Genomic evolution of influenza during the 2023-2024 season, the johns hopkins health system.

Influenza, a human disease caused by viruses in the Orthomyxoviridae family, is estimated to infect 5% -10 % of adults and 20% -30 % of children annually. Influenza A (IAV) and Influenza B (IBV) viruses accumulate amino acid substitutions (AAS) in the hemagglutinin (HA) and neuraminidase (NA) proteins seasonally. These changes, as well as the dominating viral subtypes, vary depending on geographical location, which may impact disease prevalence and the severity of the season. Genomic surveillance is crucial for capturing circulation patterns and characterizing AAS that may affect disease outcomes, vaccine efficacy, or antiviral drug activities. In this study, whole-genome sequencing of IAV and IBV was attempted on positive remnant clinical samples (587) collected from 580 patients between June 2023 and February 2024 in the Johns Hopkins Health System (JHHS). Full-length HA segments were obtained from 424 (72.2 %) samples. H1N1pdm09 (71.7 %) was the predominant IAV subtype, followed by H3N2 (16.7 %) and IBV-Victoria clade V1A.3a.2 (11.6 %). Within H1N1pdm09 HA sequences, the 6B1A.5a.2a.1 (60.5 %) clade was the most represented. Full-length NA segments were obtained from 421 (71.7 %) samples. Within H1N1pdm09 and IBV, AAS previously proposed to change susceptibility to NA inhibitors were infrequently detected. Phylogeny of HA and NA demonstrated heterogeneous HA and NA H1N1pdm09 and IBV subclades. No significant differences were observed in admission rates or use of supplemental oxygen between different subtypes or clades. Influenza virus genomic surveillance is essential for understanding the seasonal evolution of influenza viruses and their association with disease prevalence and outcomes.