Genetic Characteristics and Phylogenetic Analysis of Coxsackievirus A6 Isolated in Linyi, China, 2022-2023

Hand, foot, and mouth disease (HFMD) has become one of the most common infectious diseases in the past few decades. Since 2013, coxsackievirus A6 (CVA6) has replaced enterovirus A71 (EV-A71) and coxsackievirus A16 (CVA16), becoming the predominant pathogen responsible for HFMD in many areas of China. This study aimed to investigate the genetic characteristics and molecular epidemiology of CVA6 in Linyi between the years 2022 and 2023. In total, 965 patients with HFMD were enrolled in this study, and analyses based on VP1 nucleotide sequences were performed to determine the evolutionary trajectory of CVA6. In 2022, 281/386 (72.8%) patients were positive for enteroviruses (EVs) and 217/281 (77.2%) were CVA6 positive. In 2023, 398/579 (68.7%) samples were positive for EVs and 243/398 (61.1%) were CVA6 positive. Six sequences were selected each year for homology analysis. The results showed that the 12 strains isolated from Linyi were distant from the prototype strain (AY421764) and the first CVA6 strain reported in China (JQ364886). Phylogenetic analysis showed that the CVA6 strains isolated from Linyi belonged to the D3 sub-genotype. CVA6 is emerging as a common pathogen causing HFMD in Linyi and continuous surveillance of HFMD etiologies agents is necessary.