We performed a comprehensive analysis of cellular and humoral immune responses to SARS-CoV-2, Epstein-Barr virus (EBV), and human cytomegalovirus in individuals with neuropsychiatric long COVID, a sub...

Background and ObjectivesEpstein-Barr virus (EBV) infection is strongly implicated in multiple sclerosis (MS), yet the mechanisms linking EBV to disease pathogenesis remain unclear. EBV-specific T cel...

Background and ObjectivesEvidence suggests that Epstein-Barr virus (EBV) infection is a necessary, but not sufficient, exposure for developing multiple sclerosis (MS). Although many cases of EBV infec...

Cytomegalovirus (CMV) and Epstein–Barr virus (EBV) are ubiquitous latent herpes viruses, but contemporary population-based seroprevalence data in Japan remain limited, particularly in younger age groups. This study aimed to characterize age- and sex-specific CMV and EBV seroprevalence in a population-based Japanese cohort and to describe combined serostatus patterns across age groups.MethodsWe conducted a cross-sectional seroepidemiological analysis of the Tohoku Medical Megabank Project Birth and Three-Generation (TMM BirThree) cohort. Serum samples collected between 2017 and 2024 were tested for CMV-IgG (age 4–40 years; n = 2247) and EBV viral capsid antigen IgG (age 4–30 years; n = 1647) using commercial ELISA. Seroprevalence was stratified by age and sex. Combined CMV/EBV serostatus patterns were described, and sensitivity analyses assessed temporal consistency and intra-family clustering.ResultsCytomegalovirus seroprevalence increased during childhood and adolescence and plateaued at approximately 70%–80% in early adulthood, whereas EBV seroprevalence rose steadily, exceeding 70% in late adolescence and 90% in the late 20s, with minimal sex differences. Dual seropositivity increased with age, the CMV−/EBV− group declined, and CMV−/EBV+ remained more common than CMV+/EBV− across all age groups. These patterns were consistent in sensitivity analyses.ConclusionsCytomegalovirus and EBV exhibit distinct age-related seroepidemiologic patterns in Japan despite overlapping transmission routes. The early plateau of CMV seroprevalence and near-universal EBV seropositivity by young adulthood indicate divergent infection dynamics with implications for congenital CMV prevention, infectious mononucleosis risk, and ongoing vaccine strategy.