Genomic Epidemiology of CVA10 in Guangdong, China, 2013-2021

Abstract Hand, Foot and Mouth Disease (HFMD) is a highly contagious viral illness that primarily affects children globally. A significant epidemiological transition has been noted in mainland China, characterized by a substantial increase in HFMD cases caused by non-EV-A71 and non-CVA6 enteroviruses. Our study undertakes a retrospective examination of 36,461 enterovirus-positive specimens collected from Guangdong, China, from 2013 to 2021. Epidemiological trends suggest that, following 2013, CVA6 and CVA10 have risen to be the primary etiological agents for HFMD. In stark contrast, the incidence of EV-A71 has sharply declined, nearing extinction after 2018. Notably, CVA10 infection cases were considerably younger, with a median age of 1.8 years, compared to 2.3 years for those with EV-A71 infections, which may correlate with accumulated EV-A71-specific herd immunity among young children. Through extensive genomic sequencing and analysis, we identified the N136D mutation in the 2A protein, contributing to a predominant subcluster within genogroup C of CVA10 that has been circulating in Guangdong since 2017. Additionally, a high frequency of recombination events was observed in genogroup F of CVA10, suggesting that the prevalence of this lineage might be underrecognized. The dynamic landscape of enterovirus genotypes, along with their potential to cause outbreaks, underscores the need to broaden surveillance efforts to include a more diverse spectrum of enterovirus genotypes. Moreover, considering the shifting dominance of enterovirus genotypes, it may be prudent to re-evaluate and optimize existing vaccination strategies, which are currently focused primarily on EV-A71.