Genome Medicine (Feb 2021)

Intra-host variation and evolutionary dynamics of SARS-CoV-2 populations 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,
  • Xun Xu,
  • Tie Song,
  • Chris Ka Pun Mok,
  • Malik Peiris,
  • Nanshan Zhong,
  • Jingxian Zhao,
  • Yimin Li,
  • Junhua Li,
  • Jincun Zhao

DOI
https://doi.org/10.1186/s13073-021-00847-5
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 13

Abstract

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Abstract Background Since early February 2021, the causative agent of COVID-19, SARS-CoV-2, has infected over 104 million people with more than 2 million deaths according to official reports. 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. Methods Using high-throughput sequencing of metatranscriptomic and hybrid captured libraries, we characterized consensus genomes and intra-host single nucleotide variations (iSNVs) of serial samples collected from eight patients with COVID-19. The distribution of iSNVs along the SARS-CoV-2 genome was analyzed and co-occurring iSNVs among COVID-19 patients were identified. We also compared the evolutionary dynamics of SARS-CoV-2 population in the respiratory tract (RT) and gastrointestinal tract (GIT). Results The 32 consensus genomes revealed the co-existence of different genotypes within the same patient. We further identified 40 intra-host single nucleotide variants (iSNVs). Most (30/40) iSNVs presented in a single patient, while ten iSNVs were found in at least two patients or identical to consensus variants. Comparing allele frequencies of the iSNVs revealed a clear genetic differentiation between intra-host populations from the respiratory tract (RT) and gastrointestinal tract (GIT), mostly driven by bottleneck events during intra-host migrations. Compared to RT populations, the GIT populations showed a better maintenance and rapid development of viral genetic diversity following the suspected intra-host bottlenecks. Conclusions Our findings here illustrate the intra-host bottlenecks and evolutionary dynamics of SARS-CoV-2 in different anatomic sites and may provide new insights to understand the virus-host interactions of coronaviruses and other RNA viruses.

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