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.

为了应对当前的 2019 年冠状病毒病 (COVID-19) 大流行，了解严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 的起源、传播和进化至关重要，这依赖于对基因组多样性的密切监测在临床样本中。尽管对群体水平的突变进行了广泛的研究，但突变在个体水平上如何进化仍然未知。从 9 名 COVID-19 恢复期患者身上收集了 18 个时间序列粪便样本。通过混合捕获方法富集了 SARS-CoV-2 的核酸。首先，我们展示了混合捕获方法在检测宿主内变异方面的出色性能。我们在 18 个粪便样本的 182 个位点鉴定出了 229 个宿主内变异。其中，19 个变体在 1-5 天内频率变化 > 0.3，反映了宿主内病毒群体的高度动态。此外，病毒基因组的进化表明，该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，表明存在很强的随机漂移。综上所述，在恢复期的粪便样本中检测到了 SARS-CoV-2 基因组的巨大变化；粪便中的病毒载量是否足以建立感染，需要进一步调查。