Epstein-Barr virus serological profiles and atypical patterns in a large tertiary-care cohort: a retrospective study of 11,503 patients.

Abstract

Epstein-Barr virus (EBV) infection is highly prevalent worldwide, and its seroepidemiology varies according to age and sociodemographic factors. Recent observations suggest potential shifts in exposure dynamics following the COVID-19 pandemic and ongoing challenges in interpreting atypical antibody profiles. This retrospective study evaluated EBV serological patterns in 11,503 patients tested VCA IgM, VCA IgG, EA IgG, and EBNA IgG between January 2023 and August 2025 at a tertiary-care hospital. Patterns were classified as seronegative, primary infection, past infection, reactivation pattern, or atypical. Age- and sex-related distributions were analyzed using logistic regression. Past infection was the most frequent profile (64.0%), followed by seronegativity (19.8%) and atypical patterns (14.3%). VCA IgG seropositivity reached 53.2% in the 5-9 age group and increased with age. Age was strongly associated with EBV seropositivity, and female sex independently increased the odds of VCA IgG positivity. Atypical serological patterns were more common in younger individuals and showed an inverse association with age, while sex had no independent effect. Isolated VCA IgG positivity was the most common atypical pattern. These findings provide updated data on EBV serological patterns in a large tertiary-care cohort during the post-pandemic period. The observed age-specific seropositivity rates may suggest a trend toward later EBV exposure; however, the absence of a direct pre-pandemic comparator requires cautious interpretation. Accurate interpretation of atypical EBV serological profiles remains important in clinical practice and should consider patient age, timing of antibody responses, and analytical characteristics of the assay.