Reduction and Functional Exhaustion of T Cells in Patients with Coronavirus Disease 2019 (COVID-19)

作者：Bo Diao, Chenhui Wang, Yingjun Tan, Xiewan Chen, Ying Liu, Lifen Ning, Li Chen, Min Li, Yueping Liu, Gang Wang, Zilin Yuan, Zeqing Feng, Yuzhang Wu, Yongwen Chen · 发表于：medRxiv · 年份：2020 · DOI：10.1101/2020.02.18.20024364 · 被引用次数：365 · 研究领域：COVID-19 Clinical Research Studies、SARS-CoV-2 and COVID-19 Research、Long-Term Effects of COVID-19

Summary BACKGROUND The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health, which has been declared a public health emergency of international concern (PHEIC) by the WHO. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. METHODS We retrospectively reviewed the counts of total T cells, CD4 + , CD8 + T cell subsets, and serum cytokine concentration from inpatient data of 522 patients with laboratory-confirmed COVID-19, admitted into two hospitals in Wuhan from December 2019 to January 2020, and 40 healthy controls, who came to the hospitals for routine physical examination. In addition, the expression of T cell exhaustion markers PD-1 and Tim-3 were measured by flow cytometry in the peripheral blood of 14 COVID-19 cases. RESULTS The number of total T cells, CD4 + and CD8 + T cells were dramatically reduced in COVID-19 patients, especially among elderly patients (⩾60 years of age) and in patients requiring Intensive Care Unit (ICU) care. Counts of total T cells, CD8 + T cells or CD4 + T cells lower than 800/μL, 300/μL, or 400/μL, respectively, are negatively correlated with patient survival. Statistical analysis demonstrated that T cell numbers are negatively correlated to serum IL-6, IL-10 and TNF-α concentration, with patients in decline period showing reduced IL-6, IL-10 and TNF-α concent...