Cargando…

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

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 metab...

Descripción completa

Detalles Bibliográficos
Autores principales: Ceperuelo-Mallafré, Victòria, Reverté, Laia, Peraire, Joaquim, Madeira, Ana, Maymó-Masip, Elsa, López-Dupla, Miguel, Gutierrez-Valencia, Alicia, Ruiz-Mateos, Ezequiel, Buzón, Maria José, Jorba, Rosa, Vendrell, Joan, Auguet, Teresa, Olona, Montserrat, Vidal, Francesc, Rull, Anna, Fernández-Veledo, Sonia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9515795/
https://www.ncbi.nlm.nih.gov/pubmed/36189213
http://dx.doi.org/10.3389/fimmu.2022.912579
_version_ 1784798567061258240
author Ceperuelo-Mallafré, Victòria
Reverté, Laia
Peraire, Joaquim
Madeira, Ana
Maymó-Masip, Elsa
López-Dupla, Miguel
Gutierrez-Valencia, Alicia
Ruiz-Mateos, Ezequiel
Buzón, Maria José
Jorba, Rosa
Vendrell, Joan
Auguet, Teresa
Olona, Montserrat
Vidal, Francesc
Rull, Anna
Fernández-Veledo, Sonia
author_facet Ceperuelo-Mallafré, Victòria
Reverté, Laia
Peraire, Joaquim
Madeira, Ana
Maymó-Masip, Elsa
López-Dupla, Miguel
Gutierrez-Valencia, Alicia
Ruiz-Mateos, Ezequiel
Buzón, Maria José
Jorba, Rosa
Vendrell, Joan
Auguet, Teresa
Olona, Montserrat
Vidal, Francesc
Rull, Anna
Fernández-Veledo, Sonia
author_sort Ceperuelo-Mallafré, Victòria
collection PubMed
description 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.
format Online
Article
Text
id pubmed-9515795
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-95157952022-09-29 Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes Ceperuelo-Mallafré, Victòria Reverté, Laia Peraire, Joaquim Madeira, Ana Maymó-Masip, Elsa López-Dupla, Miguel Gutierrez-Valencia, Alicia Ruiz-Mateos, Ezequiel Buzón, Maria José Jorba, Rosa Vendrell, Joan Auguet, Teresa Olona, Montserrat Vidal, Francesc Rull, Anna Fernández-Veledo, Sonia Front Immunol Immunology 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. Frontiers Media S.A. 2022-09-14 /pmc/articles/PMC9515795/ /pubmed/36189213 http://dx.doi.org/10.3389/fimmu.2022.912579 Text en Copyright © 2022 Ceperuelo-Mallafré, Reverté, Peraire, Madeira, Maymó-Masip, López-Dupla, Gutierrez-Valencia, Ruiz-Mateos, Buzón, Jorba, Vendrell, Auguet, Olona, Vidal, Rull and Fernández-Veledo https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Ceperuelo-Mallafré, Victòria
Reverté, Laia
Peraire, Joaquim
Madeira, Ana
Maymó-Masip, Elsa
López-Dupla, Miguel
Gutierrez-Valencia, Alicia
Ruiz-Mateos, Ezequiel
Buzón, Maria José
Jorba, Rosa
Vendrell, Joan
Auguet, Teresa
Olona, Montserrat
Vidal, Francesc
Rull, Anna
Fernández-Veledo, Sonia
Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes
title Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes
title_full Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes
title_fullStr Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes
title_full_unstemmed Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes
title_short Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes
title_sort circulating pyruvate is a potent prognostic marker for critical covid-19 outcomes
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9515795/
https://www.ncbi.nlm.nih.gov/pubmed/36189213
http://dx.doi.org/10.3389/fimmu.2022.912579
work_keys_str_mv AT ceperuelomallafrevictoria circulatingpyruvateisapotentprognosticmarkerforcriticalcovid19outcomes
AT revertelaia circulatingpyruvateisapotentprognosticmarkerforcriticalcovid19outcomes
AT perairejoaquim circulatingpyruvateisapotentprognosticmarkerforcriticalcovid19outcomes
AT madeiraana circulatingpyruvateisapotentprognosticmarkerforcriticalcovid19outcomes
AT maymomasipelsa circulatingpyruvateisapotentprognosticmarkerforcriticalcovid19outcomes
AT lopezduplamiguel circulatingpyruvateisapotentprognosticmarkerforcriticalcovid19outcomes
AT gutierrezvalenciaalicia circulatingpyruvateisapotentprognosticmarkerforcriticalcovid19outcomes
AT ruizmateosezequiel circulatingpyruvateisapotentprognosticmarkerforcriticalcovid19outcomes
AT buzonmariajose circulatingpyruvateisapotentprognosticmarkerforcriticalcovid19outcomes
AT jorbarosa circulatingpyruvateisapotentprognosticmarkerforcriticalcovid19outcomes
AT vendrelljoan circulatingpyruvateisapotentprognosticmarkerforcriticalcovid19outcomes
AT auguetteresa circulatingpyruvateisapotentprognosticmarkerforcriticalcovid19outcomes
AT olonamontserrat circulatingpyruvateisapotentprognosticmarkerforcriticalcovid19outcomes
AT vidalfrancesc circulatingpyruvateisapotentprognosticmarkerforcriticalcovid19outcomes
AT rullanna circulatingpyruvateisapotentprognosticmarkerforcriticalcovid19outcomes
AT fernandezveledosonia circulatingpyruvateisapotentprognosticmarkerforcriticalcovid19outcomes