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

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Front Immunol


. 2022 Jan 14;12:799896.
doi: 10.3389/fimmu.2021.799896. eCollection 2021.
Mitochondrial Dysfunction Associates With Acute T Lymphocytopenia and Impaired Functionality in COVID-19 Patients


Yufei Mo ¹ , Kelvin Kai-Wang To ^{1 2 3 4} , Runhong Zhou ¹ , Li Liu ¹ , Tianyu Cao ¹ , Haode Huang ¹ , Zhenglong Du ¹ , Chun Yu Hubert Lim ¹ , Lok-Yan Yim ¹ , Tsz-Yat Luk ¹ , Jacky Man-Chun Chan ⁵ , Thomas Shiu-Hong Chik ⁵ , Daphne Pui-Ling Lau ⁵ , Owen Tak-Yin Tsang ⁵ , Anthony Raymond Tam ⁶ , Ivan Fan-Ngai **** ⁶ , Kwok-Yung Yuen ^{1 2 3 4} , Zhiwei Chen ^{1 2 3 4}



Affiliations

• PMID: 35095881
• PMCID: PMC8795605
• DOI: 10.3389/fimmu.2021.799896

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.

Keywords: COVID-19; SARS-CoV-2; T-cell functionality; memory T cell; mitochondrial dysfunction (MD).