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Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers.
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.
  • Danlos FX; INSERM U1015, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Grajeda-Iglesias C; Université Paris Saclay, Faculté de Médecine, 94270, Le Kremlin-Bicêtre, France.
  • Durand S; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Sauvat A; INSERM U1138, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Roumier M; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Cantin D; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Colomba E; Service de Médecine Interne, Hôpital Foch, 92150, Suresnes, France.
  • Rohmer J; Service d'Accueil des Urgences, AP-HP, Hôpital Hôtel-Dieu, 75004, Paris, France.
  • Pommeret F; Département d'Oncologie Médicale, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Baciarello G; Service de Médecine Interne, Hôpital Foch, 92150, Suresnes, France.
  • Willekens C; Département d'Oncologie Médicale, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Vasse M; Département d'Oncologie Médicale, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Griscelli F; Département d'Hématologie, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Fahrner JE; Service de biologie clinique, Hôpital Foch, 92150, Suresnes, France.
  • Goubet AG; Service de virologie, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Dubuisson A; INSERM U1015, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Derosa L; Université Paris Saclay, Faculté de Médecine, 94270, Le Kremlin-Bicêtre, France.
  • Nirmalathasan N; INSERM U1015, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Bredel D; Université Paris Saclay, Faculté de Médecine, 94270, Le Kremlin-Bicêtre, France.
  • Mouraud S; INSERM U1015, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Pradon C; Université Paris Saclay, Faculté de Médecine, 94270, Le Kremlin-Bicêtre, France.
  • Stoclin A; INSERM U1015, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Rozenberg F; Département d'Oncologie Médicale, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Duchemin J; Centre d'Investigation Clinique - Biothérapie, INSERM CICBT1428, 94800, Villejuif, France.
  • Jourdi G; Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Ellouze S; INSERM U1015, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Levavasseur F; INSERM U1015, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Albigès L; Département de Biologie Médicale, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Soria JC; Département de Réanimation, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Barlesi F; Service de Virologie, AP-HP. Centre-Université de Paris, Hôpital Cochin, Paris, France.
  • Solary E; Service d'Hématologie Biologique, AP-HP, Centre-Université de Paris, Hôpital Cochin, 75014, Paris, France.
  • André F; Service d'Hématologie Biologique, AP-HP, Centre-Université de Paris, Hôpital Cochin, 75014, Paris, France.
  • Pène F; Université de Paris, Innovative Therapies in Haemostasis, INSERM 1140, F-75006, Paris, France.
  • Ackerman F; Service d'Hématologie Biologique, AP-HP, Centre-Université de Paris, Hôpital Cochin, 75014, Paris, France.
  • Mouthon L; Université de Paris, Institut Cochin, CNRS UMR8104, INSERM U1016, 75006, Paris, France.
  • Zitvogel L; Département d'Oncologie Médicale, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Marabelle A; Gustave Roussy, Paris-Saclay University, Paris, France.
  • Michot JM; Département d'Oncologie Médicale, Gustave Roussy Cancer Campus, 94800, Villejuif, France.
  • Fontenay M; Aix Marseille University, CNRS, INSERM, CRCM, Marseille, France.
  • Kroemer G; Université Paris Saclay, Faculté de Médecine, 94270, Le Kremlin-Bicêtre, France.
Cell Death Dis ; 12(3): 258, 2021 03 11.
Article in English | MEDLINE | ID: covidwho-1132059
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Metabolome / SARS-CoV-2 / COVID-19 Type of study: Cohort study / Diagnostic study / Observational study / Prognostic study Limits: Female / Humans / Male Language: English Journal: Cell Death Dis Year: 2021 Document Type: Article Affiliation country: S41419-021-03540-y

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Metabolome / SARS-CoV-2 / COVID-19 Type of study: Cohort study / Diagnostic study / Observational study / Prognostic study Limits: Female / Humans / Male Language: English Journal: Cell Death Dis Year: 2021 Document Type: Article Affiliation country: S41419-021-03540-y