Linking molecular evolution and population-level epidemiology of respiratory viruses

Respiratory viruses are a persistent public health burden because of their capacity to repeatedly infect the same host population. This persistence is driven by ongoing virus-host co-evolution, where the virus evolves to escape immunity built through prior infection and vaccination. Seasonal influenza viruses exemplify this dynamic; their continual antigenic evolution permits reinfection across the lifespan and underlies the recurring epidemics observed each year. A central challenge for influenza epidemiology is understanding how molecular-scale processes translate into population-level outcomes including epidemic size and vaccine effectiveness. This thesis addresses these challenges by examining the link between viral molecular evolution and population-level outcomes in detail, and by evaluating how the molecular record captured in viral genomes can best be leveraged to improve public health. It indicates that the relationship between respiratory virus molecular evolution and population-level outcomes is often more complex than assumed. While genomic sequencing remains a powerful public health tool, its limitations, opportunity costs, and resource requirements should be carefully considered. Taken together, this thesis aims to offer a path toward an improved ability to link molecular evolution with population-level epidemiology, with potential benefits for public health interventions and more principled deployment of genomic data in decision-making.