Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers
François‐Xavier Danlos, Claudia Grajeda‐Iglesias, Sylvère Durand, Allan Sauvat, Mathilde Roumier, Delphine Cantin, Émeline Colomba, Julien Rohmer, Fanny Pommeret, Giulia Baciarello, Christophe Willekens, Marc Vasse, Frank Griscelli, Jean‐Eudes Fahrner, Anne‐Gaëlle Goubet, Agathe Dubuisson, Lisa Derosa, Nitharsshini Nirmalathasan, Delphine Bredel, Séverine Mouraud, Caroline Pradon, Annabelle Stoclin, Flore Rozenberg, Jérôme Duchemin, Georges Jourdi, Syrine Ellouze, Françoise Levavasseur, Laurence Albigès, Jean‐Charles Soria, Fabrice Barlési, Éric Solary, Fabrice André, Frédéric Pène, Félix Ackerman, Luc Mouthon, Laurence Zitvogel, Aurélien Marabelle, Jean‐Marie Michot, Michaëla Fontenay, Guido Kroemer
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.