Campus-based genomic surveillance uncovers early emergence of a future dominant A(H3N2) influenza clade

We conducted genomic surveillance during the 2022-2023 northern hemisphere influenza season at a university in the southwestern US to assess how local diversity and evolution compared to national trends. We identified 100 positive samples (19%) from clinical swabs collected at a student health clinic and observed a dominance of subtype A(H3N2) which was consistent nationally for that season. However, we found stark differences when examining H3 clades, including an early dominance of 3C.2a1b.2a.2a.3a.1 variants contrasting from country level data in which 3C.2a1b.2a.2b variants were most abundant. We found known H3 amino acid substitutions in epitope sites and estimated vaccine effectiveness to be 0.13-0.48 which aligns with national estimates for that season. Importantly, 3C.2a1b.2a.2a.3a.1 became the dominant H3 clade nationally in 2023-2024 and 2024-2025, highlighting the potential for localized genomic surveillance in semi-closed, highly dense university settings and its potential for early insight of seasonal influenza diversity.