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Virological and genomic analysis of SARS-CoV-2 from a favipiravir clinical trial cohort

INTRODUCTION: Several clinical studies have reported the efficacy of favipiravir in reducing viral load and shortening the duration of symptoms. However, the viability of SARS-CoV-2 in the context of favipiravir therapy and the potential for resistance development is unclear. METHODS: We sequenced S...

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Autores principales: Suzuki, Masahiro, Imai, Takumi, Sakurai, Aki, Komoto, Satoshi, Ide, Tomihiko, Lim, Chang Kweng, Shintani, Ayumi, Doi, Yohei, Murata, Takayuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196299/
https://www.ncbi.nlm.nih.gov/pubmed/34176716
http://dx.doi.org/10.1016/j.jiac.2021.06.010
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author Suzuki, Masahiro
Imai, Takumi
Sakurai, Aki
Komoto, Satoshi
Ide, Tomihiko
Lim, Chang Kweng
Shintani, Ayumi
Doi, Yohei
Murata, Takayuki
author_facet Suzuki, Masahiro
Imai, Takumi
Sakurai, Aki
Komoto, Satoshi
Ide, Tomihiko
Lim, Chang Kweng
Shintani, Ayumi
Doi, Yohei
Murata, Takayuki
author_sort Suzuki, Masahiro
collection PubMed
description INTRODUCTION: Several clinical studies have reported the efficacy of favipiravir in reducing viral load and shortening the duration of symptoms. However, the viability of SARS-CoV-2 in the context of favipiravir therapy and the potential for resistance development is unclear. METHODS: We sequenced SARS-CoV-2 in nasopharyngeal specimens collected from patients who participated in a randomized clinical trial of favipiravir at hospitals across Japan between March and May 2020. Paired genomes were sequenced from those who remained RT-PCR-positive 5–8 days into favipiravir therapy. Daily nasopharyngeal specimens from 69 patients who were RT-PCR-positive at randomization were examined for a cytopathic effect (CPE). RESULTS: Some strains early in the trial belonged to clade 19 B, whereas the majority belonged to clade 20 B. The median time from the disease onset to negative CPE was 9 days. CPE was strongly correlated with the time from disease onset, viral load, age, and male sex. Among 23 patients for whom paired genomes were available, all except one had identical genomes. Two mutations were observed in one patient who received favipiravir, neither in the RdRp gene. CONCLUSIONS: The SARS-CoV-2 genome distribution in this clinical trial conducted in Japan reflected the early influx of strains from China followed by replacement by strains from Europe. CPE was significantly associated with age, male sex, and viral loads but not with favipiravir therapy. There was no evidence of resistance development during favipiravir therapy.
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spelling pubmed-81962992021-06-15 Virological and genomic analysis of SARS-CoV-2 from a favipiravir clinical trial cohort Suzuki, Masahiro Imai, Takumi Sakurai, Aki Komoto, Satoshi Ide, Tomihiko Lim, Chang Kweng Shintani, Ayumi Doi, Yohei Murata, Takayuki J Infect Chemother Original Article INTRODUCTION: Several clinical studies have reported the efficacy of favipiravir in reducing viral load and shortening the duration of symptoms. However, the viability of SARS-CoV-2 in the context of favipiravir therapy and the potential for resistance development is unclear. METHODS: We sequenced SARS-CoV-2 in nasopharyngeal specimens collected from patients who participated in a randomized clinical trial of favipiravir at hospitals across Japan between March and May 2020. Paired genomes were sequenced from those who remained RT-PCR-positive 5–8 days into favipiravir therapy. Daily nasopharyngeal specimens from 69 patients who were RT-PCR-positive at randomization were examined for a cytopathic effect (CPE). RESULTS: Some strains early in the trial belonged to clade 19 B, whereas the majority belonged to clade 20 B. The median time from the disease onset to negative CPE was 9 days. CPE was strongly correlated with the time from disease onset, viral load, age, and male sex. Among 23 patients for whom paired genomes were available, all except one had identical genomes. Two mutations were observed in one patient who received favipiravir, neither in the RdRp gene. CONCLUSIONS: The SARS-CoV-2 genome distribution in this clinical trial conducted in Japan reflected the early influx of strains from China followed by replacement by strains from Europe. CPE was significantly associated with age, male sex, and viral loads but not with favipiravir therapy. There was no evidence of resistance development during favipiravir therapy. Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. 2021-09 2021-06-12 /pmc/articles/PMC8196299/ /pubmed/34176716 http://dx.doi.org/10.1016/j.jiac.2021.06.010 Text en © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Original Article
Suzuki, Masahiro
Imai, Takumi
Sakurai, Aki
Komoto, Satoshi
Ide, Tomihiko
Lim, Chang Kweng
Shintani, Ayumi
Doi, Yohei
Murata, Takayuki
Virological and genomic analysis of SARS-CoV-2 from a favipiravir clinical trial cohort
title Virological and genomic analysis of SARS-CoV-2 from a favipiravir clinical trial cohort
title_full Virological and genomic analysis of SARS-CoV-2 from a favipiravir clinical trial cohort
title_fullStr Virological and genomic analysis of SARS-CoV-2 from a favipiravir clinical trial cohort
title_full_unstemmed Virological and genomic analysis of SARS-CoV-2 from a favipiravir clinical trial cohort
title_short Virological and genomic analysis of SARS-CoV-2 from a favipiravir clinical trial cohort
title_sort virological and genomic analysis of sars-cov-2 from a favipiravir clinical trial cohort
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196299/
https://www.ncbi.nlm.nih.gov/pubmed/34176716
http://dx.doi.org/10.1016/j.jiac.2021.06.010
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