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Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes
COVID-19; Cuantificación fluorométrica; Piruvato ; COVID-19; Quantificació fluoromètrica; Piruvat ; COVID-19; Fluorometric quantification; Pyruvate ; Background: 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. Methods: 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. Results: 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<0.05). The combined strategy proposed herein enabled us to establish that circulating pyruvate levels (p<0.001) together with body mass index (p=0.025), C-reactive protein (p=0.039), D-Dimer (p<0.001) and creatinine (p=0.043) levels, are independent predictors of critical COVID-19. Furthermore, classification and regression tree (CART) analysis provided a cut-off value of pyruvate in serum (24.54 µM; p<0.001) as an early criterion to accurately classify patients with critical outcomes. Conclusion: Our findings support the link between COVID-19 pathogenesis and immunometabolic dysregulation, and show ...
Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes
COVID-19; Cuantificación fluorométrica; Piruvato ; COVID-19; Quantificació fluoromètrica; Piruvat ; COVID-19; Fluorometric quantification; Pyruvate ; Background: 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. Methods: 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. Results: 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<0.05). The combined strategy proposed herein enabled us to establish that circulating pyruvate levels (p<0.001) together with body mass index (p=0.025), C-reactive protein (p=0.039), D-Dimer (p<0.001) and creatinine (p=0.043) levels, are independent predictors of critical COVID-19. Furthermore, classification and regression tree (CART) analysis provided a cut-off value of pyruvate in serum (24.54 µM; p<0.001) as an early criterion to accurately classify patients with critical outcomes. Conclusion: Our findings support the link between COVID-19 pathogenesis and immunometabolic dysregulation, and show ...
Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes
Ceperuelo Mallafré, Victòria (Autor:in) / Reverté Calvet, Laia (Autor:in) / Peraire, Joaquim (Autor:in) / Madeira, Ana (Autor:in) / Maymó Masip, Elsa (Autor:in) / López-Dupla, Miguel (Autor:in) / Buzón Gómez, María José (Autor:in) / Institut Català de la Salut / Ceperuelo-Mallafré V Universitat Rovira i Virgili (URV), Tarragona, Spain. Institut Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)- Instituto de Salud Carlos III, Madrid, Spain. Reverté L Institut Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain. CIBER Enfermedades Infecciosas (CIBERINFEC)- Instituto de Salud Carlos III, Madrid, Spain. Peraire J, López-Dupla M Universitat Rovira i Virgili (URV), Tarragona, Spain. Institut Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain. CIBER Enfermedades Infecciosas (CIBERINFEC)- Instituto de Salud Carlos III, Madrid, Spain. Hospital Universitari de Tarragona Joan XXIII (HJ23), Tarragona, Spain. Madeira A, Maymó-Masip E Institut Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain. CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM)- Instituto de Salud Carlos III, Madrid, Spain. Buzón MJ Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Servei de Malalties Infeccioses, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain / Vall d'Hebron Barcelona Hospital Campus
14.09.2022
000861817200001
Scientia
Aufsatz (Zeitschrift)
Elektronische Ressource
Englisch
Marcadors bioquímics , DISEASES::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections , ENFERMEDADES::virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus , CHEMICALS AND DRUGS::Biological Factors::Biomarkers , TÉCNICAS Y EQUIPOS ANALÍTICOS , DIAGNOSTIC AND THERAPEUTIC TECHNIQUES , CHEMICALS AND DRUGS::Organic Chemicals::Carboxylic Acids::Keto Acids::Pyruvates::Pyruvic Acid , DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico , AND EQUIPMENT::Diagnosis::Prognosis , COMPUESTOS QUÍMICOS Y DROGAS::compuestos orgánicos::ácidos carboxílicos::cetoácidos::piruvatos::ácido pirúvico , Prognosi , COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores , COVID-19 (Malaltia) , ANALYTICAL
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