Abstract

Coronavirus disease 2019 (COVID-19) is an acute respiratory disease of variable severity, and treatment of severe and critical cases is of major medical importance. Cytokine release is associated with disease severity, and we reported that T1 cytokines are related to the pathophysiology of severe disease. However, the relationship with cell-mediated immunity, which drives cytokine production, was not investigated. In this study we measured serum cytokine levels and peripheral blood lymphocyte subsets in 108 patients with COVID-19, and evaluated the relationship between cytokine-defined endotypes and cell-mediated immunity as well as disease severity. Serum IL-6, CRP, CXCL9, IL-18, and VEGF levels were significantly increased, and CCL17 decreased, in severe and critical patients compared with mild and moderate patients. The patients were classified into 4 clusters based on levels of these inflammatory markers. We confirmed a distinct inflammatory endotype of COVID-19 that was related to severe symptoms. In this endotype, levels of T1-inflammatory markers were increased in addition to IL-6 and CRP, and despite high cytokine levels, there were suggestions of inefficient immune response due to exhaustion of effector T cells. In addition, a predominant T1 inflammatory endotype was identified. This endotype may be a result of anti-inflammatory treatment in the early stage of disease.
A patent application has been filed.