Dynamics of severe acute respiratory syndrome coronavirus 2 genome variants in the feces during convalescence.

Dynamics of severe acute respiratory syndrome coronavirus 2 genome variants in the feces during convalescence.
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DOI:
10.1016/j.jgg.2020.10.002
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发表时间:
2020-10-20
期刊:
Journal of genetics and genomics = Yi chuan xue bao
影响因子:
--
通讯作者:
Li M
Li M
中科院分区:
其他
文献类型:
--
作者:
Xu Y;Kang L;Shen Z;Li X;Wu W;Ma W;Fang C;Yang F;Jiang X;Gong S;Zhang L;Li M

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为应对当前的2019冠状病毒病(COVID-19)大流行,了解严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)的起源、传播和进化至关重要,这依赖于对临床样本基因组多样性的密切监测。尽管在群体水平上的突变已被广泛研究,但突变如何在个体水平上进化在很大程度上是未知的。收集9例COVID-19恢复期患者18份时间序列粪便样本。采用杂交捕获法富集SARS-CoV-2核酸。首先,我们证明了混合捕获方法在检测宿主内变异方面的卓越性能。我们在18份粪便样本的182个位点鉴定出229种宿主内变异。其中19个变异在1-5天内出现频率变化> 0.3,反映了宿主内病毒种群的高度动态。此外,病毒基因组的进化表明病毒在恢复期可能在胃肠道中存活。同时,我们还发现同一突变在不同个体中表现出明显的频率变化模式,表明有很强的随机漂移。综上所述,在恢复期粪便样本中检测到SARS-CoV-2基因组的显著变化;粪便中的病毒载量是否足以确定感染值得进一步调查。
In response to the current coronavirus disease 2019 (COVID-19) pandemic, it is crucial to understand the origin, transmission, and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which relies on close surveillance of genomic diversity in clinical samples. Although the mutation at the population level had been extensively investigated, how the mutations evolve at the individual level is largely unknown. Eighteen time-series fecal samples were collected from nine patients with COVID-19 during the convalescent phase. The nucleic acids of SARS-CoV-2 were enriched by the hybrid capture method. First, we demonstrated the outstanding performance of the hybrid capture method in detecting intra-host variants. We identified 229 intra-host variants at 182 sites in 18 fecal samples. Among them, nineteen variants presented frequency changes > 0.3 within 1–5 days, reflecting highly dynamic intra-host viral populations. Moreover, the evolution of the viral genome demonstrated that the virus was probably viable in the gastrointestinal tract during the convalescent period. Meanwhile, we also found that the same mutation showed a distinct pattern of frequency changes in different individuals, indicating a strong random drift. In summary, dramatic changes of the SARS-CoV-2 genome were detected in fecal samples during the convalescent period; whether the viral load in feces is sufficient to establish an infection warranted further investigation.
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