Pandemic-Driven Shifts in RSV Diversity, Evolution, and Global Spread

The COVID-19 pandemic dramatically disrupted the seasonal circulation of RSV, with subsequent heterogeneous global resurgence. We aimed to characterize how pandemic-era disruptions restructured global RSV transmission dynamics, evolutionary patterns, and drivers of reemergence. We show that RSV-A and RSV-B genetic diversity underwent profound pandemic-associated suppression followed by heterogeneous resurgence. The post-pandemic period was characterized by pronounced changes in diversity, with the emergence of novel RSV-A genotypes (A.D.3 and A.D.5.2) and the expansion of the RSV-B, B.D.E.1 genotype. The recovery of RSV-B deviated strongly from neutral expectations and positive selection was detected at 20 sites in the G glycoprotein, F fusion protein, and M2-2 regulatory protein. Phylogeographic reconstruction revealed a sharp decline in international viral spread during the pandemic, followed by increasing persistence. Europe consistently served as the predominant global source, followed by Western Pacific and North America. Air-travel volume was the strongest predictor of dissemination (log coefficient >0.68 for both subtypes). Post-pandemic RSV resurgence represented fundamental epidemiological restructuring shaped by a population bottleneck, positive selection and major impact of air-travel. These findings underscore the need for robust genomic surveillance to track the global circulation of lineages, and to monitor effectiveness of pharmaceutical interventions given the emergence of new genotypes.