The COVID-19 pandemic poses a serious threat to global health, and pathogenic mutations are a major challenge to disease control. We developed a statistical framework to explore the association between molecular-level mutation activity of SARS-CoV-2 and population-level disease transmissibility of COVID-19. We estimated the instantaneous transmissibility of COVID-19 by using the time-varying reproduction number (Rt). The mutation activity in SARS-CoV-2 is quantified empirically depending on (i) the prevalence of emerged amino acid substitutions and (ii) the frequency of these substitutions in the whole sequence. Using the likelihood-based approach, a statistical framework is developed to examine the association between mutation activity and Rt. We adopted the COVID-19 surveillance data in California as an example for demonstration. We found a significant positive association between population-level COVID-19 transmissibility and the D614G substitution on the SARS-CoV-2 spike protein. We estimate that a per 0.01 increase in the prevalence of glycine (G) on codon 614 is positively associated with a 0.49% (95% CI: 0.39 to 0.59) increase in Rt, which explains 61% of the Rt variation after accounting for the control measures. We remark that the modeling framework can be extended to study other infectious pathogens. Our findings show a link between the molecular-level mutation activity of SARS-CoV-2 and population-level transmission of COVID-19 to provide further evidence for a positive association between the D614G substitution and Rt. Future studies exploring the mechanism between SARS-CoV-2 mutations and COVID-19 infectivity are warranted.

中文翻译：

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对 COVID-19 传播性与 SARS-CoV-2 刺突蛋白中 D614G 替代之间的关联进行建模：以加利福尼亚州的监测数据为例

COVID-19大流行对全球健康构成严重威胁，致病突变是疾病控制的重大挑战。我们开发了一个统计框架来探索 SARS-CoV-2 的分子水平突变活性与 COVID-19 的人群水平疾病传播率之间的关联。我们使用随时间变化的传染数 (Rt) 估计了 COVID-19 的瞬时传播率。SARS-CoV-2 中的突变活性根据 (i) 出现的氨基酸取代的发生率和 (ii) 整个序列中这些取代的频率进行经验量化。使用基于可能性的方法，开发了一个统计框架来检查突变活性和 Rt 之间的关联。我们以加州的COVID-19监测数据为例进行演示。我们发现人群层面的 COVID-19 传播率与 SARS-CoV-2 刺突蛋白上的 D614G 取代之间存在显着的正相关关系。我们估计，密码子 614 上甘氨酸 (G) 的流行率每增加 0.01，与 Rt 增加 0.49%（95% CI：0.39 至 0.59）呈正相关，这解释了在考虑了控制措施。我们指出，模型框架可以扩展到研究其他传染性病原体。我们的研究结果显示了 SARS-CoV-2 的分子水平突变活性与 COVID-19 的人群水平传播之间的联系，为 D614G 替代与 Rt 之间的正相关性提供了进一步的证据。未来有必要进行探索 SARS-CoV-2 突变与 COVID-19 感染性之间机制的研究。