Gómez Delgado, IreneLópez Pastor, Andrea R.González Jiménez, AdelaRamos Acosta, CarlosHernández Garate, YenitzehMartínez Micaelo, NeusAmigó, NúriaEspino Paisán, LauraAnguita Mandly, Eduardo LuisUrcelay, Elena2025-01-212025-01-212025-01-10Gómez-Delgado, I., López-Pastor, A.R., González-Jiménez, A. et al. Long-term mitochondrial and metabolic impairment in lymphocytes of subjects who recovered after severe COVID-19. Cell Biol Toxicol 41, 27 (2025). https://doi.org/10.1007/s10565-024-09976-01573-682210.1007/s10565-024-09976-0https://hdl.handle.net/20.500.14352/115373The underlying mechanisms explaining the differential course of SARS-CoV-2 infection and the potential clinical consequences after COVID-19 resolution have not been fully elucidated. As a dysregulated mitochondrial activity could impair the immune response, we explored long-lasting changes in mitochondrial functionality, circulating cytokine levels, and metabolomic profiles of infected individuals after symptoms resolution, to evaluate whether a complete recovery could be achieved. Results of this pilot study evidenced that different parameters of aerobic respiration in lymphocytes of individuals recuperated from a severe course lagged behind those shown upon mild COVID-19 recovery, in basal conditions and after simulated reinfection, and they also showed altered glycolytic capacity. The severe groups showed trends to enhanced superoxide production in parallel to lower OPA1-S levels. Unbalance of pivotal mitochondrial fusion (MFN2, OPA1) and fission (DRP1, FIS1) proteins was detected, suggesting a disruption in mitochondrial dynamics, as well as a lack of structural integrity in the electron transport chain. In serum, altered cytokine levels of IL-1β, IFN-α2, and IL-27 persisted long after clinical recovery, and growing amounts of the latter after severe infection correlated with lower basal and maximal respiration, ATP production, and glycolytic capacity. Finally, a trend for higher circulating levels of 3-hydroxybutyrate was found in individuals recovered after severe compared to mild course. In summary, long after acute infection, mitochondrial and metabolic changes seem to differ in a situation of full recovery after mild infection versus the one evolving from severe infection.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/journal articlehttps://doi.org/10.1007/s10565-024-09976-0https://link.springer.com/article/10.1007/s10565-024-09976-0open access616.98:578.834578.834:616.98MitocondriaCOVID-19LinfocitosMetabolismoSecuelaMedicina32 Ciencias Médicas