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

Autor:	Boshier FAT; Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, University College London, London, UK., Pang J; Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.; Division of Infection and Immunity, University College London, London, UK., Penner J; Department of Infectious Disease, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK., Parker M; Department of Infection, Immunity and Cardiovascular Diseases, The Florey Institute, University of Sheffield, Sheffield, UK., Alders N; Department of Infectious Disease, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK., Bamford A; Department of Infectious Disease, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK., Grandjean L; Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, University College London, London, UK., Grunewald S; Department of Metabolic Medicine, UCL Great Ormond Street Institute of Child Health, London, UK., Hatcher J; Department of Microbiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK., Best T; Department of Microbiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK., Dalton C; Department of Pharmacy, Great Ormond Street Hospital for Children NHS Trust, London, UK., Bynoe PD; Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, University College London, London, UK., Frauenfelder C; Department of Ears, Nose and Throat, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.; Division of Surgery, University of Adelaide, Adelaide, South Australia, Australia., Köeglmeier J; Department of Gastroenterology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK., Myerson P; Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, University College London, London, UK., Roy S; Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, University College London, London, UK., Williams R; Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, University College London, London, UK., de Silva TI; Department of Infection, Immunity and Cardiovascular Diseases, The Florey Institute, University of Sheffield, Sheffield, UK., Goldstein RA; Division of Infection and Immunity, University College London, London, UK., Breuer J; Department of Infection, Immunity and Inflammation, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.; Department of Microbiology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
Jazyk:	angličtina
Zdroj:	Journal of medical virology [J Med Virol] 2022 Jan; Vol. 94 (1), pp. 161-172. Date of Electronic Publication: 2021 Sep 04.
DOI:	10.1002/jmv.27285
Abstrakt:	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. (© 2021 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)
Databáze:	MEDLINE
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