Coxsackievirus A6 (CV-A6) has emerged as the predominant causative agent of hand, foot, and mouth disease (HFMD) in young children. Since the declaration of coronavirus disease 2019 (COVID-19) as a global pandemic, the incidence of infectious diseases, including HFMD, has decreased markedly. When social mitigation was relaxed during the COVID-19 pandemic in 2022, the re-emergence of HFMD was observed in Gwangju, South Korea, and seasonal characteristics of the disease appeared to have changed. To investigate the molecular characteristics of enterovirus (EV) associated with HFMD during 2022, 277 specimens were collected. Children aged younger than 5 years accounted for the majority of affected individuals. EV detection and genotyping were performed using real-time RT-PCR and nested RT-PCR followed by sequence analysis. The EV detection rate was found to be 82.3%, and the main genotype identified was CV-A6. Sixteen CV-A6 samples were selected for whole genome sequencing. According to phylogenetic analysis, all CV-A6 strains from this study belonged to the sub-genotype D3 clade based on VP1 sequences. Analysis of 3D polymerase phylogeny showed that only the recombinant RF-A group was identified. In conclusion, circulating EV types should be continuously monitored to understand pathogen emergence and evolution during the post-pandemic era.

Human adenoviruses (HAdVs) are important respiratory pathogens that circulate globally and frequently cause outbreaks, particularly among pediatric populations. Despite their clinical relevance, recent data on genome-wide evolution and recombination of circulating HAdVs in Korea remain limited. In this study, we characterized the epidemiological dynamics and genomic evolution of HAdVs detected in Gwangju, South Korea, between 2023 and 2025. Molecular epidemiological surveillance of respiratory samples was conducted, followed by phylogenetic and whole-genome sequencing analyses. Adenovirus positivity increased sharply during an outbreak from August to October 2023, with pediatric cases predominating. Phylogenetic analysis identified eight genotypes from species B and C, with genotype B114 as the principal outbreak strain. Whole-genome sequencing revealed recombination events in both species, involving antigenic, replication, and packaging regions. These findings indicate that circulating HAdVs undergo continuous genome-wide recombination, resulting in genotype-specific outbreaks that are not fully captured by capsid-based classification alone. Our study highlights the importance of whole-genome approaches for understanding adenovirus evolution and provides insights into the genomic diversity underlying recent outbreaks.

Lim MH, et al. J Korean Med Sci. 2026 Jun;41:e142. https://doi.org/10.3346/jkms.2026.41.e142

Coxsackievirus A6 (CV-A6) has emerged as the predominant causative agent of hand, foot, and mouth disease (HFMD) in young children. Since the declaration of coronavirus disease 2019 (COVID-19) as a global pandemic, the incidence of infectious diseases, including HFMD, has decreased markedly. When social mitigation was relaxed during the COVID-19 pandemic in 2022, re-emergence of HFMD was observed in Gwangju, South Korea, and seasonal characteristics of the disease appeared to have changed. To investigate the molecular characteristics of enterovirus (EV) associated with HFMD during 2022, 277 specimens were collected. Children aged under 5 years accounted for the majority of affected individuals. EV detection and genotyping were performed using real-time RT-PCR and nested RT-PCR followed by sequence analysis. EV detection rate was found to be 82.3%, and the main genotype identified was CV-A6. Sixteen CV-A6 samples were selected for whole genome sequencing. According to phylogenetic analysis, all CV-A6 strains from this study belonged to the sub-genotype D3 clade based on VP1 sequences. Analysis of 3D polymerase phylogeny showed that only the recombinant RF-A group was identified. In conclusion, circulating EV types should be continuously monitored to understand pathogen emergence and evolution during the post-pandemic era.