Genomic Diversity of Human Respiratory Syncytial Virus (HRSV) Type A in a Pediatric Cohort in the United States After the Onset of the COVID-19 Pandemic.

Human Respiratory Syncytial Virus (HRSV) is a leading cause of respiratory infections in young children. HRSV cases declined dramatically in the initial stages of the COVID-19 pandemic, followed by a resurgence in 2022/2023. To investigate patterns of viral genetic diversity and evolutionary dynamics during this period, HRSV sequences were analyzed at national and global levels, including newly sequenced samples from pediatric patients at a major Florida medical center in Alachua County. Our Florida strains clustered within multiple clades, with no clear association between specific clades and clinical or epidemiologic characteristics. Phylodynamic analyses suggested post-pandemic changes in HRSV-A and HRSV-B population dynamics, while phylogeographic patterns were compatible with possible viral introductions from European countries. We also detected amino acid diversity in known G-protein epitope regions, indicating a genetic variation in antigenically relevant sites. These findings suggest that post-pandemic HRSV circulation was associated with changes in viral population dynamics and genetic diversity, emphasizing the value of continued genomic surveillance to monitor viral evolution and support future prevention strategies.