RT Journal Article T1 Long-term mitochondrial and metabolic impairment in lymphocytes of subjects who recovered after severe COVID-19 A1 Gómez Delgado, Irene A1 López Pastor, Andrea R. A1 González Jiménez, Adela A1 Ramos Acosta, Carlos A1 Hernández Garate, Yenitzeh A1 Martínez Micaelo, Neus A1 Amigó, Núria A1 Espino Paisán, Laura A1 Anguita Mandly, Eduardo Luis A1 Urcelay, Elena AB The 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. PB Springer SN 1573-6822 YR 2025 FD 2025-01-10 LK https://hdl.handle.net/20.500.14352/115373 UL https://hdl.handle.net/20.500.14352/115373 LA eng NO Gómez-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/s10565-024-09976-0 DS Docta Complutense RD 4 abr 2025