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.
【저자키워드】 COVID-19, Mutation, Transmission, Spike protein, Statistical modeling, 【초록키워드】 SARS-CoV-2, COVID-19 pandemic, Variation, Spike protein, global health, Prevalence, Health, Measures, Transmissibility, disease control, SARS-CoV-2 spike protein, Reproduction number, Pathogens, SARS-CoV-2 mutations, SARS-CoV-2 mutation, disease, mechanism, association, Amino acid, Evidence, Frequency, amino acid substitutions, glycine, supplementary material, 95% CI, pathogenic mutations, sequence, Substitution, demonstration, codon, surveillance data, positive, D614G substitution, statistical framework, amino acid substitution, Future, approach, Result, example, adopted, increase in, explain, quantified, instantaneous, pathogenic mutation, the SARS-CoV-2, 【제목키워드】 Transmissibility, SARS-CoV-2 spike, association, surveillance data, example,