학술논문
Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers
Document Type
article
Author
François-Xavier Danlos; Claudia Grajeda-Iglesias; Sylvère Durand; Allan Sauvat; Mathilde Roumier; Delphine Cantin; Emeline 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 Barlesi; Eric Solary; Fabrice André; Frédéric Pène; Félix Ackerman; Luc Mouthon; Laurence Zitvogel; Aurélien Marabelle; Jean-Marie Michot; Michaela Fontenay; Guido Kroemer
Source
Cell Death and Disease, Vol 12, Iss 3, Pp 1-11 (2021)
Subject
Language
English
ISSN
2041-4889
Abstract
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.