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Mutations on non-structural proteins of SARS-CoV-2 are possibly responsible for adverse clinical outcomes in a real-life practice

Among a single COVID-19 cluster population 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 reached to the clinical state which requires higher oxygen flow rate more quickly (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 NSPs including nsp3, 6 and 15, and one was on S protein located near the C-terminus, suggesting that mutations on NSPs could be responsible for adverse clinical outcomes in COVID-19 patients.