Eco-Evolutionary Constraints for the Endemicity of Rapidly Evolving Viruses

Antigenic escape constitutes the main mechanism allowing rapidly evolving viruses to achieve endemicity. Beyond granting immune escape, empirical evidence also suggests that mutations of viruses might increase their interhost infectiousness. While both mechanisms are well-studied individually, their combined effects on viral endemicity remain to be explored. Here we propose a minimal eco-evolutionary framework to simulate epidemic outbreaks generated by pathogens evolving both their infectiousness and immune escape. Our results reveal that the main driver of viral evolution shifts over time: from intrinsic selection for infectiousness at early stages of the outbreak to antigenic diversification in the transition to the endemic phase. We find that the evolution in both traits during the first epidemic wave plays a critical role in determining long-term viral persistence. Evolution in infectiousness enhances the endemicity of viruses, especially in viruses with lower baseline infectiousness due to the longer duration of their first epidemic wave. Likewise, control policies flattening epidemic curves might increase viral endemicity as a result of the greater antigenic diversity generated in the prolonged epidemic waves. Our results thus prove that the long-term behavior of epidemic trajectories hinges on the complex interplay between both evolutionary pathways and the underlying contagion dynamics.