tetano
Editor, Senior Moderator
Genome Med
. 2021 Feb 22;13(1):30.
doi: 10.1186/s13073-021-00847-5.
Intra-host variation and evolutionary dynamics of SARS-CoV-2 populations in COVID-19 patients
Yanqun Wang[SUP] #[/SUP][SUP] 1 [/SUP], Daxi Wang[SUP] #[/SUP][SUP] 2 3 [/SUP], Lu Zhang[SUP] #[/SUP][SUP] 4 [/SUP], Wanying Sun[SUP] #[/SUP][SUP] 2 3 5 [/SUP], Zhaoyong Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Weijun Chen[SUP] #[/SUP][SUP] 5 6 [/SUP], Airu Zhu[SUP] #[/SUP][SUP] 1 [/SUP], Yongbo Huang[SUP] #[/SUP][SUP] 1 [/SUP], Fei Xiao[SUP] 7 [/SUP], Jinxiu Yao[SUP] 8 [/SUP], Mian Gan[SUP] 1 [/SUP], Fang Li[SUP] 1 [/SUP], Ling Luo[SUP] 1 [/SUP], Xiaofang Huang[SUP] 1 [/SUP], Yanjun Zhang[SUP] 1 [/SUP], Sook-San Wong[SUP] 1 [/SUP], Xinyi Cheng[SUP] 2 9 [/SUP], Jingkai Ji[SUP] 2 3 10 [/SUP], Zhihua Ou[SUP] 2 3 [/SUP], Minfeng Xiao[SUP] 2 3 [/SUP], Min Li[SUP] 2 3 5 [/SUP], Jiandong Li[SUP] 2 3 5 [/SUP], Peidi Ren[SUP] 2 3 [/SUP], Ziqing Deng[SUP] 2 3 [/SUP], Huanzi Zhong[SUP] 2 3 [/SUP], Xun Xu[SUP] 2 11 [/SUP], Tie Song[SUP] 12 [/SUP], Chris Ka Pun Mok[SUP] 1 13 [/SUP], Malik Peiris[SUP] 1 13 [/SUP], Nanshan Zhong[SUP] 1 [/SUP], Jingxian Zhao[SUP] 14 [/SUP], Yimin Li[SUP] 15 [/SUP], Junhua Li[SUP] 16 17 18 [/SUP], Jincun Zhao[SUP] 19 20 [/SUP]
Affiliations
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.
Keywords: COVID-19; Dynamics; Intra-host; SARS-CoV-2; Variation.
. 2021 Feb 22;13(1):30.
doi: 10.1186/s13073-021-00847-5.
Intra-host variation and evolutionary dynamics of SARS-CoV-2 populations in COVID-19 patients
Yanqun Wang[SUP] #[/SUP][SUP] 1 [/SUP], Daxi Wang[SUP] #[/SUP][SUP] 2 3 [/SUP], Lu Zhang[SUP] #[/SUP][SUP] 4 [/SUP], Wanying Sun[SUP] #[/SUP][SUP] 2 3 5 [/SUP], Zhaoyong Zhang[SUP] #[/SUP][SUP] 1 [/SUP], Weijun Chen[SUP] #[/SUP][SUP] 5 6 [/SUP], Airu Zhu[SUP] #[/SUP][SUP] 1 [/SUP], Yongbo Huang[SUP] #[/SUP][SUP] 1 [/SUP], Fei Xiao[SUP] 7 [/SUP], Jinxiu Yao[SUP] 8 [/SUP], Mian Gan[SUP] 1 [/SUP], Fang Li[SUP] 1 [/SUP], Ling Luo[SUP] 1 [/SUP], Xiaofang Huang[SUP] 1 [/SUP], Yanjun Zhang[SUP] 1 [/SUP], Sook-San Wong[SUP] 1 [/SUP], Xinyi Cheng[SUP] 2 9 [/SUP], Jingkai Ji[SUP] 2 3 10 [/SUP], Zhihua Ou[SUP] 2 3 [/SUP], Minfeng Xiao[SUP] 2 3 [/SUP], Min Li[SUP] 2 3 5 [/SUP], Jiandong Li[SUP] 2 3 5 [/SUP], Peidi Ren[SUP] 2 3 [/SUP], Ziqing Deng[SUP] 2 3 [/SUP], Huanzi Zhong[SUP] 2 3 [/SUP], Xun Xu[SUP] 2 11 [/SUP], Tie Song[SUP] 12 [/SUP], Chris Ka Pun Mok[SUP] 1 13 [/SUP], Malik Peiris[SUP] 1 13 [/SUP], Nanshan Zhong[SUP] 1 [/SUP], Jingxian Zhao[SUP] 14 [/SUP], Yimin Li[SUP] 15 [/SUP], Junhua Li[SUP] 16 17 18 [/SUP], Jincun Zhao[SUP] 19 20 [/SUP]
Affiliations
- PMID: 33618765
- DOI: 10.1186/s13073-021-00847-5
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.
Keywords: COVID-19; Dynamics; Intra-host; SARS-CoV-2; Variation.