Updated SARS‐CoV‐2 single nucleotide variants and mortality association

By analyzing newly collected SARS‐CoV‐2 genomes and comparing them with our previous study about SARS‐CoV‐2 single nucleotide variants (SNVs) before June 2020, we found that the SNV clustering had changed remarkably since June 2020. Apart from that the group of SNVs became dominant, which is represented by two nonsynonymous mutations A23403G (S:D614G) and C14408T (ORF1ab:P4715L), a few emerging groups of SNVs were recognized with sharply increased monthly incidence ratios of up to 70% in November 2020. Further investigation revealed sets of SNVs specific to patients' ages and/or gender, or strongly associated with mortality. Our logistic regression model explored features contributing to mortality status, including three critical SNVs, G25088T(S:V1176F), T27484C (ORF7a:L31L), and T25A (upstream of ORF1ab), ages above 40 years old, and the male gender. The protein structure analysis indicated that the emerging subgroups of nonsynonymous SNVs and the mortality‐related ones were located on the protein surface area. The clashes in protein structure introduced by these mutations might in turn affect the viral pathogenesis through the alteration of protein conformation, leading to a difference in transmission and virulence. Particularly, we explored the fact that nonsynonymous SNVs tended to occur in intrinsic disordered regions of Spike and ORF1ab to significantly increase hydrophobicity, suggesting a potential role in the change of protein folding related to immune evasion. Key Points There has been a considerable temporal change of the SARS‐CoV‐2 single nucleotide variants (SNVs) clustering since June 2020. Apart from one group of SNVs that became dominant, a few emerging groups of SNVs were recognized with sharply increased monthly occurrence ratios in November 2020. All of these individual SNVs could be traced back to February or March of 2020 when they were identified for the first time, suggesting a potential incubation period of the collectivity of special groups of SNVs. 114 age‐specific SNVs were identified in one or across multiple age groups. 42 SNVs showed significantly high rates in either males or females. 41 and 30 SNVs were observed with at least twofold higher incidence rates in the death and the nondeath group, respectively. A logistic regression model demonstrated that three critical SNVs, G25088T(S:V1176F), T27484C (ORF7a:L31L), and T25A (upstream of ORF1ab), ages above 40 years old, and the male group contribute to a relatively higher morta