Abstract
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.
Keywords: Dynamics; Hybrid capture; Intra-host variant; Mutation; SARS-CoV-2.
【저자키워드】 Mutation, Dynamics, Hybrid capture, SARS-CoV-2., Intra-host variant, 【초록키워드】 COVID-19, coronavirus disease, Evolution, SARS-CoV-2, Coronavirus disease 2019, coronavirus, pandemic, Mutation, Hybrid capture, variant, Infection, Transmission, severe acute respiratory syndrome Coronavirus, virus, clinical samples, nucleic acid, Viral, Surveillance, Viral load, nucleic acids, SARS-CoV-2 genome, feces, Fecal sample, respiratory, convalescent, genomic, change, gastrointestinal tract, Frequency, hybrid, Intra-host variant, viral genome, capture, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, convalescent phase, population level, intra-host variants, random, individual level, fecal samples, populations, collected, investigated, nine, changes in, demonstrated, individuals, patients with COVID-19, the SARS-CoV-2 genome, 【제목키워드】 coronavirus, respiratory, acute respiratory syndrome, genome variant,