Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in late 2019 and caused the COVID-19 pandemic, has undergone genomic evolution, yielding variants of concern which include the Alpha, Delta, and Omicron variants. Since the virus continues to mutate, we designed this study to assess the impact of SARS-CoV-2 mutations on severity; using PLINK2 software, we analyzed genomic and clinical data from 310 hospitalized patients at the Institute of Science Tokyo Hospital. The analysis identified 64 statistically significant severity-associated mutations. Although the Omicron variants are generally associated with less severe symptoms than the Delta variants, our approach identified statistically significant Omicron variant-specific mutations that were associated with severe disease, as well as additional mutations for which the odds ratios and 95% confidence intervals indicated a consistent trend. Our retrospective analysis of SARS-CoV-2 genomic and clinical information may help clarify the biological significance of mutations.
石渡さおり et al. (2026) studied this question.