Mutations in the non-structural proteins of SARS-CoV-2 may contribute to adverse clinical outcome in COVID-19 patients

ABSTRACT

Background . From late March through April 2021, we experienced a cluster of COVID-19 patients, named “Cluster K”, with rapid severe illness compared to those who were infected before. Method . COVID-19 patients enrolled in this study were divided into two groups 66 patients from November 2020 to March 2021(group A), 37 patients whose infection links were traced from Cluster K (group B). The primary outcome was mortality rate, and the secondary outcome was maximal oxygen flow rate as severity of the disease. Viral genome sequences were compared between two groups. Results . Mortality rates were 6.1% in group A and 16.2% in group B (OR 2.97, 95%CI 0.65-15.38). The patients in group B required high oxygen flow rate (O2 ≥10 L/min) in earlier clinical course (p=0.029). Viral genome sequences revealed five amino acid mutations. Of these, four were found on three non-structural proteins (NSPs) one in nsp3 and 15, two in nsp6 (one of them is near the potential sites under positive selective pressure). Other one was on S protein. Conclusion . This study suggests that mutations in NSPs, especially nsp6, are associated with adverse clinical outcome in COVID-19 patients.