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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。

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

机构信息

Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China.

Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.

出版信息

EBioMedicine. 2020 May;55:102763. doi: 10.1016/j.ebiom.2020.102763. Epub 2020 Apr 18.

DOI:10.1016/j.ebiom.2020.102763
PMID:32361250
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7165294/
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 of Duisburg-Essen and Stiftung Universitaetsmedizin, Hospital Essen, Germany.

摘要

背景

新型冠状病毒病(COVID-19)患者淋巴细胞亚群和细胞因子谱的动态变化及其与疾病严重程度的关系尚不清楚。

方法

通过流式细胞术对 40 例确诊 COVID-19 患者的外周血样本进行淋巴细胞亚群检测,采用特异性免疫分析方法检测细胞因子谱。

结果

在纳入的 40 例 COVID-19 患者中,13 例重症患者的淋巴细胞计数明显且持续下降[0.6(0.6-0.8)],而中性粒细胞计数升高[4.7(3.6-5.8)],与 27 例轻症患者相比[1.1(0.8-1.4);2.0(1.5-2.9)]。进一步分析表明,与轻症患者相比,重症患者外周血 T 细胞,特别是 CD8 T 细胞计数明显减少,IL-6、IL-10、IL-2 和 IFN-γ 水平升高。重症 COVID-19 患者存活后,T 细胞计数和细胞因子水平逐渐恢复到与轻症患者相当的水平。此外,中性粒细胞与淋巴细胞比值(NLR)(AUC=0.93)和中性粒细胞与 CD8 T 细胞比值(N8R)(AUC=0.94)被确定为影响重症 COVID-19 预后的有力预后因素。

结论

与轻症患者相比,重症 COVID-19 患者的淋巴细胞减少程度和促炎细胞因子风暴更高,与疾病严重程度相关。N8R 和 NLR 可能是早期识别重症 COVID-19 病例的有用预后因素。

资助

国家自然科学基金、国家重大科技专项、湖北省卫生健康委员会、华中科技大学、德国埃森杜伊斯堡-埃森大学和埃森大学医学基金会、埃森医院。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99e5/7195532/cc4f9a57c210/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99e5/7195532/fdfe1d17bdd8/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99e5/7195532/51f96d688800/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99e5/7195532/75c71bdc971a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99e5/7195532/cc4f9a57c210/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99e5/7195532/fdfe1d17bdd8/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99e5/7195532/51f96d688800/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99e5/7195532/75c71bdc971a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/99e5/7195532/cc4f9a57c210/gr4.jpg

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