Ceperuelo-Mallafre, VictoriaReverte, LaiaPeraire, JoaquimMadeira, AnaMaymo-Masip, ElsaLopez-Dupla, MiguelGutierrez-Valencia, AliciaRuiz-Mateos, EzequielBuzon, Maria JoseJorba, RosaVendrell, JoanAuguet, TeresaOlona, MontserratVidal, FrancescRull, AnnaFernandez-Veledo, Sonia2023-05-032023-05-032022-09-14Ceperuelo-Mallafré V, Reverté L, Peraire J, Madeira A, Maymó-Masip E, López-Dupla M, et al. Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes. Front Immunol. 2022 Sep 14;13:912579.http://hdl.handle.net/10668/20589Coronavirus-19 (COVID-19) disease is driven by an unchecked immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus which alters host mitochondrial-associated mechanisms. Compromised mitochondrial health results in abnormal reprogramming of glucose metabolism, which can disrupt extracellular signalling. We hypothesized that examining mitochondrial energy-related signalling metabolites implicated in host immune response to SARS-CoV-2 infection would provide potential biomarkers for predicting the risk of severe COVID-19 illness. We used a semi-targeted serum metabolomics approach in 273 patients with different severity grades of COVID-19 recruited at the acute phase of the infection to determine the relative abundance of tricarboxylic acid (Krebs) cycle-related metabolites with known extracellular signaling properties (pyruvate, lactate, succinate and α-ketoglutarate). Abundance levels of energy-related metabolites were evaluated in a validation cohort (n=398) using quantitative fluorimetric assays. Increased levels of four energy-related metabolites (pyruvate, lactate, a-ketoglutarate and succinate) were found in critically ill COVID-19 patients using semi-targeted and targeted approaches (p Our findings support the link between COVID-19 pathogenesis and immunometabolic dysregulation, and show that fluorometric quantification of circulating pyruvate is a cost-effective clinical decision support tool to improve patient stratification and prognosis prediction.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/COVID-19energy-related metabolitesfluorometric quantificationpyruvatesemi-targeted metebolomicsBiomarkersC-Reactive ProteinCOVID-19CreatinineGlucoseHumansKetoglutaric AcidsLactatesPrognosisPyruvic AcidSARS-CoV-2SuccinatesTricarboxylic Acidsresearch article36189213open accessPacientesInmunidadCoronavirusBiomarcadoresPronósticoGlucosaSueroVirusMetabolómicaInfeccionesMetabolismo10.3389/fimmu.2022.9125791664-3224PMC9515795https://www.frontiersin.org/articles/10.3389/fimmu.2022.912579/pdfhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9515795/pdf