Commuting-driven competition between transmission chains shapes seasonal influenza virus epidemics in the United States

Despite intensive study, much remains unknown about the dynamics of seasonal influenza virus epidemic establishment and spread in the United States (US) each season. By reconstructing transmission lineages from seasonal influenza virus genomes collected in the US from 2014 to 2023, we show that most epidemics consisted of multiple distinct transmission lineages. Spread of these lineages exhibited strong spatiotemporal hierarchies and lineage size was correlated with timing of lineage establishment in the US. Mechanistic epidemic simulations suggest that mobility-driven competition between lineages determined the extent of individual lineages’ geographical spread. Based on phylogeographic analyses and epidemic simulations, lineage-specific movement patterns were dominated by human commuting behavior. These results suggest that given the locations of early-season epidemic sparks, the topology of inter-state human mobility yields repeatable patterns of which influenza viruses will circulate where, but the importance of short-term processes limits predictability of regional and national epidemics.