This article presents an analysis of the clinical variability and diagnostic challenges associated with Epstein–Barr virus (EBV) infection in pediatric and adult populations. The study is based on an interdisciplinary approach, integrating data from virology, clinical immunology, and infectious disease pathology. The analysis focuses on age-specific clinical manifestations of EBV infection, differences in immunological markers and viral load, and the complexity of laboratory data interpretation in cases of chronic active EBV infection (CAEBV). Seropidemiological data from pediatric and adult cohorts are reviewed, including studies conducted in India, China, Japan, and Taiwan. Key clinical phenotypes are systematized across age groups, with detailed descriptions of typical manifestations of mononucleosis, latent and reactivated forms. Pathogenetic associations between EBV and autoimmune conditions (notably multiple sclerosis and inflammatory bowel disease) as well as lymphoproliferative disorders are explored. Particular attention is paid to diagnostic algorithms ranging from serological panels (VCA IgM/IgG, EBNA) to molecular and cytometric methods (PCR, EBER hybridization, T/NK-cell phenotyping). The analysis reveals a high level of diagnostic uncertainty, especially in atypical pediatric cases and chronic adult forms. Proposed approaches to diagnostic standardization take into account viral persistence, immune background, and geoepidemiological factors. The article includes three comparative tables illustrating age-related differences in clinical and laboratory features, symptom spectrum, and immunological markers of CAEBV. This work will be of value to clinicians, infectious disease specialists, immunologists, and researchers studying post-viral complications and systemic pathology associated with EBV persistence.

Epstein–Barr virus, mononucleosis, persistence, serology, immunopathology, autoimmunity, lymphoproliferation, diagnostics, demyelination, cytometry, inflammation, chronic infection.

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