模拟COVID-19传播率与SARS-CoV-2刺突蛋白D614G替代之间的关系:以加利福尼亚州的监测数据为例

Pub Date : 2021-03-09 DOI:10.1186/s12976-021-00140-3
Shi Zhao, Jingzhi Lou, Lirong Cao, Hong Zheng, Marc K C Chong, Zigui Chen, Benny C Y Zee, Paul K S Chan, Maggie H Wang
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引用次数: 9

摘要

背景:新冠肺炎大流行对全球健康构成严重威胁,致病性突变是疾病控制面临的重大挑战。我们建立了一个统计框架来探讨SARS-CoV-2分子水平突变活性与COVID-19人群水平疾病传播率之间的关系。方法:采用时变繁殖数(Rt)估计COVID-19的瞬时传播力。SARS-CoV-2的突变活性根据(i)出现的氨基酸取代的发生率和(ii)这些取代在整个序列中的频率进行经验量化。使用基于似然的方法,开发了一个统计框架来检查突变活性与rt之间的关联。我们以加利福尼亚州的COVID-19监测数据为例进行演示。结果:我们发现COVID-19在人群水平上的传播与SARS-CoV-2刺突蛋白上D614G的替换显著正相关。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,这解释了考虑控制措施后61%的Rt变化。我们注意到建模框架可以扩展到研究其他感染性病原体。结论:我们的研究结果表明,SARS-CoV-2的分子水平突变活性与COVID-19的人群水平传播之间存在联系,为D614G替代与rt之间的正相关提供了进一步的证据。未来有必要探索SARS-CoV-2突变与COVID-19传染性之间的机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Modelling the association between COVID-19 transmissibility and D614G substitution in SARS-CoV-2 spike protein: using the surveillance data in California as an example.

Modelling the association between COVID-19 transmissibility and D614G substitution in SARS-CoV-2 spike protein: using the surveillance data in California as an example.

Modelling the association between COVID-19 transmissibility and D614G substitution in SARS-CoV-2 spike protein: using the surveillance data in California as an example.

Modelling the association between COVID-19 transmissibility and D614G substitution in SARS-CoV-2 spike protein: using the surveillance data in California as an example.

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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