Abstract
Treatment of severe and critical cases of coronavirus disease 2019 (COVID-19) is still a top priority in public health. Previously, we reported distinct Th1 cytokines related to the pathophysiology of severe COVID-19 condition. In the present study, we investigated the association of Th1 and Th2 cytokine/chemokine endotypes with cell-mediated immunity via multiplex immunophenotyping, single-cell RNA-Seq analysis of peripheral blood mononuclear cells, and analysis of the clinical features of COVID-19 patients. Based on serum cytokine and systemic inflammatory markers, COVID-19 cases were classified into four clusters of increasing (I-IV) severity. Two prominent clusters were of interest and could be used as prognostic reference for a targeted treatment of severe COVID-19 cases. Cluster III reflected severe/critical pathology and was characterized by decreased in CCL17 levels and increase in IL-6, C-reactive protein CXCL9, IL-18, and IL-10 levels. The second cluster (Cluster II) showed mild to moderate pathology and was characterized by predominated CXCL9 and IL-18 levels, levels of IL-6 and CRP were relatively low. Cluster II patients received anti-inflammatory treatment in early-stage, which may have led prevent disease prognosis which is accompanied to IL-6 and CRP induction. In Cluster III, a decrease in the proportion of effector T cells with signs of T cell exhaustion was observed. This study highlights the mechanisms of endotype clustering based on specific inflammatory markers in related the clinical outcome of COVID-19.
Keywords: COVID-19; Th1 inflammation; T cell exhaustion.
【저자키워드】 COVID-19, T cell exhaustion., Th1 inflammation, 【초록키워드】 Treatment, coronavirus disease, public health, pathology, severe COVID-19, Prognosis, IL-6, severity, Th1, Th2, C-reactive protein, CRP, Peripheral blood, Clinical outcome, T cell, pathophysiology, Patient, Clustering, Cluster, Mild, CXCL9, Inflammatory marker, IL-10, prognostic, disease, moderate, clinical feature, mechanism, single-cell, COVID-19 patients, Cell-mediated immunity, association, Analysis, anti-inflammatory treatment, mononuclear cells, Critical case, COVID-19 case, serum cytokine, IL-18, CCL17, systemic inflammatory markers, Prevent, decrease, highlight, Th1 cytokine, proportion, reported, investigated, characterized, reflected, increase in, accompanied, effector T cell, multiplex immunophenotyping, 【제목키워드】 predict, Th1 cytokine, severe complication,