, Chiu W, De Jonghe S, et al. Remdesivir, molnupiravir and nirmatrelvir remain active against SARS-CoV-2 Omicron and other variants of concern. Antiviral Res. 2022;198:105252.
The Spanish Agency for Medicines and Health Products (Agencia Española de Medicamentos y Productos Sanitarios [AEMPS]), The Spanish Agency for Medicines and Health Products (Agencia Española de Medicamentos y Productos Sanitarios [AEMPS]), Criteria to assess the administration of new antiviral therapeutic alternatives against SARS-CoV-2 infection (in order of prioritization). 2022. Available at https://www.aemps.gob.es/medicamentos-de-uso-humano/acceso-a-medicamentos-en-situaciones-especiales/criterios-para-valorar-la-administracion-de-las-nuevas-alternativas-terapeuticas-antivirales-frente-a-la-infeccion-por-sars-cov-2/ . Accessed June 5,2022.
Radcliffe C, Palacios CF, Azar MM, et al. Real-world experience with available, outpatient COVID-19 therapies in solid organ transplant recipients during the omicron surge [published online ahead of print, 2022 May 18]. Am J Transplant. 2022;xx:1–6.
Cox RM, Wolf JD, Plemper RK. Therapeutically administered ribonucleoside analogue MK-4482/EIDD-2801 blocks SARS-CoV-2 transmission in ferrets. Nat Microbiol. 2021;6:11–18.
Accorsi EK, Britton A, Fleming-Dutra KE, et al. Association between 3 doses of mRNA COVID-19 vaccine and symptomatic infection caused by the SARS-CoV-2 Omicron and Delta variants. JAMA. 2022;327:639–651.
Jasuja S, Sagar G, Bahl A, et al. COVID-19 infection clinical profile, management, outcome, and antibody response in kidney transplant recipients: a single centre experience. Int J Nephrol. 2021;2021:3129411.

Auteurs

Miguel Villamarín (M)

Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

Ester Márquez-Algaba (E)

Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

Juliana Esperalba (J)

Microbiology Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

Manuel Perelló (M)

Nephrology Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

Ibai Los Arcos (I)

Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

David Campany (D)

Pharmacy Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

Francisco Moreso (F)

Nephrology Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.

Oscar Len (O)

Infectious Diseases Department, Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Barcelona, Spain.
CIBERINFEC, ISCIII-CIBER de Enfermedades Infecciosas, Subdirección General de Redes y Centros de Investigación Cooperativa, Instituto de Salud Carlos III, Madrid, Spain.

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