Mitochondrial Dysfunction Associates With Acute T Lymphocytopenia and Impaired Functionality in COVID-19 Patients
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in rapid T lymphocytopenia and functional impairment of T cells. The underlying mechanism, however, remains incompletely understood. In this study, we focused on characterizing the phenotype and kinetics of T-cell subsets...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.799896/full |
| _version_ | 1818965631063556096 |
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| author | Yufei Mo Kelvin Kai-Wang To Kelvin Kai-Wang To Kelvin Kai-Wang To Kelvin Kai-Wang To Runhong Zhou Li Liu Tianyu Cao Haode Huang Zhenglong Du Chun Yu Hubert Lim Lok-Yan Yim Tsz-Yat Luk Jacky Man-Chun Chan Thomas Shiu-Hong Chik Daphne Pui-Ling Lau Owen Tak-Yin Tsang Anthony Raymond Tam Ivan Fan-Ngai Hung Kwok-Yung Yuen Kwok-Yung Yuen Kwok-Yung Yuen Kwok-Yung Yuen Zhiwei Chen Zhiwei Chen Zhiwei Chen Zhiwei Chen |
| author_facet | Yufei Mo Kelvin Kai-Wang To Kelvin Kai-Wang To Kelvin Kai-Wang To Kelvin Kai-Wang To Runhong Zhou Li Liu Tianyu Cao Haode Huang Zhenglong Du Chun Yu Hubert Lim Lok-Yan Yim Tsz-Yat Luk Jacky Man-Chun Chan Thomas Shiu-Hong Chik Daphne Pui-Ling Lau Owen Tak-Yin Tsang Anthony Raymond Tam Ivan Fan-Ngai Hung Kwok-Yung Yuen Kwok-Yung Yuen Kwok-Yung Yuen Kwok-Yung Yuen Zhiwei Chen Zhiwei Chen Zhiwei Chen Zhiwei Chen |
| author_sort | Yufei Mo |
| collection | DOAJ |
| description | Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in rapid T lymphocytopenia and functional impairment of T cells. The underlying mechanism, however, remains incompletely understood. In this study, we focused on characterizing the phenotype and kinetics of T-cell subsets with mitochondrial dysfunction (MD) by multicolor flow cytometry and investigating the association between MD and T-cell functionality. While 73.9% of study subjects displayed clinical lymphocytopenia upon hospital admission, a significant reduction of CD4 or CD8 T-cell frequency was found in all asymptomatic, symptomatic, and convalescent cases. CD4 and CD8 T cells with increased MD were found in both asymptomatic and symptomatic patients within the first week of symptom onset. Lower proportion of memory CD8 T cell with MD was found in severe patients than in mild ones at the stage of disease progression. Critically, the frequency of T cells with MD in symptomatic patients was preferentially associated with CD4 T-cell loss and CD8 T-cell hyperactivation, respectively. Patients bearing effector memory CD4 and CD8 T cells with the phenotype of high MD exhibited poorer T-cell responses upon either phorbol 12-myristate-13-acetate (PMA)/ionomycin or SARS-CoV-2 peptide stimulation than those with low MD. Our findings demonstrated an MD-associated mechanism underlying SARS-CoV-2-induced T lymphocytopenia and functional impairment during the acute phase of infection. |
| first_indexed | 2024-12-20T13:20:04Z |
| format | Article |
| id | doaj.art-847b178133554300bd35131d3ec55877 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-20T13:20:04Z |
| publishDate | 2022-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-847b178133554300bd35131d3ec558772022-12-21T19:39:25ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-01-011210.3389/fimmu.2021.799896799896Mitochondrial Dysfunction Associates With Acute T Lymphocytopenia and Impaired Functionality in COVID-19 PatientsYufei Mo0Kelvin Kai-Wang To1Kelvin Kai-Wang To2Kelvin Kai-Wang To3Kelvin Kai-Wang To4Runhong Zhou5Li Liu6Tianyu Cao7Haode Huang8Zhenglong Du9Chun Yu Hubert Lim10Lok-Yan Yim11Tsz-Yat Luk12Jacky Man-Chun Chan13Thomas Shiu-Hong Chik14Daphne Pui-Ling Lau15Owen Tak-Yin Tsang16Anthony Raymond Tam17Ivan Fan-Ngai Hung18Kwok-Yung Yuen19Kwok-Yung Yuen20Kwok-Yung Yuen21Kwok-Yung Yuen22Zhiwei Chen23Zhiwei Chen24Zhiwei Chen25Zhiwei Chen26AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, ChinaAIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, ChinaState Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong SAR, ChinaCenter for Virology, Vaccinology and Therapeutics, Health@InnoHK, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, ChinaAIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, ChinaAIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, ChinaAIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, ChinaAIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, ChinaAIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, ChinaAIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, ChinaAIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, ChinaAIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, ChinaDepartment of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong, Hong Kong SAR, ChinaDepartment of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong, Hong Kong SAR, ChinaDepartment of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong, Hong Kong SAR, ChinaDepartment of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong, Hong Kong SAR, ChinaDepartment of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, ChinaDepartment of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, ChinaAIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, ChinaState Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong SAR, ChinaCenter for Virology, Vaccinology and Therapeutics, Health@InnoHK, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, ChinaAIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, ChinaState Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong SAR, ChinaCenter for Virology, Vaccinology and Therapeutics, Health@InnoHK, The University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, ChinaSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection results in rapid T lymphocytopenia and functional impairment of T cells. The underlying mechanism, however, remains incompletely understood. In this study, we focused on characterizing the phenotype and kinetics of T-cell subsets with mitochondrial dysfunction (MD) by multicolor flow cytometry and investigating the association between MD and T-cell functionality. While 73.9% of study subjects displayed clinical lymphocytopenia upon hospital admission, a significant reduction of CD4 or CD8 T-cell frequency was found in all asymptomatic, symptomatic, and convalescent cases. CD4 and CD8 T cells with increased MD were found in both asymptomatic and symptomatic patients within the first week of symptom onset. Lower proportion of memory CD8 T cell with MD was found in severe patients than in mild ones at the stage of disease progression. Critically, the frequency of T cells with MD in symptomatic patients was preferentially associated with CD4 T-cell loss and CD8 T-cell hyperactivation, respectively. Patients bearing effector memory CD4 and CD8 T cells with the phenotype of high MD exhibited poorer T-cell responses upon either phorbol 12-myristate-13-acetate (PMA)/ionomycin or SARS-CoV-2 peptide stimulation than those with low MD. Our findings demonstrated an MD-associated mechanism underlying SARS-CoV-2-induced T lymphocytopenia and functional impairment during the acute phase of infection.https://www.frontiersin.org/articles/10.3389/fimmu.2021.799896/fullmitochondrial dysfunction (MD)T-cell functionalitymemory T cellSARS-CoV-2COVID-19 |
| spellingShingle | Yufei Mo Kelvin Kai-Wang To Kelvin Kai-Wang To Kelvin Kai-Wang To Kelvin Kai-Wang To Runhong Zhou Li Liu Tianyu Cao Haode Huang Zhenglong Du Chun Yu Hubert Lim Lok-Yan Yim Tsz-Yat Luk Jacky Man-Chun Chan Thomas Shiu-Hong Chik Daphne Pui-Ling Lau Owen Tak-Yin Tsang Anthony Raymond Tam Ivan Fan-Ngai Hung Kwok-Yung Yuen Kwok-Yung Yuen Kwok-Yung Yuen Kwok-Yung Yuen Zhiwei Chen Zhiwei Chen Zhiwei Chen Zhiwei Chen Mitochondrial Dysfunction Associates With Acute T Lymphocytopenia and Impaired Functionality in COVID-19 Patients Frontiers in Immunology mitochondrial dysfunction (MD) T-cell functionality memory T cell SARS-CoV-2 COVID-19 |
| title | Mitochondrial Dysfunction Associates With Acute T Lymphocytopenia and Impaired Functionality in COVID-19 Patients |
| title_full | Mitochondrial Dysfunction Associates With Acute T Lymphocytopenia and Impaired Functionality in COVID-19 Patients |
| title_fullStr | Mitochondrial Dysfunction Associates With Acute T Lymphocytopenia and Impaired Functionality in COVID-19 Patients |
| title_full_unstemmed | Mitochondrial Dysfunction Associates With Acute T Lymphocytopenia and Impaired Functionality in COVID-19 Patients |
| title_short | Mitochondrial Dysfunction Associates With Acute T Lymphocytopenia and Impaired Functionality in COVID-19 Patients |
| title_sort | mitochondrial dysfunction associates with acute t lymphocytopenia and impaired functionality in covid 19 patients |
| topic | mitochondrial dysfunction (MD) T-cell functionality memory T cell SARS-CoV-2 COVID-19 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.799896/full |
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