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

Frontiers in Immunology, Vol. 12 (2022)

Keywords
Authors
  • Yufei Mo
  • AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Kelvin Kai-Wang To
  • AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Kelvin Kai-Wang To
  • State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Kelvin Kai-Wang To
  • Center for Virology, Vaccinology and Therapeutics, [email protected], The University of Hong Kong, Hong Kong, Hong Kong SAR, China
  • Kelvin Kai-Wang To
  • Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
  • Runhong Zhou
  • AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Li Liu
  • AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Tianyu Cao
  • AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Haode Huang
  • AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Zhenglong Du
  • AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Chun Yu Hubert Lim
  • AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Lok-Yan Yim
  • AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Tsz-Yat Luk
  • AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Jacky Man-Chun Chan
  • Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong, Hong Kong SAR, China
  • Thomas Shiu-Hong Chik
  • Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong, Hong Kong SAR, China
  • Daphne Pui-Ling Lau
  • Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong, Hong Kong SAR, China
  • Owen Tak-Yin Tsang
  • Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong, Hong Kong SAR, China
  • Anthony Raymond Tam
  • Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Ivan Fan-Ngai Hung
  • Department of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Kwok-Yung Yuen
  • AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Kwok-Yung Yuen
  • State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Kwok-Yung Yuen
  • Center for Virology, Vaccinology and Therapeutics, [email protected], The University of Hong Kong, Hong Kong, Hong Kong SAR, China
  • Kwok-Yung Yuen
  • Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
  • Zhiwei Chen
  • AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Zhiwei Chen
  • State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
  • Zhiwei Chen
  • Center for Virology, Vaccinology and Therapeutics, [email protected], The University of Hong Kong, Hong Kong, Hong Kong SAR, China
  • Zhiwei Chen
  • Department of Clinical Microbiology and Infection Control, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China

Abstract

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.

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