Immunity features and reactivation of herpesvirus infections in patients with post-COVID-19 syndrome and cytomegalovirus reactivation

Abstract

This study concerns an important medical issue, i.e., the impact of cytomegalovirus (CMV) reactivation on adaptive immunity and overall activation of herpesviruses in patients affected with post-COVID-19 syndrome. CMV is characterized by its ability for lifelong persistence and reactivation in immunocompromised persons, thus making its study critically important, due to consequences of the novel coronavirus infection. The objective of our work was to establish a relationship between the presence of active CMV infection, and development of immune system disorders, as well as its synergism with other herpesviruses. During the study, one hundred and sixty-two patients with symptoms of post-COVID-19 syndrome were examined and divided into two groups based on the presence of specific IgM antibodies against CMV. The research methods included ELISA, PCR technique, and multi-parameter immunophenotyping of peripheral blood lymphocytes using flow cytometry, with statistical analysis performed by the Mann–Whitney U test. The results of the study have shown that the persons with proven CMV reactivation exhibit significantly higher activity of other members of the herpesvirus family, e.g., herpes simplex virus I and II, Epstein–Barr virus, and human herpesvirus type 6. The immunological profile of these patients was characterized by pronounced leukopenia, decreased relative number of T helper cells, deficiency of B cells (type 2), and non-memory B cells, along with compensatory increases in total IgA and IgM levels Particular attention is drawn to the revealed evidence of a cell differentiation block in acute phase of combined infections, manifesting with increased number of naive T cells, along with deficiency of functional effector components. In the case of a chronic infection course, an accumulation of specific markers of immune aging was noted, specifically, T effector memory cells with terminal differentiation markers of. In conclusion, the authors state that CMV reactivation in post-COVID-19 syndrome may serve as a marker and trigger for profound restructuring of adaptive immunity, contributing to systemic activation of herpesvirus infections. These findings confirm the hypothesis that post-COVID changes create a unique environment for latent viruses allowing to escape the immune control, thus requiring special attention upon diagnostics and treatment of such patients.