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Evolution of viral variants in remdesivir-treated and untreated SARS-CoV-2-infected pediatrics patients

Boshier, FAT; Pang, J; Penner, J; Parker, M; Alders, N; Bamford, A; Grandjean, L; ... Breuer, J; + view all (2021) Evolution of viral variants in remdesivir-treated and untreated SARS-CoV-2-infected pediatrics patients. Journal of Medical Virology 10.1002/jmv.27285. (In press). Green open access

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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.

Type: Article
Title: Evolution of viral variants in remdesivir-treated and untreated SARS-CoV-2-infected pediatrics patients
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/jmv.27285
Publisher version: https://doi.org/10.1002/jmv.27285
Language: English
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, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Intrahost, remdesivir, SARS‐CoV‐2, viral‐variants
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10134551
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