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Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections.
- Source :
-
Nature communications [Nat Commun] 2024 Sep 18; Vol. 15 (1), pp. 7999. Date of Electronic Publication: 2024 Sep 18. - Publication Year :
- 2024
-
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 (n = 3) or therapeutic monoclonal antibodies (n = 4). 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 sequentially treated with nirmatrelvir-ritonavir and remdesivir. 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.<br /> (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
- Subjects :
- Animals
Humans
Female
Male
Middle Aged
Aged
Mesocricetus
Adult
Cricetinae
Leucine
Lactams
Proline
Nitriles
Coronavirus RNA-Dependent RNA Polymerase
SARS-CoV-2 genetics
SARS-CoV-2 drug effects
Alanine analogs & derivatives
Alanine therapeutic use
Alanine pharmacology
Adenosine Monophosphate analogs & derivatives
Adenosine Monophosphate therapeutic use
Adenosine Monophosphate pharmacology
Antiviral Agents therapeutic use
Antiviral Agents pharmacology
COVID-19 virology
Immunocompromised Host
Drug Resistance, Viral genetics
COVID-19 Drug Treatment
Ritonavir therapeutic use
Ritonavir pharmacology
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 15
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 39294134
- Full Text :
- https://doi.org/10.1038/s41467-024-51924-3