Epidemiological impacts of nonpharmaceutical interventions are modulated by immunity exposure trade offs

BACKGROUND: The COVID-19 pandemic has illustrated how nonpharmaceutical interventions (NPIs), such as mask-wearing, social distancing, and purifying air, can successfully mitigate transmission and reduce infections in the short term. However, the longer-term implications of these interventions on infection levels are less clear. In tandem, recent observational evidence suggests that the relative susceptibility of partially immune individuals to infection may be dose-dependent, i.e., higher exposures are more likely to result in (re)infection in individuals with prior immunity from infection or vaccination. METHODS: To examine this question, we use mechanistic immuno-epidemiological models to determine the equilibrium infection levels with NPI-induced reductions in transmission in the presence of this dose-dependency. RESULTS: We find that NPIs can successfully decrease the number of infections at endemicity, even in high transmission scenarios. We also show that this effect is heightened by vaccination, especially if a durable, broadly-protective (i.e., broad antigen specificity) vaccine is deployed. Finally, we find that NPI-induced declines in infection levels are strongly magnified if the characteristics of subsequent infections, such as transmissibility or duration, are also dose-dependent. CONCLUSIONS: Overall, our results suggest that the long-term usage of NPIs could successfully reduce infections especially where immunity-exposure trade-offs apply due to dose-dependency, and illustrate the urgent need to characterize the underlying relationships between exposure and host immune responses.