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

• Published in: Cell death & disease Vol. 12; no. 3; pp. 258 - 11
• Main Authors: 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, Eric, André, Fabrice, Pène, Frédéric, Ackerman, Félix, Mouthon, Luc, Zitvogel, Laurence, Marabelle, Aurélien, Michot, Jean-Marie, Fontenay, Michaela, Kroemer, Guido
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 11.03.2021; Springer Nature B.V; Nature Publishing Group
• Subjects: 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
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-021-03540-y

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.