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


Boshier, Florencia AT, Pang, Juanita, Penner, Justin, Parker, Matthew, Alders, Nele, Bamford, Alasdair, Grandjean, Louis, Grunewald, Stephanie, Hatcher, James, Best, Timothy et al (show 10 more authors) (2022) Evolution of viral variants in remdesivir‐treated and untreated SARS‐CoV‐2‐infected pediatrics patients. Journal of Medical Virology, 94 (1). pp. 161-172.

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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.

Item Type: Article
Uncontrolled Keywords: COVID-19 Genomics UK (COG-UK) consortium, Lung, Humans, Alanine, RNA, Viral, Adenosine Monophosphate, Antiviral Agents, Viral Load, Evolution, Molecular, Phylogeny, Drug Resistance, Viral, Virus Replication, Haplotypes, Adolescent, Child, Child, Preschool, Infant, Female, Male, COVID-19, SARS-CoV-2, COVID-19 Drug Treatment
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User: Symplectic Admin
Date Deposited: 09 May 2022 08:45
Last Modified: 16 Dec 2023 03:36
DOI: 10.1002/jmv.27285
Open Access URL: https://doi.org/10.1002/jmv.27285
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3154482
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