Cytokine profile in children with mono- and mixed COVID-19 and herpesvirus infections

Study aim is to assess the clinical significance of changes in the cytokine profile in children with mononucleosis-like syndrome associated with SARS-CoV-2 and herpesvirus infection.

Materials and methods. The study included 100 children hospitalized with a diagnosis of COVID-19, herpesvirus infection, with clinical manifestations of mononucleosis-like syndrome. Group 1 consisted of 15 patients with COVID-19 combined with herpesvirus infection (SI, n=15); group 2 — 27 children with COVID-19 without herpesvirus infection; group 3 — 58 patients with active herpesvirus infection. The levels of cytokines (IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-α, IFN-γ) in the blood were investigated, and the relationship between the obtained results and clinical-laboratory parameters was assessed.

Results. The levels of IL-4 (16.4 pg/mL) and IL-10 (32.9 pg/mL) were the highest in the CoI group. Significant elevation of major proinflammatory cytokines (IL-1, IL-6, IL-8, TNF-α) was not observed, excepting IL-2. The level of IL-2 was approximately twice the normal value in the co-infection group (23.3 pg/mL) and significantly higher in the COVID-19 monoinfection group (52 pg/ mL) and in monovariant herpesvirus infections (57.4 pg/mL). Correlation analysis revealed associations between changes in proinflammatory cytokine levels and the duration of hospitalization, fever (IL-2, IL-8), dyspnea (IL-1, IL-2, IL-6, IL-8, TNF-α), and lymphadenopathy (IL-1, IL-6, TNF-α); similar effects were recorded for IFN-γ.

Discussion and conclusion. The cytokine profile in children with combined SARS-CoV-2 and herpesvirus infection is characterized by a moderate increase in IL-2 levels, which indirectly indicates suppression of proliferation and differentiation of CD8⁺ lymphocytes — key factors in the immunological surveillance of latent herpesviruses. Increased production of IL-4 and IL-10 in CoI demonstrates a shift in the immune response towards a Th2 profile. The obtained data suggest that active SARS-CoV-2 infection creates conditions for the reactivation of latent herpesviruses.

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