Ceballos, Francisco CVirseda-Berdices, AnaResino, SalvadorRyan, PabloMartínez-González, OscarPerez-Garcia, FelipeMartin-Vicente, MariaBrochado-Kith, OscarBlancas, RafaelBartolomé-Sánchez, SofíaVidal-Alcántara, Erick JoanAlbóniga-Díez, Oihane ElenaCuadros-González, JuanBlanca-López, NataliaMartinez, IsidoroRamirez Martinez-Acitores, IgnacioBarbas, CoralFernandez-Rodriguez, AmandaJimenez-Sousa, Maria Angeles2022-11-182022-11-182022-06-30Front Immunol. 2022 Jun 30;13:925558.http://hdl.handle.net/20.500.12105/15186Background: metabolic changes through SARS-CoV-2 infection has been reported but not fully comprehended. This metabolic dysregulation affects multiple organs during COVID-19 and its early detection can be used as a prognosis marker of severity. Therefore, we aimed to characterize metabolic and cytokine profile at COVID-19 onset and its relationship with disease severity to identify metabolic profiles predicting disease progression. Material and methods: we performed a retrospective cross-sectional study in 123 COVID-19 patients which were stratified as asymptomatic/mild, moderate and severe according to the highest COVID-19 severity status, and a group of healthy controls. We performed an untargeted plasma metabolic profiling (gas chromatography and capillary electrophoresis-mass spectrometry (GC and CE-MS)) and cytokine evaluation. Results: After data filtering and identification we observed 105 metabolites dysregulated (66 GC-MS and 40 CE-MS) which shown different expression patterns for each COVID-19 severity status. These metabolites belonged to different metabolic pathways including amino acid, energy, and nitrogen metabolism among others. Severity-specific metabolic dysregulation was observed, as an increased transformation of L-tryptophan into L-kynurenine. Thus, metabolic profiling at hospital admission differentiate between severe and moderate patients in the later phase of worse evolution. Several plasma pro-inflammatory biomarkers showed significant correlation with deregulated metabolites, specially with L-kynurenine and L-tryptophan. Finally, we describe a strong sex-related dysregulation of metabolites, cytokines and chemokines between severe and moderate patients. In conclusion, metabolic profiling of COVID-19 patients at disease onset is a powerful tool to unravel the SARS-CoV-2 molecular pathogenesis. Conclusions: This technique makes it possible to identify metabolic phenoconversion that predicts disease progression and explains the pronounced pathogenesis differences between sexes.engVoRhttp://creativecommons.org/licenses/by/4.0/COVID-19MetabolomicsSeveritySex-specificSpanish hospitalsDisease onsetCOVID-19Cross-Sectional StudiesCytokinesDisease ProgressionFemaleHumansKynurenineMaleRetrospective StudiesSARS-CoV-2Severity of Illness IndexTryptophanAtribución 4.0 Internacional358446151392555810.3389/fimmu.2022.9255581664-3224Frontiers in immunologyopen access