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.

由SARS-CoV-2引起的2019年冠状病毒疾病（COVID-19）爆发已迅速扩大到全球大流行。但是，与COVID-19相关的感染病例数，死亡人数和死亡率因国家而异。尽管进行了许多研究，但尚不清楚这些差异的原因。在这项研究中，我们全面研究了在六个地理区域从患者/个人中分离出的12,343个SARS-CoV-2基因组序列，并与参考SARS-CoV-2序列进行了比较，共鉴定出1234个突变。通过基于突变频率的分层聚类，我们将28个国家分为三个显示COVID-19死亡率不同的聚类。在相关性分析中，我们确定了ORF1ab 4715L和S蛋白614G变体处于强烈的连锁不平衡状态，r  = 0.41，P  = 0.029，r  = 0.43，P  = 0.022）。我们发现，卡介苗的接种状况与死亡率和感染病例数显着相关。在接种过卡介苗的国家中，S 614G变异的发生率与死亡率较高相关。我们还发现，包括HLA-A * 11：01在内的多个HLA等位基因的频率与致死率显着相关，尽管这些因素与受感染病例的数量有关，而不是影响每个国家致死率的独立因素。我们的发现表明，SARS-CoV-2突变以及BCG疫苗接种状况和宿主遗传因素，HLA基因型可能会影响SARS-CoV-2感染的易感性或COVID-19的严重性。