%0 Journal Article %A Ceperuelo-Mallafre, Victoria %A Reverte, Laia %A Peraire, Joaquim %A Madeira, Ana %A Maymo-Masip, Elsa %A Lopez-Dupla, Miguel %A Gutierrez-Valencia, Alicia %A Ruiz-Mateos, Ezequiel %A Buzon, Maria Jose %A Jorba, Rosa %A Vendrell, Joan %A Auguet, Teresa %A Olona, Montserrat %A Vidal, Francesc %A Rull, Anna %A Fernandez-Veledo, Sonia %T Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes. %D 2022 %U http://hdl.handle.net/10668/20589 %X Coronavirus-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. %K COVID-19 %K energy-related metabolites %K fluorometric quantification %K pyruvate %K semi-targeted metebolomics %~