Variability of changes in proand antiinflammatory cytokines due to IFNα and IFNγ deficiency in patients with post-covid syndrome associated with activation of chronic herpes viral infections

Abstract

Post-COVID syndrome (PCS) is characterized by long-term complications and conditions accompanied by neuroimmunoinflammation, and includes chronic fatigue syndrome (CFS) and cognitive disorders (CD), which are often associated with activation of chronic herpesvirus infections (HVI). Timely detection of symptoms and immunodiagnosis of PCS are a priority and are of undoubted interest. Objective: to clarify the levels of serum proand anti-inflammatory cytokines, alpha and gamma interferons in patients with post-COVID syndrome associated with confirmed activation of chronic herpesvirus infections. Patients (n = 60) aged from 18 to 65 years with complaints of manifestations of PCS associated with HVI were studied — the study group (SG). A survey was conducted using a modified scale-questionnaire to assess the severity of PCS symptoms in points from 0 to 4, real-time PCR of HVI (EBV, HSV1/2, VCH6, VCH8, CMV) in saliva and scrapings from the tonsils, determination of the level of IFNα and IFNγ, pro- (TNFα, IL-18, IL-1β, IL-6, IL-17A, IL-8) and anti-inflammatory (IL-4 and IL-10) cytokines in blood serum. Comparison group (CG) — 60 apparently healthy individuals. SG patients with mixed HVI with EBV dominance noted the most pronounced and persistent clinical manifestations of PCS, among which the leading place was occupied by longterm sensations of CFS and CD. A persistent multisystem inflammatory response was identified, confirmed by elevated levels of IL-6 and IL-17A, which caused severe PCS. In post-COVID period, hyperproduction of IL-1β was detected, which was accompanied by clinical manifestations of persistent neuroimmunoinflammation. At the same time, the identified deficiency of IFNα, IFNγ and dysregulatory disorders in the antiviral defense of the immune system in patients with PCS contributed to the activation of HVI. Data on the imbalance of proand anti-inflammatory cytokines in the SG were obtained, which confirms the presence of a persistent multisystem inflammatory reaction with dominance of persistent neuroimmunoinflammation, which causes severe PCS. An imbalance of the cytokine system with IFNα and IFNγ deficiency, associated with the activation of chronic HVI with EBV dominance in the post-COVID period, contributes to the development of neuroimmunoinflammation, which is accompanied by the leading clinical signs of PCS: CFS and CD.