Impact of the COVID-19 pandemic on the global burden of pertussis: An analysis of trends and the emergence of an immunity gap

Although the global burden of pertussis has declined steadily over recent decades, the COVID-19 pandemic coincided with a marked disruption of its established epidemic trajectory. We assessed pandemic-associated changes using spatiotemporal trend analysis, health inequality assessment, multivariable regression, and Mendelian randomization. Globally, the age-standardized disability-adjusted life years (DALYs) rate decreased from 378.01 per 100,000 in 1990 to 70.92 in 2021, accelerating steeply after 2019. Despite reductions, burden remained concentrated in low-sociodemographic index (SDI) countries, with widening relative inequalities. Macro-scale multivariable regression stratified by SDI revealed no robust independent association between COVID-19 and pertussis incidence after adjusting for population density. Consistently, Mendelian randomization analyses found no evidence of a causal effect of genetic liability to COVID-19 on pertussis risk. These findings suggest the pandemic-era decline is driven by disruptions to transmission and health services rather than biological cross-protection. We interpret this transient suppression as contributing to an emerging immunity gap - an accumulation of susceptible individuals following reduced natural exposure and interruptions to routine immunization. As social contact patterns normalize, this immunity gap increases the risk of rebound transmission. Strengthening life-course vaccination, including catch-up programmes and prioritization of low-SDI settings, is essential to mitigate post-pandemic resurgence.