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Emerging Severe Acute Respiratory Syndrome Coronavirus 2 Mutation Hotspots Associated With Clinical Outcomes and Transmission

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes is critical for treatment and prevention. Here, we analyzed all high-coverage co...

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Autores principales: Pang, Xianwu, Li, Pu, Zhang, Lifeng, Que, Lusheng, Dong, Min, Xie, Bo, Wang, Qihui, Wei, Yinfeng, Xie, Xing, Li, Lanxiang, Yin, Chunyue, Wei, Liuchun, Huang, Kexin, Hua, Yiming, Zhou, Qingniao, Li, Yingfang, Yu, Lei, Li, Weidong, Mo, Zengnan, Zhang, Maosheng, Leng, Jing, Hu, Yanling
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558435/
https://www.ncbi.nlm.nih.gov/pubmed/34733263
http://dx.doi.org/10.3389/fmicb.2021.753823
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author Pang, Xianwu
Li, Pu
Zhang, Lifeng
Que, Lusheng
Dong, Min
Xie, Bo
Wang, Qihui
Wei, Yinfeng
Xie, Xing
Li, Lanxiang
Yin, Chunyue
Wei, Liuchun
Huang, Kexin
Hua, Yiming
Zhou, Qingniao
Li, Yingfang
Yu, Lei
Li, Weidong
Mo, Zengnan
Zhang, Maosheng
Leng, Jing
Hu, Yanling
author_facet Pang, Xianwu
Li, Pu
Zhang, Lifeng
Que, Lusheng
Dong, Min
Xie, Bo
Wang, Qihui
Wei, Yinfeng
Xie, Xing
Li, Lanxiang
Yin, Chunyue
Wei, Liuchun
Huang, Kexin
Hua, Yiming
Zhou, Qingniao
Li, Yingfang
Yu, Lei
Li, Weidong
Mo, Zengnan
Zhang, Maosheng
Leng, Jing
Hu, Yanling
author_sort Pang, Xianwu
collection PubMed
description Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes is critical for treatment and prevention. Here, we analyzed all high-coverage complete SARS-CoV-2 sequences from GISAID database from January 1, 2020, to January 1, 2021, to mine the mutation hotspots associated with clinical outcome and developed a model to predict the clinical outcome in different epidemic strains. Exploring the cause of mutation based on RNA-dependent RNA polymerase (RdRp) and RNA-editing enzyme, mutation was more likely to occur in severe and mild cases than in asymptomatic cases, especially A > G, C > T, and G > A mutations. The mutations associated with asymptomatic outcome were mainly in open reading frame 1ab (ORF1ab) and N genes; especially R6997P and V30L mutations occurred together and were correlated with asymptomatic outcome with high prevalence. D614G, Q57H, and S194L mutations were correlated with mild and severe outcome with high prevalence. Interestingly, the single-nucleotide variant (SNV) frequency was higher with high percentage of nt14408 mutation in RdRp in severe cases. The expression of ADAR and APOBEC was associated with clinical outcome. The model has shown that the asymptomatic percentage has increased over time, while there is high symptomatic percentage in Alpha, Beta, and Gamma. These findings suggest that mutation in the SARS-CoV-2 genome may have a direct association with clinical outcomes and pandemic. Our result and model are helpful to predict the prevalence of epidemic strains and to further study the mechanism of mutation causing severe disease.
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spelling pubmed-85584352021-11-02 Emerging Severe Acute Respiratory Syndrome Coronavirus 2 Mutation Hotspots Associated With Clinical Outcomes and Transmission Pang, Xianwu Li, Pu Zhang, Lifeng Que, Lusheng Dong, Min Xie, Bo Wang, Qihui Wei, Yinfeng Xie, Xing Li, Lanxiang Yin, Chunyue Wei, Liuchun Huang, Kexin Hua, Yiming Zhou, Qingniao Li, Yingfang Yu, Lei Li, Weidong Mo, Zengnan Zhang, Maosheng Leng, Jing Hu, Yanling Front Microbiol Microbiology Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Understanding the influence of mutations in the SARS-CoV-2 gene on clinical outcomes is critical for treatment and prevention. Here, we analyzed all high-coverage complete SARS-CoV-2 sequences from GISAID database from January 1, 2020, to January 1, 2021, to mine the mutation hotspots associated with clinical outcome and developed a model to predict the clinical outcome in different epidemic strains. Exploring the cause of mutation based on RNA-dependent RNA polymerase (RdRp) and RNA-editing enzyme, mutation was more likely to occur in severe and mild cases than in asymptomatic cases, especially A > G, C > T, and G > A mutations. The mutations associated with asymptomatic outcome were mainly in open reading frame 1ab (ORF1ab) and N genes; especially R6997P and V30L mutations occurred together and were correlated with asymptomatic outcome with high prevalence. D614G, Q57H, and S194L mutations were correlated with mild and severe outcome with high prevalence. Interestingly, the single-nucleotide variant (SNV) frequency was higher with high percentage of nt14408 mutation in RdRp in severe cases. The expression of ADAR and APOBEC was associated with clinical outcome. The model has shown that the asymptomatic percentage has increased over time, while there is high symptomatic percentage in Alpha, Beta, and Gamma. These findings suggest that mutation in the SARS-CoV-2 genome may have a direct association with clinical outcomes and pandemic. Our result and model are helpful to predict the prevalence of epidemic strains and to further study the mechanism of mutation causing severe disease. Frontiers Media S.A. 2021-10-18 /pmc/articles/PMC8558435/ /pubmed/34733263 http://dx.doi.org/10.3389/fmicb.2021.753823 Text en Copyright © 2021 Pang, Li, Zhang, Que, Dong, Xie, Wang, Wei, Xie, Li, Yin, Wei, Huang, Hua, Zhou, Li, Yu, Li, Mo, Zhang, Leng and Hu. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Pang, Xianwu
Li, Pu
Zhang, Lifeng
Que, Lusheng
Dong, Min
Xie, Bo
Wang, Qihui
Wei, Yinfeng
Xie, Xing
Li, Lanxiang
Yin, Chunyue
Wei, Liuchun
Huang, Kexin
Hua, Yiming
Zhou, Qingniao
Li, Yingfang
Yu, Lei
Li, Weidong
Mo, Zengnan
Zhang, Maosheng
Leng, Jing
Hu, Yanling
Emerging Severe Acute Respiratory Syndrome Coronavirus 2 Mutation Hotspots Associated With Clinical Outcomes and Transmission
title Emerging Severe Acute Respiratory Syndrome Coronavirus 2 Mutation Hotspots Associated With Clinical Outcomes and Transmission
title_full Emerging Severe Acute Respiratory Syndrome Coronavirus 2 Mutation Hotspots Associated With Clinical Outcomes and Transmission
title_fullStr Emerging Severe Acute Respiratory Syndrome Coronavirus 2 Mutation Hotspots Associated With Clinical Outcomes and Transmission
title_full_unstemmed Emerging Severe Acute Respiratory Syndrome Coronavirus 2 Mutation Hotspots Associated With Clinical Outcomes and Transmission
title_short Emerging Severe Acute Respiratory Syndrome Coronavirus 2 Mutation Hotspots Associated With Clinical Outcomes and Transmission
title_sort emerging severe acute respiratory syndrome coronavirus 2 mutation hotspots associated with clinical outcomes and transmission
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558435/
https://www.ncbi.nlm.nih.gov/pubmed/34733263
http://dx.doi.org/10.3389/fmicb.2021.753823
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