Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients

Liu, Jing; Li, Sumeng; Liu, Jia; Liang, Boyun; Wang, Xiaobei; Wang, Hua; Li, Wei; Tong, Qiaoxia; Yi, Jianhua; Zhao, Lei; Xiong, Lijuan; Guo, Chunxia; Tian, Jin; Luo, Jinzhuo; Yao, Jinghong; Pang, Ran; Shen, Hui; Peng, Cheng; Liu, Ting; Zhang, Qian; Wu, Jun; Xu, Ling; Lu, Sihong; Wang, Baoju; Weng, Zhihong; Han, Chunrong; Zhu, Huabing; Zhou, Ruxia; Zhou, Helong; Chen, Xiliu; Ye, Pian; Zhu, Bin; Wang, Lu; Zhou, Wenqing; He, Shengsong; He, Yongwen; Jie, Shenghua; Wei, Ping; Zhang, Jianao; Lu, Yinping; Wang, Weixian; Zhang, Li; Li, Ling; Zhou, Fengqin; Wang, Jun; Dittmer, Ulf; Lu, Mengji; Hu, Yu; Yang, Dongliang; Zheng, Xin

Abstract Background The dynamic changes of lymphocyte subsets and cytokines profiles of patients with novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. Methods Peripheral blood samples were longitudinally collected from 40 confirmed COVID-19 patients and examined for lymphocyte subsets by flow cytometry and cytokine profiles by specific immunoassays. Findings Of the 40 COVID-19 patients enrolled, 13 severe cases showed significant and sustained decreases in lymphocyte counts [0•6 (0•6-0•8)] but increases in neutrophil counts [4•7 (3•6-5•8)] than 27 mild cases [1.1 (0•8-1•4); 2•0 (1•5-2•9)]. Further analysis demonstrated significant decreases in the counts of T cells, especially CD8+ T cells, as well as increases in IL-6, IL-10, IL-2 and IFN-γ levels in the peripheral blood in the severe cases compared to those in the mild cases. T cell counts and cytokine levels in severe COVID-19 patients who survived the disease gradually recovered at later time points to levels that were comparable to those of the mild cases. Moreover, the neutrophil-to-lymphocyte ratio (NLR) (AUC=0•93) and neutrophil-to-CD8+ T cell ratio (N8R) (AUC =0•94) were identified as powerful prognostic factors affecting the prognosis for severe COVID-19. Interpretation The degree of lymphopenia and a proinflammatory cytokine storm is higher in severe COVID-19 patients than in mild cases, and is associated with the disease severity. N8R and NLR may serve as a useful prognostic factor for early identification of severe COVID-19 cases. Funding The National Natural Science Foundation of China, the National Science and Technology Major Project, the Health Commission of Hubei Province, Huazhong University of Science and Technology, and the Medical Faculty of the University Hospital Essen, Germany.