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Publications

Journal Article Research Support, Non-U.S. Gov't Epublish 16 citations

PubMed: 36189213 DOI: 10.3389/fimmu.2022.912579

Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes.

Front Immunol 13:912579

Authors: Victòria Ceperuelo-Mallafré, Laia Reverté, Joaquim Peraire, Ana Madeira, Elsa Maymó-Masip, Miguel López-Dupla, Alicia Gutierrez-Valencia, Ezequiel Ruiz-Mateos, Maria José Buzón, Rosa Jorba, Joan Vendrell, Teresa Auguet, Montserrat Olona, Francesc Vidal, Anna Rull, Sonia Fernández-Veledo

Affiliations

  • Universitat Rovira i Virgili (URV), Tarragona, Spain.
  • Institut Investigació Sanitària Pere Virgili (IISPV), Tarragona, Spain.
  • CIBER de Diabetes y Enfermedades Metaboílicas Asociadas (CIBERDEM)-Instituto de Salud Carlos III, Madrid, Spain.
  • CIBER Enfermedades Infecciosas (CIBERINFEC)-Instituto de Salud Carlos III, Madrid, Spain.
  • Hospital Universitari de Tarragona Joan XXIII (HJ23), Tarragona, Spain.
  • Clinical Unit of Infectious Diseases, Microbiology and Preventive Medicine, Institute of Biomedicine of Seville (IBiS), Virgen del Rocío University Hospital, Consejo Superior de Investigaciones Científicas (CSIC), University of Seville, Seville, Spain.
  • Infectious Diseases Department, Vall d'Hebron Institute of Research (VHIR), Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, (VHIR) Task Force COVID-19, Barcelona, Spain.

Abstract

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 that fluorometric quantification of circulating pyruvate is a cost-effective clinical decision support tool to improve patient stratification and prognosis prediction.

MeSH

Infections, Immune System Diseases, C-Reactive Protein, Serum, Covid-19, Sars-Cov-2

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