Increased Pro Th1 And Th17 Transcriptional Activity In Patients With Severe COVID-19

Abstract

Background : COVID-19 is known to disrupt immune response and induce hyperinflammation that could potentially induce fatal outcome of the disease. Until now, it is known that interplay among cytokines is rather important for clinical presentation and outcome of COVID-19. The aim of this study was to determine transcriptional activity and functional phenotype of T cells and the relationship between pro- and anti-inflammatory cytokines and clinical parameters of COVID-19 severity. Methods : All recruited patients met criteria for COVID-19 are were divided in four groups according to disease severity. Serum levels of IL-12, IFN-γ, IL-17 and IL-23 were measured, and flow cytometry analysis of T cells from peripheral blood was performed. Results : Significant elevation of IL-12, IFN-γ, IL-17 and IL-23 in stage IV of the disease has been revealed. Further, strong intercorrelation between IL-12, IFN-γ, IL-17 and IL-23 was also found in stage IV of the disease, marking augmented Th1 and Th17 response. Analyses of T cells subsets indicate a noticeable phenotype change. CD4 + , but not CD8 + T cells expressed increased transcriptional activity through increased expression of Tbet and RORγT, accompanied with increased percentage of IFN-γ and IL-17 producing T cells. Conclusion : Our results pose a novel hypothesis of the underlying mechanism behind deteriorating immune response in severe cases of COVID-19.

Tuberculosis and COVID-19 Dually Affect Human Th17 Cell Immune Response

“…Lymphopenia has been described in many patients with COVID-19, primarily characterized by lowered CD4+ and CD8+ T-cell counts also observed in several coronavirus infections [ 28 ]. SARS-CoV-2-specific CD4+ T cells express IFN-γ, TNF-ά, and IL-2, evidencing about developing Th1-type cell response [ 73 ]. An important role of CD4+ T-cells has been shown in murine models, wherein reduced T-lymphocyte count promoted the emergence of more prominent pulmonary inflammation.…”

Innate immunity and early liver inflammation

“…a-PD-1 therapy has shown to invigorate bacteria clearance, but it also suggests that KCs may have impaired tolerogenic function to self-antigens reactive T cells. NKT cells also responded to a-PD-1 therapy and exert increased anti-tumor functions by secretion of IFN-g secretion of inflammatory cytokines (205).…”