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

Identifieur interne : 000502 ( Main/Exploration ); précédent : 000501; suivant : 000503

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

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

Source :

RBID : PMC:7165294

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.


Url:
DOI: 10.1016/j.ebiom.2020.102763
PubMed: NONE
PubMed Central: 7165294


Affiliations:


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<name sortKey="Shen, Hui" sort="Shen, Hui" uniqKey="Shen H" first="Hui" last="Shen">Hui Shen</name>
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<author>
<name sortKey="Liu, Ting" sort="Liu, Ting" uniqKey="Liu T" first="Ting" last="Liu">Ting Liu</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<author>
<name sortKey="Zhang, Qian" sort="Zhang, Qian" uniqKey="Zhang Q" first="Qian" last="Zhang">Qian Zhang</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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</placeName>
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<author>
<name sortKey="Wu, Jun" sort="Wu, Jun" uniqKey="Wu J" first="Jun" last="Wu">Jun Wu</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<affiliation wicri:level="1">
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<settlement type="city">Wuhan</settlement>
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</placeName>
</affiliation>
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<author>
<name sortKey="Xu, Ling" sort="Xu, Ling" uniqKey="Xu L" first="Ling" last="Xu">Ling Xu</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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</placeName>
</affiliation>
</author>
<author>
<name sortKey="Lu, Sihong" sort="Lu, Sihong" uniqKey="Lu S" first="Sihong" last="Lu">Sihong Lu</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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</placeName>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<settlement type="city">Wuhan</settlement>
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</placeName>
</affiliation>
</author>
<author>
<name sortKey="Wang, Baoju" sort="Wang, Baoju" uniqKey="Wang B" first="Baoju" last="Wang">Baoju Wang</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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</placeName>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<settlement type="city">Wuhan</settlement>
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</placeName>
</affiliation>
</author>
<author>
<name sortKey="Weng, Zhihong" sort="Weng, Zhihong" uniqKey="Weng Z" first="Zhihong" last="Weng">Zhihong Weng</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Han, Chunrong" sort="Han, Chunrong" uniqKey="Han C" first="Chunrong" last="Han">Chunrong Han</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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</placeName>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
<placeName>
<settlement type="city">Wuhan</settlement>
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</placeName>
</affiliation>
</author>
<author>
<name sortKey="Zhu, Huabing" sort="Zhu, Huabing" uniqKey="Zhu H" first="Huabing" last="Zhu">Huabing Zhu</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
<placeName>
<settlement type="city">Wuhan</settlement>
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</placeName>
</affiliation>
</author>
<author>
<name sortKey="Zhou, Ruxia" sort="Zhou, Ruxia" uniqKey="Zhou R" first="Ruxia" last="Zhou">Ruxia Zhou</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<settlement type="city">Wuhan</settlement>
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</placeName>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<placeName>
<settlement type="city">Wuhan</settlement>
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</placeName>
</affiliation>
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<author>
<name sortKey="Zhou, Helong" sort="Zhou, Helong" uniqKey="Zhou H" first="Helong" last="Zhou">Helong Zhou</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
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<settlement type="city">Wuhan</settlement>
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</placeName>
</affiliation>
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<author>
<name sortKey="Chen, Xiliu" sort="Chen, Xiliu" uniqKey="Chen X" first="Xiliu" last="Chen">Xiliu Chen</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
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</placeName>
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<author>
<name sortKey="Ye, Pian" sort="Ye, Pian" uniqKey="Ye P" first="Pian" last="Ye">Pian Ye</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
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<wicri:regionArea>Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
<placeName>
<settlement type="city">Wuhan</settlement>
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</placeName>
</affiliation>
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<author>
<name sortKey="Zhu, Bin" sort="Zhu, Bin" uniqKey="Zhu B" first="Bin" last="Zhu">Bin Zhu</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
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<wicri:regionArea>Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<settlement type="city">Wuhan</settlement>
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</placeName>
</affiliation>
</author>
<author>
<name sortKey="Wang, Lu" sort="Wang, Lu" uniqKey="Wang L" first="Lu" last="Wang">Lu Wang</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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</placeName>
</affiliation>
</author>
<author>
<name sortKey="Zhou, Wenqing" sort="Zhou, Wenqing" uniqKey="Zhou W" first="Wenqing" last="Zhou">Wenqing Zhou</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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</placeName>
</affiliation>
</author>
<author>
<name sortKey="He, Shengsong" sort="He, Shengsong" uniqKey="He S" first="Shengsong" last="He">Shengsong He</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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</placeName>
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</author>
<author>
<name sortKey="He, Yongwen" sort="He, Yongwen" uniqKey="He Y" first="Yongwen" last="He">Yongwen He</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
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<author>
<name sortKey="Jie, Shenghua" sort="Jie, Shenghua" uniqKey="Jie S" first="Shenghua" last="Jie">Shenghua Jie</name>
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<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
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<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<name sortKey="Wei, Ping" sort="Wei, Ping" uniqKey="Wei P" first="Ping" last="Wei">Ping Wei</name>
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<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
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<title xml:lang="en" level="a" type="main">Longitudinal characteristics of lymphocyte responses and cytokine profiles in the peripheral blood of SARS-CoV-2 infected patients</title>
<author>
<name sortKey="Liu, Jing" sort="Liu, Jing" uniqKey="Liu J" first="Jing" last="Liu">Jing Liu</name>
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<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
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<author>
<name sortKey="Yi, Jianhua" sort="Yi, Jianhua" uniqKey="Yi J" first="Jianhua" last="Yi">Jianhua Yi</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<author>
<name sortKey="Zhao, Lei" sort="Zhao, Lei" uniqKey="Zhao L" first="Lei" last="Zhao">Lei Zhao</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<author>
<name sortKey="Xiong, Lijuan" sort="Xiong, Lijuan" uniqKey="Xiong L" first="Lijuan" last="Xiong">Lijuan Xiong</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<author>
<name sortKey="Guo, Chunxia" sort="Guo, Chunxia" uniqKey="Guo C" first="Chunxia" last="Guo">Chunxia Guo</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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</affiliation>
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<author>
<name sortKey="Tian, Jin" sort="Tian, Jin" uniqKey="Tian J" first="Jin" last="Tian">Jin Tian</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
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<author>
<name sortKey="Luo, Jinzhuo" sort="Luo, Jinzhuo" uniqKey="Luo J" first="Jinzhuo" last="Luo">Jinzhuo Luo</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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</affiliation>
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<author>
<name sortKey="Yao, Jinghong" sort="Yao, Jinghong" uniqKey="Yao J" first="Jinghong" last="Yao">Jinghong Yao</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<settlement type="city">Wuhan</settlement>
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</placeName>
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<author>
<name sortKey="Pang, Ran" sort="Pang, Ran" uniqKey="Pang R" first="Ran" last="Pang">Ran Pang</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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</placeName>
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<author>
<name sortKey="Shen, Hui" sort="Shen, Hui" uniqKey="Shen H" first="Hui" last="Shen">Hui Shen</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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</affiliation>
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</placeName>
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<author>
<name sortKey="Peng, Cheng" sort="Peng, Cheng" uniqKey="Peng C" first="Cheng" last="Peng">Cheng Peng</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
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<author>
<name sortKey="Liu, Ting" sort="Liu, Ting" uniqKey="Liu T" first="Ting" last="Liu">Ting Liu</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<country xml:lang="fr">République populaire de Chine</country>
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</placeName>
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<author>
<name sortKey="Zhang, Qian" sort="Zhang, Qian" uniqKey="Zhang Q" first="Qian" last="Zhang">Qian Zhang</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
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<wicri:regionArea>Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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</placeName>
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<author>
<name sortKey="Wu, Jun" sort="Wu, Jun" uniqKey="Wu J" first="Jun" last="Wu">Jun Wu</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
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<wicri:regionArea>Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<author>
<name sortKey="Xu, Ling" sort="Xu, Ling" uniqKey="Xu L" first="Ling" last="Xu">Ling Xu</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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</placeName>
</affiliation>
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<author>
<name sortKey="Lu, Sihong" sort="Lu, Sihong" uniqKey="Lu S" first="Sihong" last="Lu">Sihong Lu</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
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<author>
<name sortKey="Wang, Baoju" sort="Wang, Baoju" uniqKey="Wang B" first="Baoju" last="Wang">Baoju Wang</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
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</author>
<author>
<name sortKey="Weng, Zhihong" sort="Weng, Zhihong" uniqKey="Weng Z" first="Zhihong" last="Weng">Zhihong Weng</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<name sortKey="Han, Chunrong" sort="Han, Chunrong" uniqKey="Han C" first="Chunrong" last="Han">Chunrong Han</name>
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<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
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<name sortKey="Zhu, Huabing" sort="Zhu, Huabing" uniqKey="Zhu H" first="Huabing" last="Zhu">Huabing Zhu</name>
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<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
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<name sortKey="Zhou, Ruxia" sort="Zhou, Ruxia" uniqKey="Zhou R" first="Ruxia" last="Zhou">Ruxia Zhou</name>
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<name sortKey="Zhou, Helong" sort="Zhou, Helong" uniqKey="Zhou H" first="Helong" last="Zhou">Helong Zhou</name>
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<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<author>
<name sortKey="Chen, Xiliu" sort="Chen, Xiliu" uniqKey="Chen X" first="Xiliu" last="Chen">Xiliu Chen</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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</author>
<author>
<name sortKey="Ye, Pian" sort="Ye, Pian" uniqKey="Ye P" first="Pian" last="Ye">Pian Ye</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<author>
<name sortKey="Zhu, Bin" sort="Zhu, Bin" uniqKey="Zhu B" first="Bin" last="Zhu">Bin Zhu</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
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<settlement type="city">Wuhan</settlement>
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</placeName>
</affiliation>
</author>
<author>
<name sortKey="Wang, Lu" sort="Wang, Lu" uniqKey="Wang L" first="Lu" last="Wang">Lu Wang</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<settlement type="city">Wuhan</settlement>
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</placeName>
</affiliation>
</author>
<author>
<name sortKey="Zhou, Wenqing" sort="Zhou, Wenqing" uniqKey="Zhou W" first="Wenqing" last="Zhou">Wenqing Zhou</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<settlement type="city">Wuhan</settlement>
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</placeName>
</affiliation>
</author>
<author>
<name sortKey="He, Shengsong" sort="He, Shengsong" uniqKey="He S" first="Shengsong" last="He">Shengsong He</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<settlement type="city">Wuhan</settlement>
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</placeName>
</affiliation>
</author>
<author>
<name sortKey="He, Yongwen" sort="He, Yongwen" uniqKey="He Y" first="Yongwen" last="He">Yongwen He</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Jie, Shenghua" sort="Jie, Shenghua" uniqKey="Jie S" first="Shenghua" last="Jie">Shenghua Jie</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<settlement type="city">Wuhan</settlement>
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</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
<placeName>
<settlement type="city">Wuhan</settlement>
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</placeName>
</affiliation>
</author>
<author>
<name sortKey="Wei, Ping" sort="Wei, Ping" uniqKey="Wei P" first="Ping" last="Wei">Ping Wei</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<settlement type="city">Wuhan</settlement>
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</placeName>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<settlement type="city">Wuhan</settlement>
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</placeName>
</affiliation>
</author>
<author>
<name sortKey="Zhang, Jianao" sort="Zhang, Jianao" uniqKey="Zhang J" first="Jianao" last="Zhang">Jianao Zhang</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
<placeName>
<settlement type="city">Wuhan</settlement>
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</placeName>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
<placeName>
<settlement type="city">Wuhan</settlement>
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</placeName>
</affiliation>
</author>
<author>
<name sortKey="Lu, Yinping" sort="Lu, Yinping" uniqKey="Lu Y" first="Yinping" last="Lu">Yinping Lu</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<settlement type="city">Wuhan</settlement>
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<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<settlement type="city">Wuhan</settlement>
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</placeName>
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<author>
<name sortKey="Wang, Weixian" sort="Wang, Weixian" uniqKey="Wang W" first="Weixian" last="Wang">Weixian Wang</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<name sortKey="Zhang, Li" sort="Zhang, Li" uniqKey="Zhang L" first="Li" last="Zhang">Li Zhang</name>
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<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
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<name sortKey="Li, Ling" sort="Li, Ling" uniqKey="Li L" first="Ling" last="Li">Ling Li</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<author>
<name sortKey="Zhou, Fengqin" sort="Zhou, Fengqin" uniqKey="Zhou F" first="Fengqin" last="Zhou">Fengqin Zhou</name>
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<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
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<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
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<author>
<name sortKey="Wang, Jun" sort="Wang, Jun" uniqKey="Wang J" first="Jun" last="Wang">Jun Wang</name>
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<nlm:aff id="aff0002">Institute for Virology, University Hospital of Essen, University of Duisburg-Essen, Essen 45147, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Virology, University Hospital of Essen, University of Duisburg-Essen, Essen 45147</wicri:regionArea>
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<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<author>
<name sortKey="Dittmer, Ulf" sort="Dittmer, Ulf" uniqKey="Dittmer U" first="Ulf" last="Dittmer">Ulf Dittmer</name>
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<nlm:aff id="aff0002">Institute for Virology, University Hospital of Essen, University of Duisburg-Essen, Essen 45147, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
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<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
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<name sortKey="Lu, Mengji" sort="Lu, Mengji" uniqKey="Lu M" first="Mengji" last="Lu">Mengji Lu</name>
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<nlm:aff id="aff0002">Institute for Virology, University Hospital of Essen, University of Duisburg-Essen, Essen 45147, Germany</nlm:aff>
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<name sortKey="Hu, Yu" sort="Hu, Yu" uniqKey="Hu Y" first="Yu" last="Hu">Yu Hu</name>
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<nlm:aff id="aff0005">Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<name sortKey="Yang, Dongliang" sort="Yang, Dongliang" uniqKey="Yang D" first="Dongliang" last="Yang">Dongliang Yang</name>
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<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
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<wicri:regionArea>Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
<placeName>
<settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Zheng, Xin" sort="Zheng, Xin" uniqKey="Zheng X" first="Xin" last="Zheng">Xin Zheng</name>
<affiliation wicri:level="1">
<nlm:aff id="aff0001">Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
<placeName>
<settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
<affiliation wicri:level="1">
<nlm:aff id="aff0003">Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022, China</nlm:aff>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, Huazhong University of Science and Technology, Wuhan 430022</wicri:regionArea>
<placeName>
<settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
</analytic>
<series>
<title level="j">EBioMedicine</title>
<idno type="eISSN">2352-3964</idno>
<imprint>
<date when="2020">2020</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc>
<textClass></textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<sec>
<title>Background</title>
<p>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.</p>
</sec>
<sec>
<title>Methods</title>
<p>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.</p>
</sec>
<sec>
<title>Findings</title>
<p>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
<sup>+</sup>
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
<sup>+</sup>
T cell ratio (N8R) (AUC =0•94) were identified as powerful prognostic factors affecting the prognosis for severe COVID-19.</p>
</sec>
<sec>
<title>Interpretation</title>
<p>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.</p>
</sec>
<sec>
<title>Funding</title>
<p>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.</p>
</sec>
</div>
</front>
<back>
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</TEI>
<affiliations>
<list>
<country>
<li>Allemagne</li>
<li>République populaire de Chine</li>
</country>
<region>
<li>Hubei</li>
</region>
<settlement>
<li>Wuhan</li>
</settlement>
</list>
<tree>
<country name="République populaire de Chine">
<region name="Hubei">
<name sortKey="Liu, Jing" sort="Liu, Jing" uniqKey="Liu J" first="Jing" last="Liu">Jing Liu</name>
</region>
<name sortKey="Chen, Xiliu" sort="Chen, Xiliu" uniqKey="Chen X" first="Xiliu" last="Chen">Xiliu Chen</name>
<name sortKey="Chen, Xiliu" sort="Chen, Xiliu" uniqKey="Chen X" first="Xiliu" last="Chen">Xiliu Chen</name>
<name sortKey="Dittmer, Ulf" sort="Dittmer, Ulf" uniqKey="Dittmer U" first="Ulf" last="Dittmer">Ulf Dittmer</name>
<name sortKey="Guo, Chunxia" sort="Guo, Chunxia" uniqKey="Guo C" first="Chunxia" last="Guo">Chunxia Guo</name>
<name sortKey="Guo, Chunxia" sort="Guo, Chunxia" uniqKey="Guo C" first="Chunxia" last="Guo">Chunxia Guo</name>
<name sortKey="Han, Chunrong" sort="Han, Chunrong" uniqKey="Han C" first="Chunrong" last="Han">Chunrong Han</name>
<name sortKey="Han, Chunrong" sort="Han, Chunrong" uniqKey="Han C" first="Chunrong" last="Han">Chunrong Han</name>
<name sortKey="He, Shengsong" sort="He, Shengsong" uniqKey="He S" first="Shengsong" last="He">Shengsong He</name>
<name sortKey="He, Shengsong" sort="He, Shengsong" uniqKey="He S" first="Shengsong" last="He">Shengsong He</name>
<name sortKey="He, Yongwen" sort="He, Yongwen" uniqKey="He Y" first="Yongwen" last="He">Yongwen He</name>
<name sortKey="He, Yongwen" sort="He, Yongwen" uniqKey="He Y" first="Yongwen" last="He">Yongwen He</name>
<name sortKey="Hu, Yu" sort="Hu, Yu" uniqKey="Hu Y" first="Yu" last="Hu">Yu Hu</name>
<name sortKey="Jie, Shenghua" sort="Jie, Shenghua" uniqKey="Jie S" first="Shenghua" last="Jie">Shenghua Jie</name>
<name sortKey="Jie, Shenghua" sort="Jie, Shenghua" uniqKey="Jie S" first="Shenghua" last="Jie">Shenghua Jie</name>
<name sortKey="Li, Ling" sort="Li, Ling" uniqKey="Li L" first="Ling" last="Li">Ling Li</name>
<name sortKey="Li, Ling" sort="Li, Ling" uniqKey="Li L" first="Ling" last="Li">Ling Li</name>
<name sortKey="Li, Sumeng" sort="Li, Sumeng" uniqKey="Li S" first="Sumeng" last="Li">Sumeng Li</name>
<name sortKey="Li, Sumeng" sort="Li, Sumeng" uniqKey="Li S" first="Sumeng" last="Li">Sumeng Li</name>
<name sortKey="Li, Wei" sort="Li, Wei" uniqKey="Li W" first="Wei" last="Li">Wei Li</name>
<name sortKey="Li, Wei" sort="Li, Wei" uniqKey="Li W" first="Wei" last="Li">Wei Li</name>
<name sortKey="Liang, Boyun" sort="Liang, Boyun" uniqKey="Liang B" first="Boyun" last="Liang">Boyun Liang</name>
<name sortKey="Liang, Boyun" sort="Liang, Boyun" uniqKey="Liang B" first="Boyun" last="Liang">Boyun Liang</name>
<name sortKey="Liu, Jia" sort="Liu, Jia" uniqKey="Liu J" first="Jia" last="Liu">Jia Liu</name>
<name sortKey="Liu, Jia" sort="Liu, Jia" uniqKey="Liu J" first="Jia" last="Liu">Jia Liu</name>
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<name sortKey="Liu, Ting" sort="Liu, Ting" uniqKey="Liu T" first="Ting" last="Liu">Ting Liu</name>
<name sortKey="Liu, Ting" sort="Liu, Ting" uniqKey="Liu T" first="Ting" last="Liu">Ting Liu</name>
<name sortKey="Lu, Mengji" sort="Lu, Mengji" uniqKey="Lu M" first="Mengji" last="Lu">Mengji Lu</name>
<name sortKey="Lu, Sihong" sort="Lu, Sihong" uniqKey="Lu S" first="Sihong" last="Lu">Sihong Lu</name>
<name sortKey="Lu, Sihong" sort="Lu, Sihong" uniqKey="Lu S" first="Sihong" last="Lu">Sihong Lu</name>
<name sortKey="Lu, Yinping" sort="Lu, Yinping" uniqKey="Lu Y" first="Yinping" last="Lu">Yinping Lu</name>
<name sortKey="Lu, Yinping" sort="Lu, Yinping" uniqKey="Lu Y" first="Yinping" last="Lu">Yinping Lu</name>
<name sortKey="Luo, Jinzhuo" sort="Luo, Jinzhuo" uniqKey="Luo J" first="Jinzhuo" last="Luo">Jinzhuo Luo</name>
<name sortKey="Luo, Jinzhuo" sort="Luo, Jinzhuo" uniqKey="Luo J" first="Jinzhuo" last="Luo">Jinzhuo Luo</name>
<name sortKey="Pang, Ran" sort="Pang, Ran" uniqKey="Pang R" first="Ran" last="Pang">Ran Pang</name>
<name sortKey="Pang, Ran" sort="Pang, Ran" uniqKey="Pang R" first="Ran" last="Pang">Ran Pang</name>
<name sortKey="Peng, Cheng" sort="Peng, Cheng" uniqKey="Peng C" first="Cheng" last="Peng">Cheng Peng</name>
<name sortKey="Peng, Cheng" sort="Peng, Cheng" uniqKey="Peng C" first="Cheng" last="Peng">Cheng Peng</name>
<name sortKey="Shen, Hui" sort="Shen, Hui" uniqKey="Shen H" first="Hui" last="Shen">Hui Shen</name>
<name sortKey="Shen, Hui" sort="Shen, Hui" uniqKey="Shen H" first="Hui" last="Shen">Hui Shen</name>
<name sortKey="Tian, Jin" sort="Tian, Jin" uniqKey="Tian J" first="Jin" last="Tian">Jin Tian</name>
<name sortKey="Tian, Jin" sort="Tian, Jin" uniqKey="Tian J" first="Jin" last="Tian">Jin Tian</name>
<name sortKey="Tong, Qiaoxia" sort="Tong, Qiaoxia" uniqKey="Tong Q" first="Qiaoxia" last="Tong">Qiaoxia Tong</name>
<name sortKey="Tong, Qiaoxia" sort="Tong, Qiaoxia" uniqKey="Tong Q" first="Qiaoxia" last="Tong">Qiaoxia Tong</name>
<name sortKey="Wang, Baoju" sort="Wang, Baoju" uniqKey="Wang B" first="Baoju" last="Wang">Baoju Wang</name>
<name sortKey="Wang, Baoju" sort="Wang, Baoju" uniqKey="Wang B" first="Baoju" last="Wang">Baoju Wang</name>
<name sortKey="Wang, Hua" sort="Wang, Hua" uniqKey="Wang H" first="Hua" last="Wang">Hua Wang</name>
<name sortKey="Wang, Jun" sort="Wang, Jun" uniqKey="Wang J" first="Jun" last="Wang">Jun Wang</name>
<name sortKey="Wang, Lu" sort="Wang, Lu" uniqKey="Wang L" first="Lu" last="Wang">Lu Wang</name>
<name sortKey="Wang, Lu" sort="Wang, Lu" uniqKey="Wang L" first="Lu" last="Wang">Lu Wang</name>
<name sortKey="Wang, Weixian" sort="Wang, Weixian" uniqKey="Wang W" first="Weixian" last="Wang">Weixian Wang</name>
<name sortKey="Wang, Weixian" sort="Wang, Weixian" uniqKey="Wang W" first="Weixian" last="Wang">Weixian Wang</name>
<name sortKey="Wang, Xiaobei" sort="Wang, Xiaobei" uniqKey="Wang X" first="Xiaobei" last="Wang">Xiaobei Wang</name>
<name sortKey="Wei, Ping" sort="Wei, Ping" uniqKey="Wei P" first="Ping" last="Wei">Ping Wei</name>
<name sortKey="Wei, Ping" sort="Wei, Ping" uniqKey="Wei P" first="Ping" last="Wei">Ping Wei</name>
<name sortKey="Weng, Zhihong" sort="Weng, Zhihong" uniqKey="Weng Z" first="Zhihong" last="Weng">Zhihong Weng</name>
<name sortKey="Weng, Zhihong" sort="Weng, Zhihong" uniqKey="Weng Z" first="Zhihong" last="Weng">Zhihong Weng</name>
<name sortKey="Wu, Jun" sort="Wu, Jun" uniqKey="Wu J" first="Jun" last="Wu">Jun Wu</name>
<name sortKey="Wu, Jun" sort="Wu, Jun" uniqKey="Wu J" first="Jun" last="Wu">Jun Wu</name>
<name sortKey="Xiong, Lijuan" sort="Xiong, Lijuan" uniqKey="Xiong L" first="Lijuan" last="Xiong">Lijuan Xiong</name>
<name sortKey="Xiong, Lijuan" sort="Xiong, Lijuan" uniqKey="Xiong L" first="Lijuan" last="Xiong">Lijuan Xiong</name>
<name sortKey="Xu, Ling" sort="Xu, Ling" uniqKey="Xu L" first="Ling" last="Xu">Ling Xu</name>
<name sortKey="Xu, Ling" sort="Xu, Ling" uniqKey="Xu L" first="Ling" last="Xu">Ling Xu</name>
<name sortKey="Yang, Dongliang" sort="Yang, Dongliang" uniqKey="Yang D" first="Dongliang" last="Yang">Dongliang Yang</name>
<name sortKey="Yang, Dongliang" sort="Yang, Dongliang" uniqKey="Yang D" first="Dongliang" last="Yang">Dongliang Yang</name>
<name sortKey="Yao, Jinghong" sort="Yao, Jinghong" uniqKey="Yao J" first="Jinghong" last="Yao">Jinghong Yao</name>
<name sortKey="Yao, Jinghong" sort="Yao, Jinghong" uniqKey="Yao J" first="Jinghong" last="Yao">Jinghong Yao</name>
<name sortKey="Ye, Pian" sort="Ye, Pian" uniqKey="Ye P" first="Pian" last="Ye">Pian Ye</name>
<name sortKey="Ye, Pian" sort="Ye, Pian" uniqKey="Ye P" first="Pian" last="Ye">Pian Ye</name>
<name sortKey="Yi, Jianhua" sort="Yi, Jianhua" uniqKey="Yi J" first="Jianhua" last="Yi">Jianhua Yi</name>
<name sortKey="Yi, Jianhua" sort="Yi, Jianhua" uniqKey="Yi J" first="Jianhua" last="Yi">Jianhua Yi</name>
<name sortKey="Zhang, Jianao" sort="Zhang, Jianao" uniqKey="Zhang J" first="Jianao" last="Zhang">Jianao Zhang</name>
<name sortKey="Zhang, Jianao" sort="Zhang, Jianao" uniqKey="Zhang J" first="Jianao" last="Zhang">Jianao Zhang</name>
<name sortKey="Zhang, Li" sort="Zhang, Li" uniqKey="Zhang L" first="Li" last="Zhang">Li Zhang</name>
<name sortKey="Zhang, Li" sort="Zhang, Li" uniqKey="Zhang L" first="Li" last="Zhang">Li Zhang</name>
<name sortKey="Zhang, Qian" sort="Zhang, Qian" uniqKey="Zhang Q" first="Qian" last="Zhang">Qian Zhang</name>
<name sortKey="Zhang, Qian" sort="Zhang, Qian" uniqKey="Zhang Q" first="Qian" last="Zhang">Qian Zhang</name>
<name sortKey="Zhao, Lei" sort="Zhao, Lei" uniqKey="Zhao L" first="Lei" last="Zhao">Lei Zhao</name>
<name sortKey="Zhao, Lei" sort="Zhao, Lei" uniqKey="Zhao L" first="Lei" last="Zhao">Lei Zhao</name>
<name sortKey="Zheng, Xin" sort="Zheng, Xin" uniqKey="Zheng X" first="Xin" last="Zheng">Xin Zheng</name>
<name sortKey="Zheng, Xin" sort="Zheng, Xin" uniqKey="Zheng X" first="Xin" last="Zheng">Xin Zheng</name>
<name sortKey="Zhou, Fengqin" sort="Zhou, Fengqin" uniqKey="Zhou F" first="Fengqin" last="Zhou">Fengqin Zhou</name>
<name sortKey="Zhou, Fengqin" sort="Zhou, Fengqin" uniqKey="Zhou F" first="Fengqin" last="Zhou">Fengqin Zhou</name>
<name sortKey="Zhou, Helong" sort="Zhou, Helong" uniqKey="Zhou H" first="Helong" last="Zhou">Helong Zhou</name>
<name sortKey="Zhou, Helong" sort="Zhou, Helong" uniqKey="Zhou H" first="Helong" last="Zhou">Helong Zhou</name>
<name sortKey="Zhou, Ruxia" sort="Zhou, Ruxia" uniqKey="Zhou R" first="Ruxia" last="Zhou">Ruxia Zhou</name>
<name sortKey="Zhou, Ruxia" sort="Zhou, Ruxia" uniqKey="Zhou R" first="Ruxia" last="Zhou">Ruxia Zhou</name>
<name sortKey="Zhou, Wenqing" sort="Zhou, Wenqing" uniqKey="Zhou W" first="Wenqing" last="Zhou">Wenqing Zhou</name>
<name sortKey="Zhou, Wenqing" sort="Zhou, Wenqing" uniqKey="Zhou W" first="Wenqing" last="Zhou">Wenqing Zhou</name>
<name sortKey="Zhu, Bin" sort="Zhu, Bin" uniqKey="Zhu B" first="Bin" last="Zhu">Bin Zhu</name>
<name sortKey="Zhu, Bin" sort="Zhu, Bin" uniqKey="Zhu B" first="Bin" last="Zhu">Bin Zhu</name>
<name sortKey="Zhu, Huabing" sort="Zhu, Huabing" uniqKey="Zhu H" first="Huabing" last="Zhu">Huabing Zhu</name>
<name sortKey="Zhu, Huabing" sort="Zhu, Huabing" uniqKey="Zhu H" first="Huabing" last="Zhu">Huabing Zhu</name>
</country>
<country name="Allemagne">
<noRegion>
<name sortKey="Wang, Jun" sort="Wang, Jun" uniqKey="Wang J" first="Jun" last="Wang">Jun Wang</name>
</noRegion>
<name sortKey="Dittmer, Ulf" sort="Dittmer, Ulf" uniqKey="Dittmer U" first="Ulf" last="Dittmer">Ulf Dittmer</name>
<name sortKey="Lu, Mengji" sort="Lu, Mengji" uniqKey="Lu M" first="Mengji" last="Lu">Mengji Lu</name>
</country>
</tree>
</affiliations>
</record>

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