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

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

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. Author summary In this study, we compared SARS-CoV-2 populations of 13 Chinese COVID-19 patients. Those viral populations contained a considerable proportion of viral sub-genomic messenger RNAs (sgmRNA), reflecting an active viral replication activity in the respiratory tract tissues. The comparison of 66 identified intra-host variants further showed a low viral genetic distance between intra-household patients and a narrow transmission bottleneck size. Despite the co-existence of genetically distinct viruses within the same host, most intra-host minor variants were not shared between transmission pairs, suggesting a dominated role of stochastic dynamics in both inter-host and intra-host evolutions. Furthermore, the narrow bottleneck and active viral activity in the respiratory tract show that the passage of a small number of virions can cause infection. Our data have therefore delivered a key genomic resource for the SARS-CoV-2 transmission research and enhanced our understanding of the evolutionary dynamics of SARS-CoV-2.