Patterns of cytokine and chemokine expression in peripheral blood of patients with COVID-19 associated with disease severity

Objectives: Cytokine dysregulation has been proposed as one of the main culprits for severe COVID-19 and poor prognosis. We examined the parallel presence of lymphopoietic, proinflammatory, Th1, Th2, regulatory cytokines, and chemokines in the serum of 47 patients with mild, moderate, and severe COVID-19 and evaluated the association between cytokine concentrations and disease severity. Methods: A multiplex quantitative cytokine analysis ProcartaPlex (TM) immunoassay was applied, using the Luminex(TM) 200X detection system (Invitrogen). Results: The concentrations of twelve cytokines: IL-18, IFN-gamma, TNF-alpha; IL-21; IL-1alpha, IL-1beta, IL-6, IL-22; IL-10, IL-1RA; IL-7 and IFN-alpha were consistently elevated in the studied serum samples. All examined chemokines-Eotaxin, GRO-alpha, IL-8, IP-10, MCP-1, MIP-1alpha, MIP-1beta, SDF-1alpha, and RANTES, were detectable in all studied groups, confirming their importance in mediating the adaptive immune response regardless of disease severity. The serum concentrations of six mediators: IL-1beta, IL-6, IL-18, IL-10, IL-8, and IP-10, showed statistically significant differences among the groups with different disease severity. IL-6, IL-1beta, and IL-10 were more significantly elevated in severe cases while milder symptoms were associated with lower levels of IL-8 and IP-10. Conclusion: Overall, the studied chemokines demonstrated an associated production in acute COVID-19 infection. A strong correlation was observed between the Th1 mediators IL-18 and IL-10 and the proinflammatory IL-6 in the severe COVID-19 group. Our results indicated that severe COVID-19 was characterized by a dysregulated cytokine pattern whereby the Th1 immune response is outweighed by the immunoregulatory response, while inhibitory signals cannot balance the hyperinflammatory response.