Frontiers in Immunology (Sep 2022)

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

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

DOI
https://doi.org/10.3389/fimmu.2022.912579
Journal volume & issue
Vol. 13

Abstract

Read online

BackgroundCoronavirus-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.MethodsWe 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.ResultsIncreased 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.ConclusionOur 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.

Keywords