Сhronic Epstein–Barr virus infection as a modulator of post-COVID syndrome severity: implications of complement cascade dysregulation and neutrophil immune dysfunction

COVID-19 infection caused by SARS-CoV-2 virus remains a significant concern not only due to acute manifestations but also because of long-term sequelae, including post-COVID syndrome (PCS). Immunological studies demonstrate a pronounced effect of Epstein–Barr virus (EBV) infection on PCS progression. Patients exhibit both quantitative alterations in immune cell populations and qualitative impairments in their functional activity, particularly affecting T cell immunity and innate immune responses, which contribute to the syndrome persistence. EBV (human herpesvirus 4), one of the most prevalent chronic infections, establishing lifelong latency. The interplay between EBV and host immunity is complex: while the immune system generates virus-specific antibodies to control infection, EBV employs immune evasion strategies, impairing host defenses and facilitating viral persistence. Key findings reveal that chronic EBV infection significantly disrupts the immunopathogenesis of PCS, notably via complement suppression (reduced C3a, C5a) and impaired neutrophil phagocytosis, correlating with clinical severity. This synergy between PCS and EBV leads to innate immune dysregulation, chronic inflammation, and interferon response dysfunction. These results underscore the importance of EBV status assessment in PCS patients. Complement and phagocytosis markers may serve as prognostic indexes, guiding personalized therapeutic strategies, including immunomodulation and complement inhibition. Further research is needed to evaluate long-term risks, including autoimmune complications, and to develop targeted interventions.