Impact of infection timing before vaccination on the effectiveness of COVID-19 mRNA vaccine in healthcare workers.

UNLABELLED: The coronavirus disease 2019 (COVID-19) outbreak has prompted various public health interventions, including widespread vaccination campaigns. While vaccine effectiveness is widely studied, limited evidence exists on how it is influenced by the timing of previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This study aimed to evaluate the impact of prior infection timing on the effectiveness of subsequent COVID-19 mRNA vaccination in preventing SARS-CoV-2 infection. We conducted a cohort study of healthcare workers during the 10th wave of COVID-19 in Japan (January-July 2024) to evaluate whether prior infection history influences subsequent infection rates. Participants were categorized based on sex, age, vaccination status, and prior infection history, which was classified as infected within the past year (January to December 2023), infected more than a year ago (before December 2022), or never infected. Infection rates were compared among these groups. Vaccination in 2023 was associated with a significant reduction in infection rates across all groups, with a notable reduction in those infected before 2022 (risk ratio: 0.36, 95% CI: 0.19-0.66). The strongest protective effect was observed among individuals whose last infection occurred more than one year prior to vaccination. In contrast, vaccination showed a less substantial effect on individuals who had been infected within one year prior to receiving the vaccine. These findings suggest that COVID-19 vaccination remains a critical strategy for preventing infection, particularly among individuals with prior infection occurring more than 1 year earlier.

IMPORTANCE: Understanding how prior infection timing affects the effectiveness of booster vaccination is essential for optimizing COVID-19 immunization strategies. While mRNA vaccines have demonstrated strong protection, their impact may vary depending on the interval between natural infection and vaccination. This study evaluates vaccine effectiveness among healthcare workers stratified by infection history, revealing that individuals whose last infection occurred more than one year before vaccination experienced the greatest benefit. In contrast, those with recent infections showed a less pronounced response. These findings suggest that immune memory and timing of antigen exposure play a critical role in booster performance. By identifying subgroups with differential vaccine responsiveness, this research provides actionable insights for tailoring booster recommendations, particularly during periods of high transmission risk.