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

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 e...

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Main Authors: Jing Liu, Sumeng Li, Jia Liu, Boyun Liang, Xiaobei Wang, Hua Wang, Wei Li, Qiaoxia Tong, Jianhua Yi, Lei Zhao, Lijuan Xiong, Chunxia Guo, Jin Tian, Jinzhuo Luo, Jinghong Yao, Ran Pang, Hui Shen, Cheng Peng, Ting Liu, Qian Zhang, Jun Wu, Ling Xu, Sihong Lu, Baoju Wang, Zhihong Weng, Chunrong Han, Huabing Zhu, Ruxia Zhou, Helong Zhou, Xiliu Chen, Pian Ye, Bin Zhu, Lu Wang, Wenqing Zhou, Shengsong He, Yongwen He, Shenghua Jie, Ping Wei, Jianao Zhang, Yinping Lu, Weixian Wang, Li Zhang, Ling Li, Fengqin Zhou, Jun Wang, Ulf Dittmer, Mengji Lu, Yu Hu, Dongliang Yang, Xin Zheng
Format: Article
Language:English
Published: Elsevier 2020-05-01
Series:EBioMedicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2352396420301389
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language English
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author Jing Liu
Sumeng Li
Jia Liu
Boyun Liang
Xiaobei Wang
Hua Wang
Wei Li
Qiaoxia Tong
Jianhua Yi
Lei Zhao
Lijuan Xiong
Chunxia Guo
Jin Tian
Jinzhuo Luo
Jinghong Yao
Ran Pang
Hui Shen
Cheng Peng
Ting Liu
Qian Zhang
Jun Wu
Ling Xu
Sihong Lu
Baoju Wang
Zhihong Weng
Chunrong Han
Huabing Zhu
Ruxia Zhou
Helong Zhou
Xiliu Chen
Pian Ye
Bin Zhu
Lu Wang
Wenqing Zhou
Shengsong He
Yongwen He
Shenghua Jie
Ping Wei
Jianao Zhang
Yinping Lu
Weixian Wang
Li Zhang
Ling Li
Fengqin Zhou
Jun Wang
Ulf Dittmer
Mengji Lu
Yu Hu
Dongliang Yang
Xin Zheng
spellingShingle Jing Liu
Sumeng Li
Jia Liu
Boyun Liang
Xiaobei Wang
Hua Wang
Wei Li
Qiaoxia Tong
Jianhua Yi
Lei Zhao
Lijuan Xiong
Chunxia Guo
Jin Tian
Jinzhuo Luo
Jinghong Yao
Ran Pang
Hui Shen
Cheng Peng
Ting Liu
Qian Zhang
Jun Wu
Ling Xu
Sihong Lu
Baoju Wang
Zhihong Weng
Chunrong Han
Huabing Zhu
Ruxia Zhou
Helong Zhou
Xiliu Chen
Pian Ye
Bin Zhu
Lu Wang
Wenqing Zhou
Shengsong He
Yongwen He
Shenghua Jie
Ping Wei
Jianao Zhang
Yinping Lu
Weixian Wang
Li Zhang
Ling Li
Fengqin Zhou
Jun Wang
Ulf Dittmer
Mengji Lu
Yu Hu
Dongliang Yang
Xin Zheng
Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients
EBioMedicine
Coronavirus
SARS-CoV-2
COVID-19
Lymphopenia
Inflammatory cytokine
author_facet Jing Liu
Sumeng Li
Jia Liu
Boyun Liang
Xiaobei Wang
Hua Wang
Wei Li
Qiaoxia Tong
Jianhua Yi
Lei Zhao
Lijuan Xiong
Chunxia Guo
Jin Tian
Jinzhuo Luo
Jinghong Yao
Ran Pang
Hui Shen
Cheng Peng
Ting Liu
Qian Zhang
Jun Wu
Ling Xu
Sihong Lu
Baoju Wang
Zhihong Weng
Chunrong Han
Huabing Zhu
Ruxia Zhou
Helong Zhou
Xiliu Chen
Pian Ye
Bin Zhu
Lu Wang
Wenqing Zhou
Shengsong He
Yongwen He
Shenghua Jie
Ping Wei
Jianao Zhang
Yinping Lu
Weixian Wang
Li Zhang
Ling Li
Fengqin Zhou
Jun Wang
Ulf Dittmer
Mengji Lu
Yu Hu
Dongliang Yang
Xin Zheng
author_sort Jing Liu
title Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients
title_short Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients
title_full Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients
title_fullStr Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients
title_full_unstemmed Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients
title_sort longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of sars-cov-2 infected patients
publisher Elsevier
series EBioMedicine
issn 2352-3964
publishDate 2020-05-01
description 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.
topic Coronavirus
SARS-CoV-2
COVID-19
Lymphopenia
Inflammatory cytokine
url http://www.sciencedirect.com/science/article/pii/S2352396420301389
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spelling doaj-9a8079b35d664c4dbeba115d1ce263302020-11-25T02:23:30ZengElsevierEBioMedicine2352-39642020-05-0155Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patientsJing Liu0Sumeng Li1Jia Liu2Boyun Liang3Xiaobei Wang4Hua Wang5Wei Li6Qiaoxia Tong7Jianhua Yi8Lei Zhao9Lijuan Xiong10Chunxia Guo11Jin Tian12Jinzhuo Luo13Jinghong Yao14Ran Pang15Hui Shen16Cheng Peng17Ting Liu18Qian Zhang19Jun Wu20Ling Xu21Sihong Lu22Baoju Wang23Zhihong Weng24Chunrong Han25Huabing Zhu26Ruxia Zhou27Helong Zhou28Xiliu Chen29Pian Ye30Bin Zhu31Lu Wang32Wenqing Zhou33Shengsong He34Yongwen He35Shenghua Jie36Ping Wei37Jianao Zhang38Yinping Lu39Weixian Wang40Li Zhang41Ling Li42Fengqin Zhou43Jun Wang44Ulf Dittmer45Mengji Lu46Yu Hu47Dongliang Yang48Xin Zheng49Department 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaDepartment 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, ChinaInstitute for Virology, University Hospital of Essen, University of Duisburg-Essen, Essen 45147, Germany; Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, ChinaInstitute for Virology, University Hospital of Essen, University of Duisburg-Essen, Essen 45147, Germany; Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, ChinaInstitute for Virology, University Hospital of Essen, University of Duisburg-Essen, Essen 45147, Germany; Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, ChinaDepartment of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Corresponding author.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; Corresponding authors at: Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.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; Corresponding authors at: Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.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.http://www.sciencedirect.com/science/article/pii/S2352396420301389CoronavirusSARS-CoV-2COVID-19LymphopeniaInflammatory cytokine