PMID- 36505092 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221221 IS - 2057-1577 (Print) IS - 2057-1577 (Electronic) IS - 2057-1577 (Linking) VI - 8 IP - 2 DP - 2022 TI - SARS-CoV-2 intra-host single-nucleotide variants associated with disease severity. PG - veac106 LID - 10.1093/ve/veac106 [doi] LID - veac106 AB - Variants of severe acute respiratory syndrome coronavirus 2 frequently arise within infected individuals. Here, we explored the level and pattern of intra-host viral diversity in association with disease severity. Then, we analyzed information underlying these nucleotide changes to infer the impetus including mutational signatures and immune selection from neutralizing antibody or T-cell recognition. From 23 January to 31 March 2020, a set of cross-sectional samples were collected from individuals with homogeneous founder virus regardless of disease severity. Intra-host single-nucleotide variants (iSNVs) were enumerated using deep sequencing. Human leukocyte antigen (HLA) alleles were genotyped by Sanger sequencing. Medical records were collected and reviewed by attending physicians. A total of 836 iSNVs (3-106 per sample) were identified and distributed in a highly individualized pattern. The number of iSNVs paced with infection duration peaked within days and declined thereafter. These iSNVs did not stochastically arise due to a strong bias toward C > U/G > A and U > C/A > G substitutions in reciprocal proportion with escalating disease severity. Eight nonsynonymous iSNVs in the receptor-binding domain could escape from neutralization, and eighteen iSNVs were significantly associated with specific HLA alleles. The level and pattern of iSNVs reflect the in vivo viral-host interaction and the disease pathogenesis. CI - (c) The Author(s) 2022. Published by Oxford University Press. FAU - Zhang, Yi AU - Zhang Y AD - Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China. FAU - Jiang, Ning AU - Jiang N AD - Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China. AD - State Key Laboratory of Genetic Engineering and Institute of Biostatistics, School of Life Sciences, Fudan University, Shanghai, China. FAU - Qi, Weiqiang AU - Qi W AD - Shanghai Public Health Clinical Center, Shanghai 200051, China. FAU - Li, Tao AU - Li T AD - Shanghai Public Health Clinical Center, Shanghai 200051, China. FAU - Zhang, Yumeng AU - Zhang Y AD - Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China. FAU - Wu, Jing AU - Wu J AD - Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China. FAU - Zhang, Haocheng AU - Zhang H AD - Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China. FAU - Zhou, Mingzhe AU - Zhou M AD - Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China. FAU - Cui, Peng AU - Cui P AD - Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China. FAU - Yu, Tong AU - Yu T AD - Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China. FAU - Fu, Zhangfan AU - Fu Z AD - Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China. FAU - Zhou, Yang AU - Zhou Y AD - Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China. FAU - Lin, Ke AU - Lin K AD - Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China. FAU - Wang, Hongyu AU - Wang H AD - Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China. FAU - Wei, Tongqing AU - Wei T AD - State Key Laboratory of Genetic Engineering and Institute of Biostatistics, School of Life Sciences, Fudan University, Shanghai, China. FAU - Zhu, Zhaoqin AU - Zhu Z AD - Shanghai Public Health Clinical Center, Shanghai 200051, China. AD - Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China. FAU - Ai, Jingwen AU - Ai J AUID- ORCID: 0000-0002-5152-1557 AD - Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China. FAU - Qiu, Chao AU - Qiu C AD - Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China. FAU - Zhang, Wenhong AU - Zhang W AUID- ORCID: 0000-0002-9165-3212 AD - Department of Infectious Diseases, National Clinical Research Center for Aging and Medicine, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai 200040, China. AD - State Key Laboratory of Genetic Engineering and Institute of Biostatistics, School of Life Sciences, Fudan University, Shanghai, China. LA - eng PT - Journal Article DEP - 20221129 PL - England TA - Virus Evol JT - Virus evolution JID - 101664675 PMC - PMC9728387 OTO - NOTNLM OT - COVID-19 OT - HLA OT - SARS-CoV-2 variants OT - immune response OT - intra-host OT - neutralization antibody EDAT- 2022/12/13 06:00 MHDA- 2022/12/13 06:01 PMCR- 2022/11/29 CRDT- 2022/12/12 10:54 PHST- 2022/04/19 00:00 [received] PHST- 2022/10/24 00:00 [revised] PHST- 2022/11/26 00:00 [accepted] PHST- 2022/12/12 10:54 [entrez] PHST- 2022/12/13 06:00 [pubmed] PHST- 2022/12/13 06:01 [medline] PHST- 2022/11/29 00:00 [pmc-release] AID - veac106 [pii] AID - 10.1093/ve/veac106 [doi] PST - epublish SO - Virus Evol. 2022 Nov 29;8(2):veac106. doi: 10.1093/ve/veac106. eCollection 2022.