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

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Danlos, François-Xavier | Grajeda-Iglesias, Claudia | Durand, Sylvère | Sauvat, Allan | Roumier, Mathilde | Cantin, Delphine | Colomba, Emeline | Rohmer, Julien | Pommeret, Fanny | Baciarello, Giulia | Willekens, Christophe | Vasse, Marc | Griscelli, Frank | Fahrner, Jean-Eudes | Goubet, Anne-Gaëlle | Dubuisson, Agathe | Derosa, Lisa | Nirmalathasan, Nitharsshini | Bredel, Delphine | Mouraud, Séverine | Pradon, Caroline | Stoclin, Annabelle | Rozenberg, Flore | Duchemin, Jérôme | Jourdi, Georges | Ellouze, Syrine | Levavasseur, Françoise | Albigès, Laurence | Soria, Jean-Charles | Barlesi, Fabrice | Solary, Éric | André, Fabrice | Pène, Frédéric | Ackerman, Félix | Mouthon, Luc | Zitvogel, Laurence | Marabelle, Aurélien | Michot, Jean-Marie | Fontenay, Michaela | Kroemer, Guido

Edité par CCSD ; Nature Publishing Group -

International audience. 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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