Exploring the Interaction between E484K and N501Y Substitutions of SARS-CoV-2 in Shaping the Transmission Advantage of COVID-19 in Brazil: A Modeling Study

The COVID-19 pandemic poses serious threats to global health, and the emerging mutation in SARS-CoV-2 genomes is one of the major challenges of disease control. Considering the growth of epidemic curve and the circulating SARS-CoV-2 variants in Brazil, the role of locally prevalent E484K and N501Y substitutions in contributing to the epidemiological outcomes is of public health interest for investigation. We developed a likelihood-based statistical framework to reconstruct reproduction numbers, estimate transmission advantage associated with different SARS-CoV-2 variants regarding the marking (identifying) 484K and 501Y substitutions (including Alpha, Zeta, and Gamma variants) in Brazil, and explored the interactive effects of genetic activities on transmission advantage marked by these two mutations. We found a significant transmission advantage associated with the 484K/501Y variants (including P.1 or Gamma variants), which increased the infectivity significantly by 23%. In contrast and by comparison to Gamma variants, E484K or N501Y (including Alpha or Zeta variants) substitution alone appeared less likely to secure a concrete transmission advantage in Brazil. Our finding indicates that the combined impact of genetic activities on transmission advantage marked by 484K/501Y outperforms their independent contributions in Brazil, which implies an interactive effect in shaping the increase in the infectivity of COVID-19. Future studies are needed to investigate the mechanisms of how E484K and N501Y mutations and the complex genetic mutation activities marked by them in SARS-CoV-2 affect the transmissibility of COVID-19.