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

TY - JOUR

T1 - Epidemiological impacts of nonpharmaceutical interventions are modulated by immunity exposure trade offs

AU - Saad-Roy, Chadi M.

AU - Nielsen, Bjarke Frost

AU - Lind, Margaret L.

AU - Wagner, Caroline E.

AU - Traulsen, Arne

AU - Metcalf, C. Jessica E.

AU - Boots, Mike

AU - Cummings, Derek A.T.

AU - Grenfell, Bryan T.

N1 - Publisher Copyright: © The Author(s) 2026.

PY - 2026/12

Y1 - 2026/12

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/105037613170

UR - https://www.scopus.com/pages/publications/105037613170#tab=citedBy

U2 - 10.1038/s43856-026-01492-y

DO - 10.1038/s43856-026-01492-y

M3 - Article

C2 - 42062463

SN - 2730-664X

VL - 6

JO - Communications Medicine

JF - Communications Medicine

IS - 1

M1 - 262

ER -