There is an urgent public health need to better understand Severe Acute Respiratory Syndrome (SARS)-CoV-2/COVID-19, particularly how sequences of the viruses could lead to diverse incidence and mortality of COVID-19 in different countries. However, because of its unknown ancestors and hosts, elucidating the genetic variations of the novel coronavirus, SARS-CoV-2, has been difficult. Without needing to know ancestors, we identified an uneven distribution of local genome similarities among the viruses categorized by geographic regions, and it was strongly correlated with incidence and mortality. To ensure unbiased and origin-independent analyses, we used a pairwise comparison of local genome sequences of virus genomes by Basic Local Alignment Search Tool (BLAST). We found a strong statistical correlation between dominance of the SARS-CoV-2 in distributions of uneven similarities and the incidence and mortality of illness. Genomic annotation of the BLAST hits also showed that viruses from geographic regions with severe infections tended to have more dynamic genomic regions in the SARS-CoV-2 receptor-binding domain (RBD) and receptor-binding motif (RBM) of the spike protein (S protein). Dynamic domains in the S protein were also confirmed by a canyon region of mismatches coincident with RBM and RBD, without hits of alignments of 100% matching. Thus, our origin-independent analysis suggests that the dynamic and unstable SARS-CoV-2-RBD could be the main reason for diverse incidence and mortality of COVID-19 infection.

中文翻译：

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独立起源分析将 SARS-CoV-2 局部基因组与 COVID-19 发病率和死亡率联系起来


公共卫生迫切需要更好地了解严重急性呼吸系统综合症 (SARS)-CoV-2/COVID-19，特别是病毒序列如何导致不同国家的 COVID-19 发病率和死亡率不同。然而，由于其祖先和宿主未知，阐明新型冠状病毒 SARS-CoV-2 的遗传变异一直很困难。无需了解祖先，我们就发现按地理区域分类的病毒之间局部基因组相似性分布不均匀，并且与发病率和死亡率密切相关。为了确保分析的公正性和起源无关性，我们通过基本局部比对搜索工具（BLAST）对病毒基因组的局部基因组序列进行了成对比较。我们发现 SARS-CoV-2 在不均匀相似性分布中的主导地位与疾病的发病率和死亡率之间存在很强的统计相关性。 BLAST 命中的基因组注释还表明，来自感染严重的地理区域的病毒往往在刺突蛋白的 SARS-CoV-2 受体结合域 (RBD) 和受体结合基序 (RBM) 中具有更动态的基因组区域。 S蛋白）。 S 蛋白中的动态结构域也通过与 RBM 和 RBD 一致的错配峡谷区域得到证实，没有 100% 匹配的比对命中。因此，我们的独立起源分析表明，动态且不稳定的 SARS-CoV-2-RBD 可能是 COVID-19 感染不同发病率和死亡率的主要原因。