1. Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers
- Author
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Giulia Baciarello, Guido Kroemer, Fanny Pommeret, Allan Sauvat, Eric Solary, Delphine Bredel, Nitharsshini Nirmalathasan, Agathe Dubuisson, Lisa Derosa, Annabelle Stoclin, Frank Griscelli, Mathilde Roumier, Fabrice Andre, Jean-Marie Michot, Frédéric Pène, Claudia Grajeda-Iglesias, Jean-Charles Soria, François-Xavier Danlos, Fabrice Barlesi, Jérôme Duchemin, Flore Rozenberg, Caroline Pradon, Françoise Levavasseur, Anne-Gaëlle Goubet, Julien Rohmer, Luc Mouthon, Laurence Zitvogel, Laurence Albiges, Severine Mouraud, Jean-Eudes Fahrner, Christophe Willekens, Sylvère Durand, Emeline Colomba, Aurélien Marabelle, Félix Ackerman, Syrine Ellouze, Michaela Fontenay, Georges Jourdi, Marc Vasse, Delphine Cantin, Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Métabolisme, Cancer et Immunité (CRC - UMR_S 1138), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), Hôpital Foch [Suresnes], Oncologie gynécologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre de Référence National des Syndromes Hyperéosinophiliques (CEREO), Département de cancérologie de l'enfant et de l'adolescent [Gustave Roussy], Hémostase, Inflammation, Thrombose (HITH - U1176 Inserm - CHU Bicêtre), Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Université Paris-Saclay, Université Paris-Saclay, Département de biologie et pathologie médicales [Gustave Roussy], Département de soins aigus [Gustave Roussy] (DSA), Direction de la recherche [Gustave Roussy], ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018), and European Project: 825410,ONCOBIOME
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Male ,Cancer Research ,Kynurenine pathway ,Metabolite ,[SDV]Life Sciences [q-bio] ,Immunology ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,Disease ,Pharmacology ,Antibodies, Monoclonal, Humanized ,Article ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Metabolomics ,Tocilizumab ,Intensive care ,medicine ,Metabolome ,Humans ,lcsh:QH573-671 ,Pneumonitis ,SARS-CoV-2 ,business.industry ,lcsh:Cytology ,COVID-19 ,Cell Biology ,Prognosis ,medicine.disease ,COVID-19 Drug Treatment ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,chemistry ,Viral infection ,Female ,business ,Biomarkers - 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.
- Published
- 2021