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      Analysis of mitochondrial function in lymphocytes obtained from COVID-19 patients

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          Abstract

          Objectives

          There is a significant decline in the lymphocyte subset counts in the peripheral blood of COVID-19 patients. However, the mitochondrial function of lymphocytes obtained from COVID-19 patients has rarely been studied.

          Methods

          A case-control study was conducted in 115 COVID-19 patients and 50 healthy controls from December 2022 to February 2023. The extent of lymphocytic mitochondrial damage in these patients using mitochondrial fluorescence staining and flow cytometry. Clinical symptoms were evaluated using the SOFA and APACHE II scores.

          Results

          The mitochondrial function of lymphocytes was severely impaired in the peripheral blood of COVID-19 patients, compared to healthy controls, and was characterized by an increased single-cell mitochondrial mass (SCMM) and increased percentage of low mitochondrial membrane potential. The increase in the SCMM of T cells was more notable in patients with severe COVID-19 and was positively correlated with the SOFA and APACHE II scores. When the SCMM-CD8 cutoff value was 38.775, the AUC for distinguishing between severe and mild COVID-19 was 0.740, and the sensitivity, specificity, and Youden index were 65.8%, 82.1%, and 0.478, respectively.

          Conclusion

          SCMM-CD8 could act as a diagnostic biomarker of COVID-19 progression. However, this needs to be verified in other multi-center studies with a larger sample size.

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          Most cited references24

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          The role of mitochondria in reactive oxygen species metabolism and signaling.

          Oxidative stress is considered a major contributor to the etiology of both "normal" senescence and severe pathologies with serious public health implications. Several cellular sources, including mitochondria, are known to produce significant amounts of reactive oxygen species (ROS) that may contribute to intracellular oxidative stress. Mitochondria possess at least 10 known sites that are capable of generating ROS, but they also feature a sophisticated multilayered ROS defense system that is much less studied. This review summarizes the current knowledge about major components involved in mitochondrial ROS metabolism and factors that regulate ROS generation and removal at the level of mitochondria. An integrative systemic approach is applied to analysis of mitochondrial ROS metabolism, which is "dissected" into ROS generation, ROS emission, and ROS scavenging. The in vitro ROS-producing capacity of several mitochondrial sites is compared in the metabolic context and the role of mitochondria in ROS-dependent intracellular signaling is discussed.
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            Metabolic reprogramming is required for antibody production that is suppressed in anergic but exaggerated in chronically BAFF-exposed B cells.

            B cell activation leads to proliferation and Ab production that can protect from pathogens or promote autoimmunity. Regulation of cell metabolism is essential to support the demands of lymphocyte growth and effector function and may regulate tolerance. In this study, we tested the regulation and role of glucose uptake and metabolism in the proliferation and Ab production of control, anergic, and autoimmune-prone B cells. Control B cells had a balanced increase in lactate production and oxygen consumption following activation, with proportionally increased glucose transporter Glut1 expression and mitochondrial mass upon either LPS or BCR stimulation. This contrasted with metabolic reprogramming of T cells, which had lower glycolytic flux when resting but disproportionately increased this pathway upon activation. Importantly, tolerance greatly affected B cell metabolic reprogramming. Anergic B cells remained metabolically quiescent, with only a modest increase in glycolysis and oxygen consumption with LPS stimulation. B cells chronically stimulated with elevated BAFF, however, rapidly increased glycolysis and Ab production upon stimulation. Induction of glycolysis was critical for Ab production, as glycolytic inhibition with the pyruvate dehydrogenase kinase inhibitor dichloroacetate sharply suppressed B cell proliferation and Ab secretion in vitro and in vivo. Furthermore, B cell-specific deletion of Glut1 led to reduced B cell numbers and impaired Ab production in vivo. Together, these data show that activated B cells require Glut1-dependent metabolic reprogramming to support proliferation and Ab production that is distinct from T cells and that this glycolytic reprogramming is regulated in tolerance.
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              Mitochondria and microbiota dysfunction in COVID-19 pathogenesis

              Highlights • Mitochondria are the hub of cellular oxidative homeostasis. • Mitochondria are the major source of reactive oxygen species (ROS). • Extracellular mitochondria are found in blood, in circulating platelets and vesicles. • COVID-19 pathogenesis is aggravated by the hyper- inflammatory state. • Inflammation activates events leading to microbiota & mitochondrial oxidative damage. • Mitochondrial damage contributes to coagulopathy, ferroptosis & microbial dysbiosis. • Blood & platelet mitochondria dysfunction may accelerate systemic coagulopathy events. • Targeting mitochondria dysfunction may provide useful therapeutic strategies against COVID-19 pathogenesis.
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                Author and article information

                Journal
                Int J Immunopathol Pharmacol
                Int J Immunopathol Pharmacol
                spiji
                IJI
                International Journal of Immunopathology and Pharmacology
                SAGE Publications (Sage UK: London, England )
                0394-6320
                2058-7384
                27 October 2023
                Jan-Dec 2023
                : 37
                : 03946320231210736
                Affiliations
                [1 ]Center of Clinical Laboratory Medicine, Zhongda Hospital, Ringgold 162752, universitySoutheast University; , Nanjing, China
                [2 ]Department of Emergency and Critical Care Medicine, Zhongda Hospital, Ringgold 162752, universitySoutheast University; , Nanjing, China
                Author notes
                [*]Zhi He, Center of Clinical Laboratory Medicine, Zhongda Hospital, Southeast University, 87 Ding Jiaqiao, Nanjing 210009, China. Email: hezhi1125@ 123456163.com
                Author information
                https://orcid.org/0000-0001-7216-837X
                Article
                10.1177_03946320231210736
                10.1177/03946320231210736
                10612433
                37889851
                2332a03e-0fb0-462e-a5d0-b234e1d57e15
                © The Author(s) 2023

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 13 May 2023
                : 12 October 2023
                Categories
                Original Research Article
                Custom metadata
                ts10
                January-December 2023

                covid-19,single-cell mitochondrial mass,biomarker,lymphocyte subsets

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