Population Bottlenecks and Intra-host Evolution During Human-to-Human Transmission of SARS-CoV-2

Daxi Wang; Yanqun Wang; Wanying Sun; Lu Zhang; Jingkai Ji; Zhaoyong Zhang; Xinyi Cheng; Yimin Li; Fei Xiao; Airu Zhu; Bei Zhong; Shicong Ruan; Jiandong Li; Peidi Ren; Zhihua Ou; Minfeng Xiao; Min Li; Ziqing Deng; Huanzi Zhong; Fuqiang Li; Wen-Jing Wang; Yongwei Zhang; Weijun Chen; Shida Zhu; Xun Xu; Xin Jin; Jingxian Zhao; Nanshan Zhong; Wenwei Zhang; Jincun Zhao; Junhua Li; Yonghao Xu

doi:10.3389/fmed.2021.585358

Population Bottlenecks and Intra-host Evolution During Human-to-Human Transmission of SARS-CoV-2

Front Med (Lausanne). 2021 Feb 15:8:585358. doi: 10.3389/fmed.2021.585358. eCollection 2021.

Authors

Daxi Wang^{1

2}, Yanqun Wang³, Wanying Sun^{1

2

4}, Lu Zhang^{3

5}, Jingkai Ji^{1

2}, Zhaoyong Zhang³, Xinyi Cheng^{1

2

6}, Yimin Li³, Fei Xiao⁷, Airu Zhu³, Bei Zhong⁸, Shicong Ruan⁹, Jiandong Li^{1

2

4}, Peidi Ren^{1

2}, Zhihua Ou^{1

2}, Minfeng Xiao^{1

2}, Min Li^{1

2

4}, Ziqing Deng^{1

2}, Huanzi Zhong^{1

2

10}, Fuqiang Li^{1

2

11}, Wen-Jing Wang^{1

11}, Yongwei Zhang¹, Weijun Chen^{4

12}, Shida Zhu^{1

13}, Xun Xu^{1

14}, Xin Jin¹, Jingxian Zhao³, Nanshan Zhong³, Wenwei Zhang¹, Jincun Zhao^{3

5}, Junhua Li^{1

2

6}, Yonghao Xu³

Affiliations

¹ BGI-Shenzhen, Shenzhen, China.
² Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, Shenzhen, China.
³ State 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, China.
⁴ BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China.
⁵ Institute of Infectious Disease, Guangzhou Eighth People's Hospital of Guangzhou Medical University, Guangzhou, China.
⁶ School of Biology and Biological Engineering, South China University of Technology, Guangzhou, China.
⁷ Guangdong Provincial Key Laboratory of Biomedical Imaging, Department of Infectious Diseases, Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, China.
⁸ The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, China.
⁹ Yangjiang People's Hospital, Yangjiang, China.
¹⁰ Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
¹¹ Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, BGI-Shenzhen, Shenzhen, China.
¹² BGI PathoGenesis Pharmaceutical Technology, BGI-Shenzhen, Shenzhen, China.
¹³ Shenzhen Engineering Laboratory for Innovative Molecular Diagnostics, BGI-Shenzhen, Shenzhen, China.
¹⁴ Guangdong Provincial Key Laboratory of Genome Read and Write, BGI-Shenzhen, Shenzhen, China.

Abstract

The emergence of the novel human coronavirus, SARS-CoV-2, causes a global COVID-19 (coronavirus disease 2019) pandemic. Here, we have characterized and compared viral populations of SARS-CoV-2 among COVID-19 patients within and across households. Our work showed an active viral replication activity in the human respiratory tract and the co-existence of genetically distinct viruses within the same host. The inter-host comparison among viral populations further revealed a narrow transmission bottleneck between patients from the same households, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions.

Keywords: SARS-CoV-2; evolution; human to human transmission; intra-host variation; population bottleneck.