Multiplex serology reveals age-specific immunodynamics of respiratory pathogens in the wake of the COVID-19 pandemic.

The rebound of endemic respiratory viruses following the COVID-19 pandemic was marked by atypical transmission dynamics, with children experiencing increased disease burden and out-of-season epidemics as restrictions relaxed. Here we used serology from a newly developed quantitative multiplex assay to assess the post-pandemic immunity debt. We assessed age-specific antibody dynamics across a broad range of respiratory viruses, including influenza, respiratory syncytial virus, seasonal coronaviruses, and SARS-CoV-2 using serology collected in King County, Washington, US, from 2020-2022 (n = 1508). We found that respiratory virus immunodynamics differed between individuals <5 years of age and older individuals, with young children experiencing larger boosts and quicker waning of antibodies across pathogens. We confirmed that these patterns are upheld in a non-pandemic setting by analyzing influenza serology collected in South Africa between 2016-2018 (n = 1028). We incorporated our serological insights into an influenza transmission model calibrated to epidemiological data from King County and show that consideration of age-specific immunodynamics may be important to anticipate the effects of pandemic perturbations.