Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections.

TitleEmergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections.
Publication TypeJournal Article
Year of Publication2024
AuthorsNooruzzaman M, Johnson KEE, Rani R, Finkelsztein EJ, Caserta LC, Kodiyanplakkal RP, Wang W, Hsu JM, Salpietro MT, Banakis S, Albert J, Westblade L, Zanettini C, Marchionni L, Soave R, Ghedin E, Diel DG, Salvatore M
JournalmedRxiv
Date Published2024 Jun 18
Abstract

We investigated the impact of antiviral treatment on the emergence of SARS-CoV-2 resistance during persistent infections in immunocompromised patients (n=15). All patients received remdesivir and some also received nirmatrelvir-ritonavir or monoclonal antibodies. Sequence analysis showed that nine patients carried viruses with mutations in the nsp12 (RNA dependent RNA polymerase), while four had viruses with nsp5 (3C protease) mutations. Infectious SARS-CoV-2 with a double mutation in nsp5 (T169I) and nsp12 (V792I) was recovered from respiratory secretions 77 days after initial COVID-19 diagnosis from a patient treated with remdesivir and nirmatrelvir-ritonavir. In vitro characterization confirmed its decreased sensitivity to remdesivir and nirmatrelvir, which was overcome by combined antiviral treatment. Studies in golden Syrian hamsters demonstrated efficient transmission to contact animals. This study documents the isolation of SARS-CoV-2 carrying resistance mutations to both nirmatrelvir and remdesivir from a patient and demonstrates its transmissibility in vivo.

DOI10.1101/2024.06.14.24308523
Alternate JournalmedRxiv
PubMed ID38946967
PubMed Central IDPMC11213110
Grant ListR01 AI166791 / AI / NIAID NIH HHS / United States
UL1 TR002384 / TR / NCATS NIH HHS / United States
Related Faculty: 
Luigi Marchionni, M.D., Ph.D. Lars Westblade, Ph.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700