Use of whole genome sequencing to identify low-frequency mutations in SARS-CoV-2 patients treated with remdesivir.

Autor: Nirmalarajah K; Sunnybrook Research Institute, Toronto, Ontario, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada., Yim W; Sunnybrook Research Institute, Toronto, Ontario, Canada., Aftanas P; Shared Hospital Laboratory, Toronto, Ontario, Canada., Li AX; Sinai Health System, Toronto, Ontario, Canada., Shigayeva A; Sinai Health System, Toronto, Ontario, Canada., Yip L; Sunnybrook Research Institute, Toronto, Ontario, Canada., Zhong Z; Sinai Health System, Toronto, Ontario, Canada., McGeer AJ; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.; Sinai Health System, Toronto, Ontario, Canada., Maguire F; Faculty of Computer Science, Dalhousie University, Halifax, Nova Scotia, Canada.; Department of Community Health & Epidemiology, Dalhousie University, Halifax, Nova Scotia, Canada., Mubareka S; Sunnybrook Research Institute, Toronto, Ontario, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada., Kozak R; Sunnybrook Research Institute, Toronto, Ontario, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
Jazyk: angličtina
Zdroj: Influenza and other respiratory viruses [Influenza Other Respir Viruses] 2023 Sep; Vol. 17 (9), pp. e13179.
DOI: 10.1111/irv.13179
Abstrakt: Background: Remdesivir (RDV) has been shown to reduce hospitalization and mortality in COVID-19 patients. Resistance mutations caused by RDV are rare and have been predominantly reported in patients who are on prolonged therapy and immunocompromised. We investigate the effects of RDV treatment on intra-host SARS-CoV-2 diversity and low-frequency mutations in moderately ill hospitalized COVID-19 patients and compare them to patients without RDV treatment.
Methods: From March 2020 to April 2022, sequential collections of nasopharyngeal and mid-turbinate swabs were obtained from 14 patients with and 30 patients without RDV treatment. Demographic and clinical data on all patients were reviewed. A total of 109 samples were sequenced and mutation analyses were performed.
Results: Previously reported drug resistant mutations in nsp12 were not identified during short courses of RDV therapy. In genes encoding and surrounding the replication complex (nsp6-nsp14), low-frequency minority variants were detected in 7/14 (50%) and 18/30 (60%) patients with and without RDV treatment, respectively. We did not detect significant differences in within-host diversity and positive selection between the RDV-treated and untreated groups.
Conclusions: Minimal intra-host variability and stochastic low-frequency variants detected in moderately ill patients suggests little selective pressure in patients receiving short courses of RDV. The barrier to RDV resistance is high in patients with moderate disease. Patients undergoing short regimens of RDV therapy should continue to be monitored.
(© 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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