Heterogeneity in susceptibility dictates the order of epidemic models

The fundamental models of epidemiology describe the progression of an infectious disease through a population using compartmentalized differential equations, but typically do not incorporate population-level heterogeneity in infection susceptibility. Here we combine a generalized analytical framework of contagion with computational models of epidemic dynamics to show that variation strongly influences the rate of infection, while the infection process simultaneously sculpts the susceptibility distribution. These joint dynamics influence the force of infection and are, in turn, influenced by the shape of the initial variability. We find that certain susceptibility distributions (the exponential and the gamma) are unchanged through the course of the outbreak, and lead naturally to power-law behavior in the force of infection; other distributions are often sculpted towards these "eigen-distributions" through the process of contagion. The power-law behavior fundamentally alters predictions of the long-term infection rate, and suggests that first-order epidemic models that are parameterized in the exponential-like phase may systematically and significantly over-estimate the final severity of the outbreak. In summary, our study suggests the need to examine the shape of susceptibility in natural populations as part of efforts to improve prediction models and to prioritize interventions that leverage heterogeneity to mitigate against spread.