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Intra-host Variation and Evolutionary Dynamics of SARS-CoV-2 Population in COVID-19 Patients

Yanqun Wang, Daxi Wang, Lu Zhang, Wanying Sun, Zhaoyong Zhang, Weijun Chen, Airu Zhu, Yongbo Huang, Fei Xiao, Jinxiu Yao, Mian Gan, Fang Li, Ling luo, Xiaofang Huang, Yanjun Zhang, Sook-san Wong, Xinyi Cheng, Jingkai Ji, Zhihua Ou, Minfeng Xiao, Min Li, Jiandong Li, Peidi Ren, Ziqing Deng, Huanzi Zhong, Huanming Yang, Jian Wang, Xun Xu, Tie Song, Chris Ka Pun Mok, Malik Peiris, Nanshan Zhong, Jingxian Zhao, Yimin Li, View ORCID ProfileJunhua Li, Jincun Zhao
doi: https://doi.org/10.1101/2020.05.20.103549
Yanqun Wang
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China
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Daxi Wang
2BGI-Shenzhen, Shenzhen, 518083, China
3Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, Shenzhen, 518083, China
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Lu Zhang
4Institute of Infectious disease, Guangzhou Eighth People’s Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510060, China
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Wanying Sun
2BGI-Shenzhen, Shenzhen, 518083, China
3Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, Shenzhen, 518083, China
5BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, 518083, China
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Zhaoyong Zhang
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China
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Weijun Chen
5BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, 518083, China
6BGI PathoGenesis Pharmaceutical Technology Co., Ltd, BGI-Shenzhen, Shenzhen, 518083, China
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Airu Zhu
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China
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Yongbo Huang
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China
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Fei Xiao
7Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Biomedical Imaging, Guangdong Provincial Engineering Research Center of Molecular Imaging. The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong, 519000, China
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Jinxiu Yao
8Yangjiang People’s Hospital, Yangjiang, Guangdong, China
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Mian Gan
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China
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Fang Li
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China
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Ling luo
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China
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Xiaofang Huang
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China
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Yanjun Zhang
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China
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Sook-san Wong
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China
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Xinyi Cheng
2BGI-Shenzhen, Shenzhen, 518083, China
9School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China
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Jingkai Ji
2BGI-Shenzhen, Shenzhen, 518083, China
3Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, Shenzhen, 518083, China
10School of Future Technology, University of Chinese Academy of Sciences, Beijing 101408, China
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Zhihua Ou
2BGI-Shenzhen, Shenzhen, 518083, China
3Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, Shenzhen, 518083, China
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Minfeng Xiao
2BGI-Shenzhen, Shenzhen, 518083, China
3Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, Shenzhen, 518083, China
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Min Li
2BGI-Shenzhen, Shenzhen, 518083, China
3Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, Shenzhen, 518083, China
5BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, 518083, China
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Jiandong Li
2BGI-Shenzhen, Shenzhen, 518083, China
3Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, Shenzhen, 518083, China
5BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, 518083, China
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Peidi Ren
2BGI-Shenzhen, Shenzhen, 518083, China
3Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, Shenzhen, 518083, China
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Ziqing Deng
2BGI-Shenzhen, Shenzhen, 518083, China
3Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, Shenzhen, 518083, China
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Huanzi Zhong
2BGI-Shenzhen, Shenzhen, 518083, China
3Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, Shenzhen, 518083, China
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Huanming Yang
2BGI-Shenzhen, Shenzhen, 518083, China
11James D. Watson Institute of Genome Science, Hangzhou, 310008, China
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Jian Wang
2BGI-Shenzhen, Shenzhen, 518083, China
11James D. Watson Institute of Genome Science, Hangzhou, 310008, China
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Xun Xu
2BGI-Shenzhen, Shenzhen, 518083, China
12Guangdong Provincial Key Laboratory of Genome Read and Write, BGI-Shenzhen, Shenzhen, 518120, China
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Tie Song
13Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, Guangdong, 511430, China
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Chris Ka Pun Mok
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China
14The HKU–Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, 19406, China
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Malik Peiris
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China
14The HKU–Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, 19406, China
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Nanshan Zhong
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China
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Jingxian Zhao
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China
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  • For correspondence: zhaojincun@gird.cn lijunhua@genomics.cn dryiminli@vip.163.com zhaojingxian@gird.cn
Yimin Li
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China
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  • For correspondence: zhaojincun@gird.cn lijunhua@genomics.cn dryiminli@vip.163.com zhaojingxian@gird.cn
Junhua Li
2BGI-Shenzhen, Shenzhen, 518083, China
3Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, Shenzhen, 518083, China
9School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China
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  • ORCID record for Junhua Li
  • For correspondence: zhaojincun@gird.cn lijunhua@genomics.cn dryiminli@vip.163.com zhaojingxian@gird.cn
Jincun Zhao
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, China
4Institute of Infectious disease, Guangzhou Eighth People’s Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510060, China
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  • For correspondence: zhaojincun@gird.cn lijunhua@genomics.cn dryiminli@vip.163.com zhaojingxian@gird.cn
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ABSTRACT

As of middle May 2020, the causative agent of COVID-19, SARS-CoV-2, has infected over 4 million people with more than 300 thousand death as official reports1,2. The key to understanding the biology and virus-host interactions of SARS-CoV-2 requires the knowledge of mutation and evolution of this virus at both inter- and intra-host levels. However, despite quite a few polymorphic sites identified among SARS-CoV-2 populations, intra-host variant spectra and their evolutionary dynamics remain mostly unknown. Here, using deep sequencing data, we achieved and characterized consensus genomes and intra-host genomic variants from 32 serial samples collected from eight patients with COVID-19. The 32 consensus genomes revealed the coexistence of different genotypes within the same patient. We further identified 40 intra-host single nucleotide variants (iSNVs). Most (30/40) iSNVs presented in single patient, while ten iSNVs were found in at least two patients or identical to consensus variants. Comparison of allele frequencies of the iSNVs revealed genetic divergence between intra-host populations of the respiratory tract (RT) and gastrointestinal tract (GIT), mostly driven by bottleneck events among intra-host transmissions. Nonetheless, we observed a maintained viral genetic diversity within GIT, showing an increased population with accumulated mutations developed in the tissue-specific environments. The iSNVs identified here not only show spatial divergence of intra-host viral populations, but also provide new insights into the complex virus-host interactions.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://db.cngb.org/

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Intra-host Variation and Evolutionary Dynamics of SARS-CoV-2 Population in COVID-19 Patients
Yanqun Wang, Daxi Wang, Lu Zhang, Wanying Sun, Zhaoyong Zhang, Weijun Chen, Airu Zhu, Yongbo Huang, Fei Xiao, Jinxiu Yao, Mian Gan, Fang Li, Ling luo, Xiaofang Huang, Yanjun Zhang, Sook-san Wong, Xinyi Cheng, Jingkai Ji, Zhihua Ou, Minfeng Xiao, Min Li, Jiandong Li, Peidi Ren, Ziqing Deng, Huanzi Zhong, Huanming Yang, Jian Wang, Xun Xu, Tie Song, Chris Ka Pun Mok, Malik Peiris, Nanshan Zhong, Jingxian Zhao, Yimin Li, Junhua Li, Jincun Zhao
bioRxiv 2020.05.20.103549; doi: https://doi.org/10.1101/2020.05.20.103549
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Intra-host Variation and Evolutionary Dynamics of SARS-CoV-2 Population in COVID-19 Patients
Yanqun Wang, Daxi Wang, Lu Zhang, Wanying Sun, Zhaoyong Zhang, Weijun Chen, Airu Zhu, Yongbo Huang, Fei Xiao, Jinxiu Yao, Mian Gan, Fang Li, Ling luo, Xiaofang Huang, Yanjun Zhang, Sook-san Wong, Xinyi Cheng, Jingkai Ji, Zhihua Ou, Minfeng Xiao, Min Li, Jiandong Li, Peidi Ren, Ziqing Deng, Huanzi Zhong, Huanming Yang, Jian Wang, Xun Xu, Tie Song, Chris Ka Pun Mok, Malik Peiris, Nanshan Zhong, Jingxian Zhao, Yimin Li, Junhua Li, Jincun Zhao
bioRxiv 2020.05.20.103549; doi: https://doi.org/10.1101/2020.05.20.103549

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