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

Abstract

In response to the current COVID-19 pandemic, it is crucial to understand the origin, transmission, and evolution of 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 COVID-19 patients 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 evolving 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 distinct pattern of frequency changes in different individuals, indicating a strong random drift. In summary, dramatic changes of 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.

Genetic Diversity of SARS-CoV-2 over a One-Year Period of the COVID-19 Pandemic: A Global Perspective

“…The P323L variant might alter the secondary and tertiary structures of NSP12 to interact with NSP8, thereby affecting viral replication [ 62 , 63 ]. Additionally, other variants like S25L in NSP7, S194L, R203K, G204R, and T205I in nucleocapsid, T85I and I120F in NSP2, S477N in spike, and Q57H in ORF3a have also been confirmed by previous studies [ 62 , 64 ]. Although many SARS-CoV-2 variants have been observed, their associations with viral loads and infectivity need more investigation.…”

Isolation of Viable SARS-CoV-2 Virus from Feces of an Immunocompromised Patient Suggesting a Possible Fecal Mode of Transmission

“…Genome sequence differences were probably not related to subcultures as the comparison of more than 50 SARS-CoV-2 full-length genomes sequenced in our laboratory showed no significant differences between the sequences from isolates or samples. Genome sequences of the two strains were sufficiently different to hypothesize a dual SARS-CoV-2 infection as it has already been reported [ 18 , 19 ], rather than genome variants related to ongoing evolution of SARS-CoV-2 in the human body [ 20 ].…”

COVID-19 mRNA vaccines

“…SARS-CoV-2 was initially identified as the etiologic agent responsible for an outbreak of pneumonia cases in late December 2019( Juno et al, 2020 ; Shan et al, 2020 ; Sun et al, 2020 ; Xu et al, 2020 ; Zhou et al, 2020 ; Zhu et al, 2020c ). On March 11 th , 2020, the World Health Organization (WHO) declared SARS-CoV-2 a global pandemic, and the disease was named the coronavirus disease 2019 (COVID-19)( Juno et al, 2020 ).…”