Статья

Elevated Exhaustion Levels of NK and CD8+ T Cells as Indicators for Progression and Prognosis of COVID-19 Disease

M. Li, W. Guo, Y. Dong, X. Wang, D. Dai, X. Liu, Y. Wu, M. Li, W. Zhang, H. Zhou, Z. Zhang, L. Lin, Z. Kang, T. Yu, C. Tian, R. Qin, Y. Gui, F. Jiang, H. Fan, V. Heissmeyer, A. Sarapultsev, L. Wang, S. Luo, D. Hu,
2021

Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) induced Coronavirus Disease 2019 (COVID-19) has posed a global threat to public health. The immune system is crucial in defending and eliminating the virus and infected cells. However, immune dysregulation may result in the rapid progression of COVID-19. Here, we evaluated the subsets, phenotypic and functional characteristics of natural killer (NK) and T cells in patients with COVID-19 and their associations with disease severity. Methods: Demographic and clinical data of COVID-19 patients enrolled in Wuhan Union Hospital from February 25 to February 27, 2020, were collected and analyzed. The phenotypic and functional characteristics of NK cells and T cells subsets in circulating blood and serum levels of cytokines were analyzed via flow cytometry. Then the LASSO logistic regression model was employed to predict risk factors for the severity of COVID-19. Results: The counts and percentages of NK cells, CD4+ T cells, CD8+ T cells and NKT cells were significantly reduced in patients with severe symptoms. The cytotoxic CD3-CD56dimCD16+ cell population significantly decreased, while the CD3-CD56dimCD16- part significantly increased in severe COVID-19 patients. More importantly, elevated expression of regulatory molecules, such as CD244 and programmed death-1 (PD-1), on NK cells and T cells, as well as decreased serum cytotoxic effector molecules including perforin and granzyme A, were detected in patients with COVID-19. The serum IL-6, IL-10, and TNF-α were significantly increased in severe patients. Moreover, the CD3-CD56dimCD16- cells were screened out as an influential factor in severe cases by LASSO logistic regression. Conclusions: The functional exhaustion and other subset alteration of NK and T cells may contribute to the progression and improve the prognosis of COVID-19. Surveillance of lymphocyte subsets may in the future enable early screening for signs of critical illness and understanding the pathogenesis of this disease. © Copyright © 2020 Li, Guo, Dong, Wang, Dai, Liu, Wu, Li, Zhang, Zhou, Zhang, Lin, Kang, Yu, Tian, Qin, Gui, Jiang, Fan, Heissmeyer, Sarapultsev, Wang, Luo and Hu.

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  • 1. Version of Record от 2021-04-27

Метаданные

Об авторах
  • M. Li
    Department of Integrated Traditional Chinese and Western Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • W. Guo
    Department of Clinical Laboratory, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • Y. Dong
    Key Laboratory of Molecular Biophysics of the Ministry of Education, Hubei Key Laboratory of Bioinformatics and Molecular-Imaging, Department of Bioinformatics and Systems Biology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China
  • X. Wang
    HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
  • D. Dai
    Department of Gastroenterology, Henan Provincial People’s Hospital, Zhengzhou, China
  • X. Liu
    Department of Paediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • Y. Wu
    Tianjin University of Traditional Chinese Medicine, Tianjin, China
  • M. Li
    Institute for Immunology, Ludwig-Maximilians-Universität München, Munich, Germany
  • W. Zhang
    Institute of Molecular Immunology, Helmholtz Zentrum München, Munich, Germany
  • H. Zhou
    Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Science, Ekaterinburg, Russian Federation
  • Z. Zhang
    Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
  • L. Lin
  • Z. Kang
  • T. Yu
  • C. Tian
  • R. Qin
  • Y. Gui
  • F. Jiang
  • H. Fan
  • V. Heissmeyer
  • A. Sarapultsev
  • L. Wang
  • S. Luo
  • D. Hu
Название журнала
  • Frontiers in Immunology
Том
  • 11
Страницы
  • -
Ключевые слова
  • C reactive protein; CD27 antigen; CD56 antigen; CD8 antigen; creatinine; cystatin C; D dimer; gamma interferon; granzyme A; granzyme B; hemoglobin; interleukin 10; interleukin 17; interleukin 2; interleukin 4; interleukin 6; perforin; troponin; tumor necrosis factor; adult; Article; CD4+ T lymphocyte; clinical article; controlled study; coronavirus disease 2019; disease severity; erythrocyte sedimentation rate; female; flow cytometry; gene frequency; hospitalization; human; immune response; male; natural killer cell; neutrophil count; neutrophil lymphocyte ratio; oxygen saturation; peripheral blood mononuclear cell; regulatory T lymphocyte; retrospective study; risk factor; RNA extraction; treatment response; aged; blood; CD8+ T lymphocyte; China; cytology; epidemiology; genetics; immunology; leukocyte count; middle aged; pandemic; physiology; prognosis; T lymphocyte subpopulation; virology; Adult; Aged; CD8-Positive T-Lymphocytes; China; COVID-19; Female; Flow Cytometry; Humans; Killer Cells, Natural; Leukocyte Count; Male; Middle Aged; Pandemics; Prognosis; SARS-CoV-2; T-Lymphocyte Subsets
Издатель
  • Frontiers Media S.A.
Тип документа
  • journal article
Тип лицензии Creative Commons
  • CC
Правовой статус документа
  • Свободная лицензия
Источник
  • scopus