Mitochondrial Dysfunction Associates With Acute T Lymphocytopenia and Impaired Functionality in COVID-19 Patients.

Autor:	Mo Y; AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., To KK; AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.; Center for Virology, Vaccinology and Therapeutics, Health@InnoHK, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.; Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China., Zhou R; AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Liu L; AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Cao T; AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Huang H; AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Du Z; AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Lim CYH; AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Yim LY; AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Luk TY; AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Chan JM; Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong, Hong Kong SAR, China., Chik TS; Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong, Hong Kong SAR, China., Lau DP; Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong, Hong Kong SAR, China., Tsang OT; Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong, Hong Kong SAR, China., Tam AR; Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Hung IF; Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China., Yuen KY; AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.; Center for Virology, Vaccinology and Therapeutics, Health@InnoHK, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.; Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China., Chen Z; AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.; Center for Virology, Vaccinology and Therapeutics, Health@InnoHK, The University of Hong Kong, Hong Kong, Hong Kong SAR, China.; Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Jan 14; Vol. 12, pp. 799896. Date of Electronic Publication: 2022 Jan 14 (Print Publication: 2021).
DOI:	10.3389/fimmu.2021.799896
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Mo, To, Zhou, Liu, Cao, Huang, Du, Lim, Yim, Luk, Chan, Chik, Lau, Tsang, Tam, Hung, Yuen and Chen.)
Databáze:	MEDLINE
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