Journal Article

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

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

2021

Overview

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.

• Publisher: Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
• Subject: 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