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

INSERM U1015, Gustave Roussy Cancer Campus, 94800, Villejuif, France. Université Paris Saclay, Faculté de Médecine, 94270, Le Kremlin-Bicêtre, France. Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, 94800, Villejuif, France. INSERM U1138, Gustave Roussy Cancer Campus, 94800, Villejuif, France. Service de Médecine Interne, Hôpital Foch, 92150, Suresnes, France. Service d'Accueil des Urgences, AP-HP, Hôpital Hôtel-Dieu, 75004, Paris, France. Département d'Oncologie Médicale, Gustave Roussy Cancer Campus, 94800, Villejuif, France. Département d'Hématologie, Gustave Roussy Cancer Campus, 94800, Villejuif, France. Service de biologie clinique, Hôpital Foch, 92150, Suresnes, France. Service de virologie, Gustave Roussy Cancer Campus, 94800, Villejuif, France. Centre d'Investigation Clinique - Biothérapie, INSERM CICBT1428, 94800, Villejuif, France. Département de Biologie Médicale, Gustave Roussy Cancer Campus, 94800, Villejuif, France. Département de Réanimation, Gustave Roussy Cancer Campus, 94800, Villejuif, France. Service de Virologie, AP-HP. Centre-Université de Paris, Hôpital Cochin, Paris, France. Service d'Hématologie Biologique, AP-HP, Centre-Université de Paris, Hôpital Cochin, 75014, Paris, France. Université de Paris, Innovative Therapies in Haemostasis, INSERM 1140, F-75006, Paris, France. Université de Paris, Institut Cochin, CNRS UMR8104, INSERM U1016, 75006, Paris, France. Gustave Roussy, Paris-Saclay University, Paris, France. Aix Marseille University, CNRS, INSERM, CRCM, Marseille, France. INSERM U1287, Gustave Roussy Cancer Campus, 94800, Villejuif, France. INSERM U981, Gustave Roussy Cancer Campus, 94800, Villejuif, France. Service de Médecine Intensive et Réanimation, AP-HP, Hôpital Cochin, 75014, Paris, France. Service de Médecine Interne, AP-HP, Hôpital Cochin, 75014, Paris, France. Département d'Innovation Thérapeutique et des Essais Précoces, Gustave Roussy Cancer Campus, 94800, Villejuif, France. Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, 94800, Villejuif, France. kroemer@orange.fr. Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Université de Paris, Sorbonne Université, INSERM U1138, Institut Universitaire de France, Paris, France. kroemer@orange.fr. Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, 75015, Paris, France. kroemer@orange.fr. Suzhou Institute for Systems Biology, Chinese Academy of Sciences, Suzhou, China. kroemer@orange.fr. Department of Women's and Children's Health, Karolinska University Hospital, 17176, Stockholm, Sweden. kroemer@orange.fr.

Cell death & disease. 2021;(3):258
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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.

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MeSH terms : SARS-CoV-2