Epidemiological Trends and Clinical Characteristics of Epstein–Barr Virus Infection in Febrile Children in Zhejiang, China: A Retrospective Study

BACKGROUND: This study aimed to investigate the epidemiological trends, age- and sex-related patterns, and clinical and immunological characteristics of Epstein-Barr virus (EBV) infection among febrile children. METHODS: We analyzed EBV DNA data from 9151 febrile children and serological antibody profiles from 6934 cases. A clinical cohort of 377 patients was further evaluated to compare primary infection (N = 246) versus reactivation (N = 131), as well as infectious mononucleosis (IM, N = 134) versus non-IM (N = 112). RESULTS: EBV DNA positivity peaked in autumn (September-October), whereas VCA-IgM levels reached their highest in autumn-winter. Primary infection was most prevalent in children aged 1-9 years, peaking in the 3-6-year age group (58.4%), with higher rates observed in females. Reactivation rates increased with age, reaching 7.8% in children aged ≥ 9 years. Clinically, primary infection is characterized by increased EBV DNA loads, lymphocyte percentages, and atypical lymphocytes and elevated liver enzyme levels. In contrast, reactivation was associated with increased proportions of CD19+ and CD4+ lymphocytes. IM patients had higher lymphocyte percentages, atypical lymphocytes, and liver enzyme abnormalities than non-IM patients did, who had higher neutrophil percentages and hsCRP levels. CONCLUSION: EBV infection in febrile children exhibits distinct seasonal, age-related, and sex-related patterns. Primary infection and IM are clinically distinguished by pronounced liver involvement and lymphocytosis, whereas reactivation and non-IM infections present with different immunological profiles and nonspecific inflammation, providing valuable insights for differential diagnosis and clinical management.