Immune correlates of post-COVID syndrome at different glucocorticoid levels

Long-term sequelae of COVID-19 include disturbances in the immune and endocrine systems. Of particular interest is the role of cortisol as a key stress response hormone, potentially affecting restoration of immune homeostasis in patients with post-COVID syndrome. Altered regulation of the hypothalamic-pituitary-adrenal axis may form various immune phenotypes that complicate individual adaptation after infection. Our objective was to assess the parameters of immune response in patients with post-COVID syndrome depending on the blood cortisol level, emphasizing the indices on natural killers, T-lymphocytes and platelets. Materials and methods: We have examined 109 patients who had COVID-19 at least 6 months ago. Blood serum samples were collected in the morning time. Serum cortisol levels were measured in order to stratify patients into three groups: with normal, elevated and reduced values. Immune status of the patients was assessed by flow cytometry. The levels of NK cells, T lymphocytes and their subpopulations (helpers, cytotoxic cells) were analyzed both by CD45+ and CD46+ panleukocyte markers, as well as general blood test parameters, including the mean platelet volume. Statistical evaluation was performed by means of nonparametric methods. Results: Patients with low cortisol levels showed a significant reduction in both absolute and relative number of NK cells, as well as a decrease in the average platelet volume. In this group, an increased number of T lymphocytes was also observed. In patients with hypercortisolemia, a decreased level of T cytotoxic cells was recorded. The immune differences clearly correlated with individual cortisol levels. Conclusions: The obtained data demonstrate presence of at least two immune phenotypes in post-COVID patients: (1) a pattern associated with hypercortisolemia and decreased cytotoxic T cells; (2) phenotype with hypocortisolemia, NK cell deficiency and platelet activity. These differences suggest a need for taking the hormonal status into account when assessing and treating post-COVID conditions.

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