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Article

Impaired Peripheral Blood Mononuclear Cell (PBMC) Mitochondrial Respiration Is Associated with Mortality and Long COVID Syndrome Severity in COVID-19 Patients

by
Anne-Laure Charles
1,
Léa Debrut
1,
Walid Oulehri
1,2,
Véronique Vincent
3,
Héloise Delagreverie
4,5,
Pauline Asael
1,
Marianne Riou
1,3,
Margherita Giannini
1,3,
Alain Meyer
1,3 and
Bernard Geny
1,3,*
1
Biomedicine Research Center of Strasbourg (CRBS), UR 3072, “Mitochondria, Oxidative Stress and Muscle Plasticity”, Faculty of Medicine, University of Strasbourg, 67081 Strasbourg, France
2
Department of Anesthesia and Intensive Care, Strasbourg University Hospital, 67091 Strasbourg, France
3
Department of Physiology and Functional Exploration, Strasbourg University Hospital, 67091 Strasbourg, France
4
Department of Clinical Microbiology, Hôpital Avicenne AP-HP, 125 rue de Stalingrad, 93000 Bobigny, France
5
Faculté de Médecine, INSERM U1137 IAME, Université Sorbonne Paris Nord and Université Paris Cité, 16 rue Henri Huchard, 75018 Paris, France
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(21), 10377; https://doi.org/10.3390/ijms262110377
Submission received: 2 October 2025 / Revised: 17 October 2025 / Accepted: 21 October 2025 / Published: 24 October 2025
(This article belongs to the Special Issue Molecular Research and Insights into COVID-19: Third Edition)
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Abstract

COVID-19 is a public health issue with a significant mortality rate and potential long-lasting disabling symptoms responsible for the long-COVID syndrome. Mitochondrial dysfunction is a key mechanism but whether peripheral blood mononuclear cell (PBMC) mitochondrial respiration changes might be associated with mortality and/or occurrence and severity of long-COVID syndrome remains to be investigated. We determined mitochondrial respiratory chain oxygen consumption in twenty COVID-19 patients hospitalized in the intensive care unit and analyzed their remaining symptoms at the third year after hospital release. PBMC mitochondrial respiration was decreased in COVID-19 patients compared to the control group (14.13 ± 2.35 vs. 6.21 ± 0.88 pmol/s/106 cell, p = 0.0006 for the OXPHOS state by CII). Considering COVID severity, such a decrease was greater in long-COVID patients and in patients who deceased (4.91 ± 0.75, p = 0.008 and 4.94 ± 1.11 pmol/s/106 cell, p = 0.04, respectively). PBMC markers of inflammation also increased with the severity of COVID (1.0 ± 0.08 vs. 14.45 ± 2.07, p = 0.02 for ISG15 in patients who died) and ISG15 negatively correlated with PBMC mitochondrial respiration (r = −0.67, p = 0.02 for CII). In conclusion, this study shows that the greater the impairment in PBMC mitochondrial respiration in patients hospitalized in the intensive care unit for COVID-19, the greater the mortality rate and the more severe the long-COVID symptoms—three years after hospital discharge. Further, PBMC markers of inflammation also increased with the severity of COVID and ISG15 negatively correlated with PBMC mitochondrial respiration. These results support that PBMC mitochondrial respiration might be a biomarker of COVID severity and further studies investigating whether modulation of PBMC mitochondrial respiration might improve COVID-19 patients’ prognosis.
Keywords: COVID; long COVID; peripheral blood mononuclear cells (PBMC); mitochondria; mitochondrial respiration; inflammation COVID; long COVID; peripheral blood mononuclear cells (PBMC); mitochondria; mitochondrial respiration; inflammation

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MDPI and ACS Style

Charles, A.-L.; Debrut, L.; Oulehri, W.; Vincent, V.; Delagreverie, H.; Asael, P.; Riou, M.; Giannini, M.; Meyer, A.; Geny, B. Impaired Peripheral Blood Mononuclear Cell (PBMC) Mitochondrial Respiration Is Associated with Mortality and Long COVID Syndrome Severity in COVID-19 Patients. Int. J. Mol. Sci. 2025, 26, 10377. https://doi.org/10.3390/ijms262110377

AMA Style

Charles A-L, Debrut L, Oulehri W, Vincent V, Delagreverie H, Asael P, Riou M, Giannini M, Meyer A, Geny B. Impaired Peripheral Blood Mononuclear Cell (PBMC) Mitochondrial Respiration Is Associated with Mortality and Long COVID Syndrome Severity in COVID-19 Patients. International Journal of Molecular Sciences. 2025; 26(21):10377. https://doi.org/10.3390/ijms262110377

Chicago/Turabian Style

Charles, Anne-Laure, Léa Debrut, Walid Oulehri, Véronique Vincent, Héloise Delagreverie, Pauline Asael, Marianne Riou, Margherita Giannini, Alain Meyer, and Bernard Geny. 2025. "Impaired Peripheral Blood Mononuclear Cell (PBMC) Mitochondrial Respiration Is Associated with Mortality and Long COVID Syndrome Severity in COVID-19 Patients" International Journal of Molecular Sciences 26, no. 21: 10377. https://doi.org/10.3390/ijms262110377

APA Style

Charles, A.-L., Debrut, L., Oulehri, W., Vincent, V., Delagreverie, H., Asael, P., Riou, M., Giannini, M., Meyer, A., & Geny, B. (2025). Impaired Peripheral Blood Mononuclear Cell (PBMC) Mitochondrial Respiration Is Associated with Mortality and Long COVID Syndrome Severity in COVID-19 Patients. International Journal of Molecular Sciences, 26(21), 10377. https://doi.org/10.3390/ijms262110377

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