Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers

The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report alterations in the plasma metabolome reflecting the clinical presentation of COVID-19 patients with mild (ambulatory) diseases, moderate disease (radiological...

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Published inCell death & disease Vol. 12; no. 3; pp. 258 - 11
Main Authors Danlos, François-Xavier, Grajeda-Iglesias, Claudia, Durand, Sylvère, Sauvat, Allan, Roumier, Mathilde, Cantin, Delphine, Colomba, Emeline, Rohmer, Julien, Pommeret, Fanny, Baciarello, Giulia, Willekens, Christophe, Vasse, Marc, Griscelli, Frank, Fahrner, Jean-Eudes, Goubet, Anne-Gaëlle, Dubuisson, Agathe, Derosa, Lisa, Nirmalathasan, Nitharsshini, Bredel, Delphine, Mouraud, Séverine, Pradon, Caroline, Stoclin, Annabelle, Rozenberg, Flore, Duchemin, Jérôme, Jourdi, Georges, Ellouze, Syrine, Levavasseur, Françoise, Albigès, Laurence, Soria, Jean-Charles, Barlesi, Fabrice, Solary, Eric, André, Fabrice, Pène, Frédéric, Ackerman, Félix, Mouthon, Luc, Zitvogel, Laurence, Marabelle, Aurélien, Michot, Jean-Marie, Fontenay, Michaela, Kroemer, Guido
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 11.03.2021
Springer Nature B.V
Nature Publishing Group
Subjects
101/47
101/58
631/92/320
692/699/255/2514
Anthranilic acid
Antibodies
Antibodies, Monoclonal, Humanized - administration & dosage
Biochemistry
Biomarkers - blood
Biomedical and Life Sciences
Cancer
Cell Biology
Cell Culture
Coronaviruses
COVID-19
COVID-19 - blood
COVID-19 - diagnosis
COVID-19 Drug Treatment
Disease
Female
Humans
Immunology
Intensive care
Interleukin 10
Life Sciences
Lipid metabolism
Male
Metabolites
Metabolome
Metabolomics
Microbiology and Parasitology
Monoclonal antibodies
Pneumonitis
Polyamines
Prognosis
SARS-CoV-2 - metabolism
Tryptophan 2,3-dioxygenase
Online AccessGet full text

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Abstract The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report alterations in the plasma metabolome reflecting the clinical presentation of COVID-19 patients with mild (ambulatory) diseases, moderate disease (radiologically confirmed pneumonitis, hospitalization and oxygen therapy), and critical disease (in intensive care). This analysis revealed major disease- and stage-associated shifts in the metabolome, meaning that at least 77 metabolites including amino acids, lipids, polyamines and sugars, as well as their derivatives, were altered in critical COVID-19 patient’s plasma as compared to mild COVID-19 patients. Among a uniformly moderate cohort of patients who received tocilizumab, only 10 metabolites were different among individuals with a favorable evolution as compared to those who required transfer into the intensive care unit. The elevation of one single metabolite, anthranilic acid, had a poor prognostic value, correlating with the maintenance of high interleukin-10 and -18 levels. Given that products of the kynurenine pathway including anthranilic acid have immunosuppressive properties, we speculate on the therapeutic utility to inhibit the rate-limiting enzymes of this pathway including indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase.
AbstractList The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report alterations in the plasma metabolome reflecting the clinical presentation of COVID-19 patients with mild (ambulatory) diseases, moderate disease (radiologically confirmed pneumonitis, hospitalization and oxygen therapy), and critical disease (in intensive care). This analysis revealed major disease- and stage-associated shifts in the metabolome, meaning that at least 77 metabolites including amino acids, lipids, polyamines and sugars, as well as their derivatives, were altered in critical COVID-19 patient’s plasma as compared to mild COVID-19 patients. Among a uniformly moderate cohort of patients who received tocilizumab, only 10 metabolites were different among individuals with a favorable evolution as compared to those who required transfer into the intensive care unit. The elevation of one single metabolite, anthranilic acid, had a poor prognostic value, correlating with the maintenance of high interleukin-10 and -18 levels. Given that products of the kynurenine pathway including anthranilic acid have immunosuppressive properties, we speculate on the therapeutic utility to inhibit the rate-limiting enzymes of this pathway including indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase.
Abstract The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report alterations in the plasma metabolome reflecting the clinical presentation of COVID-19 patients with mild (ambulatory) diseases, moderate disease (radiologically confirmed pneumonitis, hospitalization and oxygen therapy), and critical disease (in intensive care). This analysis revealed major disease- and stage-associated shifts in the metabolome, meaning that at least 77 metabolites including amino acids, lipids, polyamines and sugars, as well as their derivatives, were altered in critical COVID-19 patient’s plasma as compared to mild COVID-19 patients. Among a uniformly moderate cohort of patients who received tocilizumab, only 10 metabolites were different among individuals with a favorable evolution as compared to those who required transfer into the intensive care unit. The elevation of one single metabolite, anthranilic acid, had a poor prognostic value, correlating with the maintenance of high interleukin-10 and -18 levels. Given that products of the kynurenine pathway including anthranilic acid have immunosuppressive properties, we speculate on the therapeutic utility to inhibit the rate-limiting enzymes of this pathway including indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase.
The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report alterations in the plasma metabolome reflecting the clinical presentation of COVID-19 patients with mild (ambulatory) diseases, moderate disease (radiologically confirmed pneumonitis, hospitalization and oxygen therapy), and critical disease (in intensive care). This analysis revealed major disease- and stage-associated shifts in the metabolome, meaning that at least 77 metabolites including amino acids, lipids, polyamines and sugars, as well as their derivatives, were altered in critical COVID-19 patient's plasma as compared to mild COVID-19 patients. Among a uniformly moderate cohort of patients who received tocilizumab, only 10 metabolites were different among individuals with a favorable evolution as compared to those who required transfer into the intensive care unit. The elevation of one single metabolite, anthranilic acid, had a poor prognostic value, correlating with the maintenance of high interleukin-10 and -18 levels. Given that products of the kynurenine pathway including anthranilic acid have immunosuppressive properties, we speculate on the therapeutic utility to inhibit the rate-limiting enzymes of this pathway including indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase.The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report alterations in the plasma metabolome reflecting the clinical presentation of COVID-19 patients with mild (ambulatory) diseases, moderate disease (radiologically confirmed pneumonitis, hospitalization and oxygen therapy), and critical disease (in intensive care). This analysis revealed major disease- and stage-associated shifts in the metabolome, meaning that at least 77 metabolites including amino acids, lipids, polyamines and sugars, as well as their derivatives, were altered in critical COVID-19 patient's plasma as compared to mild COVID-19 patients. Among a uniformly moderate cohort of patients who received tocilizumab, only 10 metabolites were different among individuals with a favorable evolution as compared to those who required transfer into the intensive care unit. The elevation of one single metabolite, anthranilic acid, had a poor prognostic value, correlating with the maintenance of high interleukin-10 and -18 levels. Given that products of the kynurenine pathway including anthranilic acid have immunosuppressive properties, we speculate on the therapeutic utility to inhibit the rate-limiting enzymes of this pathway including indoleamine 2,3-dioxygenase and tryptophan 2,3-dioxygenase.
ArticleNumber 258
Author Duchemin, Jérôme
Jourdi, Georges
Goubet, Anne-Gaëlle
Zitvogel, Laurence
Levavasseur, Françoise
Roumier, Mathilde
Mouthon, Luc
Bredel, Delphine
Rozenberg, Flore
Griscelli, Frank
Mouraud, Séverine
Pommeret, Fanny
Stoclin, Annabelle
Baciarello, Giulia
Nirmalathasan, Nitharsshini
Fahrner, Jean-Eudes
Kroemer, Guido
Derosa, Lisa
Albigès, Laurence
Dubuisson, Agathe
Soria, Jean-Charles
Pène, Frédéric
Marabelle, Aurélien
Rohmer, Julien
Willekens, Christophe
Sauvat, Allan
Cantin, Delphine
Colomba, Emeline
Vasse, Marc
Solary, Eric
André, Fabrice
Barlesi, Fabrice
Danlos, François-Xavier
Grajeda-Iglesias, Claudia
Ackerman, Félix
Durand, Sylvère
Fontenay, Michaela
Pradon, Caroline
Ellouze, Syrine
Michot, Jean-Marie
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/33707411$$D View this record in MEDLINE/PubMed
https://hal.science/hal-03682045$$DView record in HAL
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– reference: 38355585 - Cell Death Dis. 2024 Feb 14;15(2):142
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Snippet The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report alterations in...
Abstract The circulating metabolome provides a snapshot of the physiological state of the organism responding to pathogenic challenges. Here we report...
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SubjectTerms 101/47
101/58
631/92/320
692/699/255/2514
Anthranilic acid
Antibodies
Antibodies, Monoclonal, Humanized - administration & dosage
Biochemistry
Biomarkers - blood
Biomedical and Life Sciences
Cancer
Cell Biology
Cell Culture
Coronaviruses
COVID-19
COVID-19 - blood
COVID-19 - diagnosis
COVID-19 Drug Treatment
Disease
Female
Humans
Immunology
Intensive care
Interleukin 10
Life Sciences
Lipid metabolism
Male
Metabolites
Metabolome
Metabolomics
Microbiology and Parasitology
Monoclonal antibodies
Pneumonitis
Polyamines
Prognosis
SARS-CoV-2 - metabolism
Tryptophan 2,3-dioxygenase
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Title Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers
URI https://link.springer.com/article/10.1038/s41419-021-03540-y
https://www.ncbi.nlm.nih.gov/pubmed/33707411
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Volume 12
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