Epidemiological and phylogenetic characterization of human respiratory syncytial virus associated with severe acute respiratory infections in paediatric patients from 2016 to 2023 in Hangzhou, China

Human respiratory syncytial virus (HRSV), a leading cause of paediatric respiratory infections, is a major contributor to global childhood morbidity. The primary objective of this study was to investigate the epidemiology and phylogenetic characterization of HRSV in paediatric severe acute respiratory infection (SARI) cases in Hangzhou. A total of 2,277 paediatric SARI samples were screened for HRSV. Epidemiological trends, including age-specific positivity rates, were analysed. Whole-genome sequencing was performed on 113 HRSV-positive samples (subgroup A <i>n</i>=60, subgroup B <i>n</i>=53) to characterize genetic evolution. Phylogenetic analysis identified viral lineages and evolutionary rates. <i>In silico</i> binding free energy calculations assessed the impact of antigenic site mutations on monoclonal antibody (mAb) binding. In this study, disruptions in transmission patterns and age-specific positivity rates were observed in 2021 and 2023, coinciding with strict COVID-19 non-pharmaceutical interventions. A novel A.D.3.X lineage, circulating during 2021-2023 and defined by five unique aa substitutions in the G gene, was identified. The emergence of this lineage may have contributed to the observed epidemiological disruptions. <i>In silico</i> binding free energy calculations predicted that antigenic site mutations (N276S and I206M) in local strains reduce binding affinities for mAbs motavizumab and nirsevimab. These results emphasize HRSV's genetic diversification in Eastern China and underscore the necessity for continuous genomic surveillance to track antigenic evolution and refine prevention strategies for high-risk paediatric populations.