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Boshier, F.A.T., Pang, J., Penner, J. et al. (17 more authors) (2021) Evolution of viral variants in remdesivir-treated and untreated SARS-CoV-2-infected pediatrics patients. Journal of Medical Virology, 94 (1). pp. 161-172. ISSN 0146-6615
Abstract
Detailed information on intrahost viral evolution in SARS-CoV-2 with and without treatment is limited. Sequential viral loads and deep sequencing of SARS-CoV-2 from the upper respiratory tract of nine hospitalized children, three of whom were treated with remdesivir, revealed that remdesivir treatment suppressed viral load in one patient but not in a second infected with an identical strain without any evidence of drug resistance found. Reduced levels of subgenomic RNA during treatment of the second patient, suggest an additional effect of remdesivir on viral replication. Haplotype reconstruction uncovered persistent SARS-CoV-2 variant genotypes in four patients. These likely arose from within-host evolution, although superinfection cannot be excluded in one case. Although our dataset is small, observed sample-to-sample heterogeneity in variant frequencies across four of nine patients suggests the presence of discrete viral populations in the lung with incomplete population sampling in diagnostic swabs. Such compartmentalization could compromise the penetration of remdesivir into the lung, limiting the drugs in vivo efficacy, as has been observed in other lung infections.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2021 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, (http://creativecommons.org/licenses/by/4.0/) which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | intrahost; remdesivir; SARS-CoV-2; viral-variants |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Infection and Immunity (Sheffield) |
Funding Information: | Funder Grant number PUBLIC HEALTH ENGLAND UNSPECIFIED |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 05 Oct 2021 16:09 |
Last Modified: | 11 May 2023 14:48 |
Status: | Published |
Publisher: | Wiley |
Refereed: | Yes |
Identification Number: | 10.1002/jmv.27285 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:178788 |
Available Versions of this Item
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Remdesivir induced viral RNA and subgenomic RNA suppression, and evolution of viral variants in SARS-CoV-2 infected patients. (deposited 11 May 2023 14:47)
- Evolution of viral variants in remdesivir-treated and untreated SARS-CoV-2-infected pediatrics patients. (deposited 05 Oct 2021 16:09) [Currently Displayed]