Studying interconnections of cytokines and their diagnostic effectiveness when assessing severity grade in COVID-19 patients

The origins and intensity of human immune response to SARS-CoV-2 infection depend on many factors. The anti-infectious immune response includes both cellular and humoral components. The humoral link is mediated by effector-specific (antibodies) and non-specific factors (acute phase proteins, procalcitonin, α- and β-interferons), and regulatory factors, e.g., cytokines (interleukins (IL), γ-interferon (IFNγ)) and mediators (leukotrienes, etc.). In our work, serum levels of cytokines, i.e., IFNγ, IL-2, IL-6, IL-8, IL-10, IL-17A, IL-18 and procalcitonin (PCТ), a nonspecific effector factor of the immune system were compared at varying degrees of COVID-19 severity. Biomaterial samples (blood serum) of 91 patients aged 29-88 years (average age 53.9 years; 15 women, 76 males) were collected between May 2020 and July 2021. We divided patients into groups according to the disease severity, depending on clinical data, oxygen demand, and hospitalization data. COVID-19 patients of “mild degree” (n = 9) were subject to outpatient treatment; the patients of “moderate degree” (n = 38) were hospitalized at the infectious hospital; in the “severe degree” cases (n = 44), the patients were treated at the infectious intensive care unit. The control group of patients (n = 20) was presented by the blood donors without chronic diseases. We have identified the most important markers of the disease severity. Moreover, using ROC analysis, we have calculated the thresholds for differential diagnosis of distinct degrees of COVID-19 severity, by significantly differing criteria, as well as diagnostic efficiency of immune mediator indexes using a developed logistic regression model. We have revealed and statistically confirmed the indices that most significantly influence the COVID-19 severity, i.e., IL-6, IL-8, IL-10, IL-18, PCT, IFNγ. We found a maximum increase in IL-17A and IFNy at a mild degree, and their reduction in the moderate and maximum severe cases of COVID-19. Increase in IL-6, IL-10, PCT levels, and a decrease in IFNγ proved to be the factors of poor prognosis. We have also found some correlations between the immune mediators (IL-8, IL-17A, IL-18, IFNγ) thus allowing a deeper insight into the mechanisms of the disorders, the imbalance of immune response.