Genomic and Antigenic Evolution of Influenza A(H3N2) After the COVID-19 Era: A Scoping Review with Focus on J and K Subclades and Implications for Vaccine Effectiveness

Post-COVID-19, influenza A(H3N2) has re-emerged with accelerated genetic diversification. The rise in antigenically drifted subclades raises concerns regarding immune escape and vaccine mismatch. To synthesize the available evidence on the post-pandemic evolution of influenza A(H3N2), with particular attention to emerging subclades and their potential public health implications, a scoping review (PRISMA-ScR) was conducted across six databases in January 2026, including studies on genomic surveillance, antigenic characterization, and vaccine effectiveness (VE). Twenty studies were included. While clade 2a.3a.1 (J lineage) predominated, reports highlighted the rapid emergence of the antigenically distinct K subclade (formerly J.2.4.1). Genetic and laboratory assays (HI/neutralization) confirmed immune escape and reduced vaccine match. Observational estimates indicated diminished VE against drifted strains, though no consistent increase in clinical severity was observed. Post-pandemic A(H3N2) is defined by rapid drift and diversification. Emerging variants like the K subclade challenge vaccine selection and seasonal preparedness. Integrated surveillance remains vital for timely vaccine updates and mitigating public health impact.