Among a cluster of COVID-19 cases from the end of March through April 2021 in Asahikawa, we experienced the cases in which patients manifested severe clinical symptoms compared to patients who were infected before that. A hundred three patients (age range: 65 to 89 years old) enrolled in this study were divided into two groups, group A: the patients infected from November 2020 to March 2021, and group B: the patients in this cluster population. The mortality rates were 6.1% in group A and 16.2% in group B (OR: 2.97, 95%CI: 0.65-15.38). For the severity of disease, the patients in group B required higher oxygen flow rate in early course of admission (mild; p=0.892, moderate; p=0.117, severe; p=0.029). Whole viral genome sequences revealed five non-synonymous mutations by comparison of the isolates with each group. Of these, four were on non-structural proteins (NSPs) including nsp3, 6 and 15, and one was on S protein located near the C-terminus, suggesting that the mutations on NSPs could be responsible for adverse clinical outcomes in COVID-19 patients.
