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

Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients.
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SARS-CoV-2感染患者外周血淋巴细胞反应和细胞因子谱的纵向特征

DOI:
10.1016/j.ebiom.2020.102763
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发表时间:
2020-05-01
期刊:
影响因子:
11.1
通讯作者:
Zheng, Xin
Zheng, Xin
中科院分区:
医学1区
文献类型:
--
作者:
Liu, Jing;Li, Sumeng;Zheng, Xin

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背景技术背景:新型冠状病毒病患者淋巴细胞亚群及细胞因子谱的动态变化方法:从40例确诊的COVID-19患者中纵向采集外周血样本,通过流式细胞术检测淋巴细胞亚群,通过特异性免疫测定法检测细胞因子谱。在入组的40例COVID-19患者中,13例重度病例显示淋巴细胞计数显著持续下降[0·6(0·6-0·8)],但中性粒细胞计数增加[4·7(3·6-5·8)],而27例轻度病例则为[1·1(0·8-1·4); 2·0(1·5-2·9)]。进一步分析表明,与轻度病例相比,重度病例外周血中T细胞计数显著降低,尤其是CD 8 + T细胞,以及IL-6、IL-10、IL-2和IFN-γ水平升高。在较晚的时间点,幸存的严重COVID-19患者的T细胞计数和细胞因子水平逐渐恢复至与轻度病例相当的水平。此外,嗜中性粒细胞与淋巴细胞比率(NLR)(AUC=0·93)和嗜中性粒细胞与CD 8 + T细胞比率(N8 R)(AUC =0·94)被确定为影响重度COVID-19预后的强有力预后因素。解释:重度COVID-19患者的淋巴细胞减少和促炎细胞因子风暴程度高于轻度病例,且与疾病严重程度相关。N8 R和NLR可作为早期识别重症COVID-19病例的有用预后因子。基金资助:国家自然科学基金、国家科技重大专项、湖北省卫健委、华中科技大学、杜伊斯堡-埃森大学医学院和德国埃森大学医学基金会。
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-gamma 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 of Duisburg-Essen and Stiftung Universitaetsmedizin, Hospital Essen, Germany.