Molecular epidemiology of respiratory syncytial virus infections in Arizona, USA during the 2023-24 and 2024-25 seasons.

Respiratory syncytial virus infection is a common cause of hospitalizations in infants and elderly patients. With the increased availability of vaccines and therapeutic antibodies, surveilling the sequence landscape of viral genomes is important to increase awareness of potentially neutralizing mutations. During the 2023-24 and 2024-25 RSV seasons, we collected unpaired nasopharyngeal swab specimens from patients presenting to Arizona healthcare systems with symptoms of influenza-like illness. Using either tiled am-plicon-based enrichment or a commercial oligo hybrid-enrichment panel and next generation sequencing, we obtained genome sequences for RSV and co-infecting viruses. We performed phylogenetic and genomic analyses to classify RSV genomes and detect mutations in the antigenic sites of the F protein and conserved central domain of the G protein. Phylogenetic analysis showed RSV-A strains belonged to the A.D. 1, A.D.2, A.D.3, and A.D. 5 subclades. RSV-B genomes belonged to the B.D.4.1, B.D.4.1.1, B.D.E.1, B.D.E.5, and B.D.E. 7 clades. We found 9 polymorphic sites located in the antigenic sites of the F protein in our RSV-A genomes and 18 polymorphic sites in our RSV-B genomes over the two-season surveillance period. We identified 7 polymorphic sites in our RSV-A genomes and 8 polymorphic sites in our RSV-B genomes that are in the conserved central domain of the G protein. We also discovered 3 (6.7%) and 27 (15.8%) incidences of viral coinfections in the 2023-24 and 2024-25 seasons, respectively. Viral genomic surveil-lance plays an important role in maintaining the efficacy of vaccine and therapeutic agents. Continued monitoring of circulating variants is an important component of public health.