Reviews of "Emergence of Transmissible SARS-CoV-2 Variants with Decreased Sensitivity to Antivirals in Immunocompromised Patients with Persistent Infections"

David Ussery; Jishnu Das

doi:doi:10.1162/2e3983f5.ed69afe3

Reviews of "Emergence of Transmissible SARS-CoV-2 Variants with Decreased Sensitivity to Antivirals in Immunocompromised Patients with Persistent Infections"

Reviewers: D Ussery (University of Arkansas) | 📘📘📘📘📘 • J Das (University of Pittsburgh) | 📗📗📗📗◻️

by David Ussery and Jishnu Das

Published onAug 04, 2024

This Pub is a Review of

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

by Mohammed Nooruzzaman, Katherine E.E. Johnson, Ruchi Rani, Eli J. Finkelsztein, Leonardo C. Caserta, Rosy P. Kodiyanplakkal, Wei Wang, Jingmei Hsu, Maria T. Salpietro, Stephanie Banakis, Joshua Albert, Lars Westblade, Claudio Zanettini, Luigi Marchionni, Rosemary Soave, Elodie Ghedin, Diego G. Diel, and Mirella Salvatore

Show Description
Published on Jun 18, 2024
www.medrxiv.org

Description

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.

To read the original manuscript, click the link above.

Summary of Reviews: This study evaluated the emergence of SARS-CoV-2 resistance during persistent infections in immunocompromised patients that received antiviral treatment. The authors found mutations conferring decreased sensibility to remdesivir and nirmatrelvir, which was overcome with combined therapy. Also, transmissibility of the mutated variant was shown in vitro. 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. Furthermore, they state that these results show immunocompromised people who repeatedly receive antiviral treatment can be the source of treatment-resistant variants.

Reviewer 1 (David U…) | 📘📘📘📘📘

Reviewer 2 (Jishnu D…) | 📗📗📗📗◻️

RR:C19 Strength of Evidence Scale Key

📕 ◻️◻️◻️◻️ = Misleading

📙📙 ◻️◻️◻️ = Not Informative

📒📒📒 ◻️◻️ = Potentially Informative

📗📗📗📗◻️ = Reliable

📘📘📘📘📘 = Strong

To read the reviews, click the links below.

Connections

1 of 2

A Supplement to this Pub

Review 1: "Emergence of Transmissible SARS-CoV-2 Variants with Decreased Sensitivity to Antivirals in Immunocompromised Patients with Persistent Infections"

by David Ussery

Show Description
Published on Aug 04, 2024
rrid.mitpress.mit.edu

Description

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.

A Supplement to this Pub

Review 2: "Emergence of Transmissible SARS-CoV-2 Variants with Decreased Sensitivity to Antivirals in Immunocompromised Patients with Persistent Infections"

by Jishnu Das

Show Description
Published on Aug 04, 2024
rrid.mitpress.mit.edu

Description

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.

License

Creative Commons Attribution 4.0 International License (CC-BY 4.0)

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Also, transmissibility of the mutated variant was shown in geometry dash lite

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