Reinforcing the Evidence of Mitochondrial Dysfunction in Long COVID Patients Using a Multiplatform Mass Spectrometry-Based Metabolomics Approach

Despite the recent and increasing knowledge surrounding
COVID-19
infection, the underlying mechanisms of the persistence of symptoms
for a long time after the acute infection are still not completely
understood. Here, a multiplatform mass spectrometry-based approach
was used for metabolomic and lipidomic profiling of human plasma samples
from Long COVID patients (n = 40) to reveal mitochondrial
dysfunction when compared with individuals fully recovered from acute
mild COVID-19 (n = 40). Untargeted metabolomic analysis
using CE-ESI(+/−)-TOF-MS and GC-Q-MS was performed. Additionally,
a lipidomic analysis using LC-ESI(+/−)-QTOF-MS based on an
in-house library revealed 447 lipid species identified with a high
confidence annotation level. The integration of complementary analytical
platforms has allowed a comprehensive metabolic and lipidomic characterization
of plasma alterations in Long COVID disease that found 46 relevant
metabolites which allowed to discriminate between Long COVID and fully
recovered patients. We report specific metabolites altered in Long
COVID, mainly related to a decrease in the amino acid metabolism and
ceramide plasma levels and an increase in the tricarboxylic acid (TCA)
cycle, reinforcing the evidence of an impaired mitochondrial function.
The most relevant alterations shown in this study will help to better
understand the insights of Long COVID syndrome by providing a deeper
knowledge of the metabolomic basis of the pathology.