The evolution of post-infection mortality.

Abstract

COVID-19 infections have underlined that there can be substantial impacts on health after recovery, including elevated mortality. While such post-infection mortality (PIM) is clearly widespread, we do not yet have any understanding of its evolutionary dynamics. To address this gap, we use an eco-evolutionary model to determine conditions where PIM is evolutionarily favoured. Importantly, from a pathogen perspective, there are two potential 'resources': never-infected susceptibles and previously infected susceptibles (provided some reinfection is possible), and PIM only occurs in the latter. A key insight is that unlike classic virulence (i.e. during-infection mortality, DIM) PIM is neutral and not selected against in the absence of other trade-offs. However, PIM modulates characteristics of endemicity, and may also vary with other pathogen-specific components. If PIM is only correlated with transmission, recovery or DIM, it simply acts to modulate their impacts on the evolutionary outcome. On the other hand, if PIM trades off with the relative susceptibility to reinfection, there are important evolutionary implications that contrast with DIM. We find settings where a susceptibility-mortality trade-off (i.e. an increase in mortality leads to higher relative susceptibility to reinfection) can select against DIM but favour PIM. This provides a potential explanation for the ubiquity of PIM. Overall, our work illustrates that PIM can readily evolve in certain settings and highlights the importance of considering different sources of mortality.