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
{"title":"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","authors":"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","doi":"10.1186/s12976-021-00140-3","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>We estimated the instantaneous transmissibility of COVID-19 by using the time-varying reproduction number (R<sub>t</sub>). 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 R<sub>t</sub>. We adopted the COVID-19 surveillance data in California as an example for demonstration.</p><p><strong>Results: </strong>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 R<sub>t</sub>, which explains 61% of the R<sub>t</sub> variation after accounting for the control measures. We remark that the modeling framework can be extended to study other infectious pathogens.</p><p><strong>Conclusions: </strong>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 R<sub>t</sub>. Future studies exploring the mechanism between SARS-CoV-2 mutations and COVID-19 infectivity are warranted.</p>","PeriodicalId":75215,"journal":{"name":"","volume":"18 1","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2021-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/s12976-021-00140-3","citationCount":"9","resultStr":"{\"title\":\"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.\",\"authors\":\"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\",\"doi\":\"10.1186/s12976-021-00140-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>We estimated the instantaneous transmissibility of COVID-19 by using the time-varying reproduction number (R<sub>t</sub>). 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 R<sub>t</sub>. We adopted the COVID-19 surveillance data in California as an example for demonstration.</p><p><strong>Results: </strong>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 R<sub>t</sub>, which explains 61% of the R<sub>t</sub> variation after accounting for the control measures. We remark that the modeling framework can be extended to study other infectious pathogens.</p><p><strong>Conclusions: </strong>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 R<sub>t</sub>. Future studies exploring the mechanism between SARS-CoV-2 mutations and COVID-19 infectivity are warranted.</p>\",\"PeriodicalId\":75215,\"journal\":{\"name\":\"\",\"volume\":\"18 1\",\"pages\":\"10\"},\"PeriodicalIF\":0.0,\"publicationDate\":\"2021-03-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1186/s12976-021-00140-3\",\"citationCount\":\"9\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1186/s12976-021-00140-3\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1186/s12976-021-00140-3","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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.