The coronavirus disease 2019 (COVID-19) outbreak, caused by SARS-CoV-2, has rapidly expanded to a global pandemic. However, numbers of infected cases, deaths, and mortality rates related to COVID-19 vary from country to country. Although many studies were conducted, the reasons of these differences have not been clarified. In this study, we comprehensively investigated 12,343 SARS-CoV-2 genome sequences isolated from patients/individuals in six geographic areas and identified a total of 1234 mutations by comparing with the reference SARS-CoV-2 sequence. Through a hierarchical clustering based on the mutant frequencies, we classified the 28 countries into three clusters showing different fatality rates of COVID-19. In correlation analyses, we identified that ORF1ab 4715L and S protein 614G variants, which are in a strong linkage disequilibrium, showed significant positive correlations with fatality rates ( r = 0.41, P = 0.029 and r = 0.43, P = 0.022, respectively). We found that BCG-vaccination status significantly associated with the fatality rates as well as number of infected cases. In BCG-vaccinated countries, the frequency of the S 614G variant had a trend of association with the higher fatality rate. We also found that the frequency of several HLA alleles, including HLA-A*11:01 , were significantly associated with the fatality rates, although these factors were associated with number of infected cases and not an independent factor to affect fatality rate in each country. Our findings suggest that SARS-CoV-2 mutations as well as BCG-vaccination status and a host genetic factor, HLA genotypes might affect the susceptibility to SARS-CoV-2 infection or severity of COVID-19.
【저자키워드】 Infection, Immunogenetics, 【초록키워드】 COVID-19, coronavirus disease, SARS-CoV-2, Mutation, S protein, SARS-COV-2 infection, susceptibility, Genetic, variant, variants, global pandemic, outbreak, severity of COVID-19, Genotype, Clustering, Cluster, HLA, mutant, mortality rate, SARS-CoV-2 mutation, correlation, association, fatality, Frequency, Linkage disequilibrium, ORF1ab, deaths, Hierarchical, Factor, frequencies, positive correlation, HLA alleles, SARS-CoV-2 sequence, Fatality rate, infected cases, SARS-CoV-2 genome sequence, Host, Affect, country, independent, caused, significantly, investigated, conducted, analyses, number of infected, 【제목키워드】 COVID-19, SARS-CoV-2, mortality rate, genomic variation,