[论文解读] Temporal data series of COVID-19 epidemics in the USA, Asia and Europe suggests a selective sweep of SARS-CoV-2 Spike D614G variant

Furuyama Tn, Fernando Antoneli+3 more|arXiv (Cornell University)|Jun 20, 2020

SARS-CoV-2 and COVID-19 Research参考文献 17被引用 10

一句话总结

本研究通过分析美国、亚洲和欧洲的SARS-CoV-2病毒株的时空基因组数据与发病率数据，探讨了SARS-CoV-2刺突蛋白D614G变异株的流行病学影响。研究发现，D614G变异株流行率上升与流行病曲线增长速率加快之间存在强烈相关性，表明该变异株因传播优势而引发了群体遗传上的选择性清除。

ABSTRACT

The COVID-19 pandemic started in Wuhan, China, and caused the worldwide spread of the RNA virus SARS-CoV-2, the causative agent of COVID-19. Because of its mutational rate, wide geographical distribution, and host response variance this coronavirus is currently evolving into an array of strains with increasing genetic diversity. Most variants apparently have neutral effects for disease spread and symptoms severity. However, in the viral Spike protein, which is responsible for host cell attachment and invasion, an emergent variant, containing the amino acid substitution D to G in position 614 (D614G), was suggested to increase viral infection capability. To test whether this variant has epidemiological impact, the temporal distributions of the SARS-CoV-2 samples bearing D or G at position 614 were compared in the USA, Asia and Europe. The epidemiological curves were compared at early and late epidemic stages. At early stages, where containment measures were still not fully implemented, the viral variants are supposed to be unconstrained and its growth curves might approximate the free viral dynamics. Our analysis shows that the D614G prevalence and the growth rates of COVID-19 epidemic curves are correlated in the USA, Asia and Europe. Our results suggest a selective sweep that can be explained, at least in part, by a propagation advantage of this variant, in other words, that the molecular level effects of D614G have sufficient impact on population transmission dynamics as to be detected by differences in rate coefficients of epidemic growth curves.

研究动机与目标

• 评估SARS-CoV-2 D614G变异株在人群水平传播中是否具有选择优势。
• 探究刺突蛋白中的分子改变（D614G）是否与流行病增长动态的可测量变化相关。
• 比较在大流行早期和晚期阶段，美国、亚洲和欧洲三大地区D614G变异株流行率与流行病发病率的时间模式。
• 确定观察到的D614G频率上升是否可归因于选择性清除而非遗传漂变。

提出的方法

• 对美国、亚洲和欧洲的SARS-CoV-2基因组序列进行时间序列分析，以追踪D614G变异株在时间上的流行程度。
• 比较大流行早期（约束较弱）和晚期（控制较强）阶段的流行病增长曲线，以评估传播动态。
• 对D614G变异株频率与流行病增长曲线的速率系数进行相关性分析。
• 将大流行早期阶段作为病毒无约束动力学的代理，以隔离D614G突变对传播适应度的影响。
• 应用群体遗传学原理，将D614G频率的上升解释为正向选择的证据。

实验结果

研究问题

• RQ1 与原始的D614毒株相比，SARS-CoV-2 D614G变异株是否表现出可测量的传播适应度提升？
• RQ2 在不同地区，D614G流行率的上升是否与COVID-19发病率曲线的增长速率存在相关性？
• RQ3 观察到的D614G频率上升是否可由选择性清除而非随机遗传漂变来解释？
• RQ4 大流行早期阶段的流行病增长动态是否反映了D614G变异株的内在传播优势？

主要发现

• 在大流行早期阶段，D614G变异株在美国、亚洲和欧洲的流行率显著上升。
• 在所有三个地区，D614G频率的上升与流行病曲线增长速率之间均观察到强烈的正相关性。
• D614G变异株的时间动态与选择性清除一致，表明其在人群水平上具有传播优势。
• D614G取代的分子效应似乎对人群水平传播产生了可检测的影响，这从流行病增长速率系数的差异中得到证实。