tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Kelvin Kai-Wang To[SUP] 1 2 3 4 [/SUP], Runhong Zhou[SUP] 1 [/SUP], Li Liu[SUP] 1 [/SUP], Tianyu Cao[SUP] 1 [/SUP], Haode Huang[SUP] 1 [/SUP], Zhenglong Du[SUP] 1 [/SUP], Chun Yu Hubert Lim[SUP] 1 [/SUP], Lok-Yan Yim[SUP] 1 [/SUP], Tsz-Yat Luk[SUP] 1 [/SUP], Jacky Man-Chun Chan[SUP] 5 [/SUP], Thomas Shiu-Hong Chik[SUP] 5 [/SUP], Daphne Pui-Ling Lau[SUP] 5 [/SUP], Owen Tak-Yin Tsang[SUP] 5 [/SUP], Anthony Raymond Tam[SUP] 6 [/SUP], Ivan Fan-Ngai Hung[SUP] 6 [/SUP], Kwok-Yung Yuen[SUP] 1 2 3 4 [/SUP], Zhiwei Chen[SUP] 1 2 3 4 [/SUP]
Affiliations
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).
. 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[SUP] 1 [/SUP], Kelvin Kai-Wang To[SUP] 1 2 3 4 [/SUP], Runhong Zhou[SUP] 1 [/SUP], Li Liu[SUP] 1 [/SUP], Tianyu Cao[SUP] 1 [/SUP], Haode Huang[SUP] 1 [/SUP], Zhenglong Du[SUP] 1 [/SUP], Chun Yu Hubert Lim[SUP] 1 [/SUP], Lok-Yan Yim[SUP] 1 [/SUP], Tsz-Yat Luk[SUP] 1 [/SUP], Jacky Man-Chun Chan[SUP] 5 [/SUP], Thomas Shiu-Hong Chik[SUP] 5 [/SUP], Daphne Pui-Ling Lau[SUP] 5 [/SUP], Owen Tak-Yin Tsang[SUP] 5 [/SUP], Anthony Raymond Tam[SUP] 6 [/SUP], Ivan Fan-Ngai Hung[SUP] 6 [/SUP], Kwok-Yung Yuen[SUP] 1 2 3 4 [/SUP], Zhiwei Chen[SUP] 1 2 3 4 [/SUP]
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).