The inhibition of IL-2/IL-2R gives rise to CD8+ T cell and lymphocyte decrease through JAK1-STAT5 in critical patients with COVID-19 pneumonia

Background: Although most patients with COVID-19 pneumonia have a good prognosis, some patients develop to severe or critical cases, and the mortality of critical cases was up to 61.5%. However, specific information and molecular mechanism about critical patients with COVID-19 was poorly understood. Methods: A total of 54 patients were enrolled and divided into three groups, among which 34 were common type, 14 were severe type, and 6 were critical type. The constitution of peripheral blood mononuclear cells (PBMC) in patients was analyzed by CyTOF. The profile of cytokines was performed in plasma of patients using Luminex. The IL-2 signaling pathway was investigated in the PBMC of patients by qRT-PCR. Results: The lymphocytes count and percentage were significantly decreased in critical patients compared to common and severe patients with COVID-19 pneumonia. CD8+T cells were remarkably decreased in critical patients compared to common, severe patients and normal controls, which suggested the decrease of lymphocytes may be attributed to the reduction of T cells in critical patients. The expression of IL-2R, JAK1, and STAT5 decreased in immune cells of common, severe, and critical patients, but IL-2 level was elevated in severe patients and decreased in critical patients with COVID-19 pneumonia. Conclusion: The decrease of CD8+T cells in critical patients with COVID-19 pneumonia may be related to the IL-2 signaling pathway. The inhibition of IL-2/IL-2R gives rise to CD8+T cell and lymphocyte decrease through JAK1-STAT5 in critical patients with COVID-19 pneumonia. Funding Statement: This study was financially supported by COVID-19 Key Technology Research and Development Funding of Beijing Hospital Authority; The National Natural Science Foundation of China (81672026); National Science and Technology Major Project of China (2018ZX10302205-005). Declaration of Interests: The authors confirm that there are no conflicts of interest. Ethics Approval Statement: The study was approved by the Ethics Committee of Beijing Youan Hospital, Capital Medical University, China.