1. Aberrant hyperactivation of cytotoxic T-cell as a potential determinant of COVID-19 severity
- Author
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Myoung Don Oh, Gi Chan Han, Pyoeng Gyun Choe, Wan Beom Park, Kyoung Ho Song, Gwanghun Kim, Eu Suk Kim, Chang Kyung Kang, Hong Bin Kim, Hyun Mu Shin, Hang Rae Kim, Nam Joong Kim, and Minji Kim
- Subjects
CD4-Positive T-Lymphocytes ,Male ,0301 basic medicine ,Programmed Cell Death 1 Receptor ,severity ,CD8-Positive T-Lymphocytes ,Lymphocyte Activation ,Granzymes ,0302 clinical medicine ,granzyme B ,Cytotoxic T cell ,Medicine ,030212 general & internal medicine ,perforin ,Aged, 80 and over ,Immunity, Cellular ,education.field_of_study ,biology ,General Medicine ,Middle Aged ,Infectious Diseases ,Cytokines ,Female ,Coronavirus Infections ,Adult ,Microbiology (medical) ,Pneumonia, Viral ,030106 microbiology ,Population ,macromolecular substances ,Peripheral blood mononuclear cell ,Article ,lcsh:Infectious and parasitic diseases ,Betacoronavirus ,03 medical and health sciences ,Immune system ,Humans ,lcsh:RC109-216 ,Lymphocyte Count ,education ,Pandemics ,Aged ,SARS-CoV-2 ,business.industry ,COVID-19 ,contraction ,Granzyme B ,Ki-67 Antigen ,Perforin ,Granzyme ,Immunology ,Leukocytes, Mononuclear ,biology.protein ,business ,CD8 ,cytotoxic T cell ,T-Lymphocytes, Cytotoxic - Abstract
Highlights • COVID-19 can deteriorate at the 2nd week of illness despite of decreasing viral loads • We analyzed PBMCs of severe or mild COVID-19 cases at the 1st and 3rd week of illness • Cellular responses were not different between two groups at the 1st week of illness • Higher T-cell proliferation, activation, and cytotoxicity was noted in severe cases at the 3rd week • Aberrant hyperactivation of cytotoxic T-cell may contribute to severe COVID-19 pneumonia, Objectives We hypothesized that immune response may contribute to progression of coronavirus disease-19 (COVID-19) at the second week of illness. Therefore, we compared cell-mediated immune (CMI) responses between severe and mild COVID-19 cases. Methods We examined peripheral blood mononuclear cells of laboratory-confirmed COVID-19 patients from their first and third weeks of illness. Severe pneumonia was defined as an oxygen saturation ≤ 93% at room air. Expressions of molecules related to T-cell activation and functions were analyzed by flow cytometry. Results The population dynamics of T cells at the first week were not different between the two groups. However, total numbers of CD4+ and CD8 + T cells tended to be lower in the severe group at the third week of illness. Expressions of Ki-67, PD-1, perforin, and granzyme B in CD4+ or CD8+ T cells were significantly higher in the severe group than in the mild group at the third week. In contrast to the mild group, the levels of their expression did not decrease in severe group. Conclusions Severe COVID-19 had higher degree of proliferation, activation, and cytotoxicity of T-cells at the late phase of illness without cytotoxic T-cell contraction, which might contribute to the development of severe COVID-19.
- Published
- 2020