Emergence of transmissible SARS-CoV-2 variants with decreased sensitivity to antivirals in immunocompromised patients with persistent infections
This article has been Reviewed by the following groups
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- Evaluated articles (Rapid Reviews Infectious Diseases)
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 .
Article activity feed
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Jishnu Das
Review 2: "Emergence of Transmissible SARS-CoV-2 Variants with Decreased Sensitivity to Antivirals in Immunocompromised Patients with Persistent Infections"
The reviewers agree that the study is well designed and provides reliable evidence. They make very minor comments regarding potential questions to pursue in order to better characterize the results.
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David Ussery
Review 1: "Emergence of Transmissible SARS-CoV-2 Variants with Decreased Sensitivity to Antivirals in Immunocompromised Patients with Persistent Infections"
The reviewers agree that the study is well designed and provides reliable evidence. They make very minor comments regarding potential questions to pursue in order to better characterize the results.
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Strength of evidence
Reviewers: D Ussery (University of Arkansas) | πππππ
J Das (University of Pittsburgh) | ππππβ»οΈ -