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

Zhao, Shi; Lou, Jingzhi; Cao, Lirong; Zheng, Hong; Chong, Marc K. C.; Chen, Zigui; Zee, Benny C. Y.; Chan, Paul K. S.; Wang, Maggie H.

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 (R(t)). 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(t). 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 R(t), which explains 61% of the R(t) 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 R(t). Future studies exploring the mechanism between SARS-CoV-2 mutations and COVID-19 infectivity are warranted. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12976-021-00140-3.