Characteristics of immunity and disease-induced mortality synergistically complicate epidemiological dynamics

Disease-induced mortality and immunity are two key pathogen-specific drivers of epidemiological dynamics. As highlighted by the COVID-19 pandemic, disease-induced mortality can occur not only during active infection, but also following recovery during a period of immunity or after returning to susceptibility. In parallel, this period of immunity can vary in its average duration and, importantly, in its distribution. While these uncertainties underlie the dynamics of many pathogens, their combined effects remain unknown. To address this gap, we formulate a general framework where individuals return to (potentially partial) susceptibility after one or more recovery classes. We show analytically that disease-induced mortality either during infection or while fully-immune has no qualitative effects if there are two or fewer recovered compartments and individuals return to complete susceptibility. However, with four, five, or six recovered compartments, we numerically find that disease-induced mortality during infection or while immune can be either stabilizing or destabilizing, and that the presence of post-infection mortality while susceptible can enable three switches in stability. Thus, our models reveal that immunity combined with disease-induced mortality can have important epidemiological effects. Our findings therefore illustrate the need to include these effects in pathogen-specific models, and for immuno-epidemiological cohort studies.