%0 Journal Article
%A Gómez Delgado, Irene
%A López Pastor, Andrea R.
%A González Jiménez, Adela
%A Ramos Acosta, Carlos
%A Hernández Garate, Yenitzeh
%A Martínez Micaelo, Neus
%A Amigó, Núria
%A Espino Paisán, Laura
%A Anguita Mandly, Eduardo Luis
%A Urcelay, Elena
%T Long-term mitochondrial and metabolic impairment in lymphocytes of subjects who recovered after severe COVID-19
%D 2025
%@ 1573-6822
%U https://hdl.handle.net/20.500.14352/115373
%X 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.
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