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

被引:127
作者
Danlos, Francois-Xavier [1 ,2 ]
Grajeda-Iglesias, Claudia [3 ,4 ]
Durand, Sylvere [3 ]
Sauvat, Allan [3 ]
Roumier, Mathilde [5 ]
Cantin, Delphine [6 ]
Colomba, Emeline [7 ]
Rohmer, Julien [5 ]
Pommeret, Fanny [7 ]
Baciarello, Giulia [7 ]
Willekens, Christophe [8 ]
Vasse, Marc [9 ]
Griscelli, Frank [10 ]
Fahrner, Jean-Eudes [1 ,2 ]
Goubet, Anne-Gaelle [1 ,2 ]
Dubuisson, Agathe [1 ,2 ]
Derosa, Lisa [1 ,7 ,11 ]
Nirmalathasan, Nitharsshini [3 ]
Bredel, Delphine [1 ]
Mouraud, Severine [1 ]
Pradon, Caroline [12 ]
Stoclin, Annabelle [13 ]
Rozenberg, Flore [14 ]
Duchemin, Jerome [15 ]
Jourdi, Georges [16 ]
Ellouze, Syrine
Levavasseur, Francoise [17 ]
Albiges, Laurence [7 ]
Soria, Jean-Charles [18 ]
Barlesi, Fabrice [7 ]
Solary, Eric [2 ,8 ,20 ]
Andre, Fabrice [2 ,7 ,19 ,21 ]
Pene, Frederic [22 ]
Ackerman, Felix [5 ]
Mouthon, Luc [23 ]
Zitvogel, Laurence [1 ,2 ,11 ]
Marabelle, Aurelien [1 ,2 ,11 ,24 ]
Michot, Jean-Marie [8 ,24 ]
Fontenay, Michaela
Kroemer, Guido [3 ,25 ,26 ,27 ,28 ]
机构
[1] INSERM, U1015, Gustave Roussy Canc Campus, F-94800 Villejuif, France
[2] Univ Paris Saclay, Fac Med, F-94270 Le Kremlin Bicetre, France
[3] Metabol & Cell Biol Platforms, Gustave Roussy Canc Campus, F-94800 Villejuif, France
[4] INSERM, U1138, Gustave Roussy Canc Campus, F-94800 Villejuif, France
[5] Hop Foch, Serv Med Interne, F-92150 Suresnes, France
[6] Hop Hotel Dieu, AP HP, Serv Accueil Urgences, F-75004 Paris, France
[7] Gustave Roussy Canc Campus, Dept Oncol Med, F-94800 Villejuif, France
[8] Gustave Roussy Canc Campus, Dept Hematol, S-94800 Villejuif, Sweden
[9] Hop Foch, Serv Biol Clin, F-92150 Suresnes, France
[10] Gustave Roussy Canc Campus, Serv Virol, F-94800 Villejuif, France
[11] INSERM CICBT1428, Ctr Invest Clin Biotherapie, F-94800 Villejuif, France
[12] Gustave Roussy Canc Campus, Dept Biol Med, F-94800 Villejuif, France
[13] Gustave Roussy Canc Campus, Dept Reanimat, F-94800 Villejuif, France
[14] Hop Cochin, AP HP, Serv Virol, Ctr Univ Paris, Paris, France
[15] Hop Cochin, AP HP, Serv Hematol Biol, Ctr Univ Paris, F-75014 Paris, France
[16] Univ Paris, Innovat Therapies Haemostasis, INSERM 1140, F-75006 Paris, France
[17] Univ Paris, Inst Cochin, CNRS, UMR8104,INSERM U1016, Paris, France
[18] Univ Paris Saclay, Gustave Roussy, Paris, France
[19] Aix Marseille Univ, CNRS, INSERM, CRCM, Marseille, France
[20] Gustave Roussy Canc Campus, INSERM U1287, F-94800 Villejuif, France
[21] Gustave Roussy Canc Campus, INSERM U981, F-94800 Villejuif, France
[22] Hop Cochin, AP HP, Serv Med Intens & Reanimat, F-75014 Paris, France
[23] Hop Cochin, AP HP, Serv Med Interne, F-75014 Paris, France
[24] Gustave Roussy Canc Campus, Dept Innovat Therapeut & Essais Precoces, F-94800 Villejuif, France
[25] Univ Paris, Sorbonne Univ, Inst Univ France,U1138, INSERM,Ctr Rech Cordeliers,Equipe Labellisee Ligu, Paris, France
[26] Hop Europeen Georges Pompidou, AP HP, Pole Biol, F-75015 Paris, France
[27] Chinese Acad Sci, Suzhou Inst Syst Biol, Suzhou, Peoples R China
[28] Karolinska Univ Hosp, Dept Womens & Childrens Hlth, S-17176 Stockholm, Sweden
关键词
ANTHRANILIC ACID; INHIBITORS; CANCER; IDO;
D O I
10.1038/s41419-021-03540-y
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页数:11
相关论文
共 39 条
[1]   Characterization of indoleamine-2,3-dioxygenase 1, tryptophan-2,3-dioxygenase, and Ido1/Tdo2 knockout mice [J].
Aslamkhan, Amy G. ;
Xu, Qiuwei ;
Loughlin, Amy ;
Vu, Heather ;
Pacchione, Stephen ;
Bhatt, Bhavana ;
Garfinkel, Ivy ;
Styring, Tara Grady ;
LaFranco-Scheuch, Lisa ;
Pearson, Kara ;
Reynolds, Spencer ;
Li, Nianyu ;
Zhou, Heather ;
Miller, J. Richard ;
Solban, Nicolas ;
Bass, Alan ;
Glaab, Warren E. .
TOXICOLOGY AND APPLIED PHARMACOLOGY, 2020, 406
[2]   Severe Covid-19 [J].
Berlin, David A. ;
Gulick, Roy M. ;
Martinez, Fernando J. .
NEW ENGLAND JOURNAL OF MEDICINE, 2020, 383 (25) :2451-2460
[3]  
Cai Yuping, 2020, medRxiv, DOI 10.1101/2020.09.06.20189159
[4]   Regulating T-cell differentiation through the polyamine spermidine [J].
Carriche, Guilhermina M. ;
Almeida, Luis ;
Stuve, Philipp ;
Velasquez, Lis ;
Dhillon-LaBrooy, Ayesha ;
Roy, Urmi ;
Lindenberg, Marc ;
Strowig, Till ;
Plaza-Sirvent, Carlos ;
Schmitz, Ingo ;
Lochner, Matthias ;
Simon, Anna Katharina ;
Sparwasser, Tim .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2021, 147 (01) :335-+
[5]   Serum Proteomics in COVID-19 Patients: Altered Coagulation and Complement Status as a Function of IL-6 Level [J].
D'Alessandro, Angelo ;
Thomas, Tiffany ;
Dzieciatkowska, Monika ;
Hill, Ryan C. ;
Francis, Richard O. ;
Hudson, Krystalyn E. ;
Zimring, James C. ;
Hod, Eldad A. ;
Spitalnik, Steven L. ;
Hansen, Kirk C. .
JOURNAL OF PROTEOME RESEARCH, 2020, 19 (11) :4417-4427
[6]  
Del Valle DM, 2020, NAT MED, V26, P1636, DOI [10.1101/2020.05.28.20115758, 10.1038/s41591-020-1051-9]
[7]   Genomewide Association Study of Severe Covid-19 with Respiratory Failure [J].
Ellinghaus, David ;
Degenhardt, Frauke ;
Bujanda, Luis ;
Buti, Maria ;
Albillos, Agustin ;
Invernizzi, Pietro ;
Fernandez, Javier ;
Prati, Daniele ;
Baselli, Guido ;
Asselta, Rosanna ;
Grimsrud, Marit M. ;
Milani, Chiara ;
Aziz, Fatima ;
Kassens, Jan ;
May, Sandra ;
Wendorff, Mareike ;
Wienbrandt, Lars ;
Uellendahl-Werth, Florian ;
Zheng, Tenghao ;
Yi, Xiaoli ;
de Pablo, Raul ;
Chercoles, Adolfo G. ;
Palom, Adriana ;
Garcia-Fernandez, Alba-Estela ;
Rodriguez-Frias, Francisco ;
Zanella, Alberto ;
Bandera, Alessandra ;
Protti, Alessandro ;
Aghemo, Alessio ;
Lleo, Ana ;
Biondi, Andrea ;
Caballero-Garralda, Andrea ;
Gori, Andrea ;
Tanck, Anja ;
Nolla, Anna Carreras ;
Latiano, Anna ;
Fracanzani, Anna Ludovica ;
Peschuck, Anna ;
Julia, Antonio ;
Pesenti, Antonio ;
Voza, Antonio ;
Jimenez, David ;
Mateos, Beatriz ;
Jimenez, Beatriz Nafria ;
Quereda, Carmen ;
Paccapelo, Cinzia ;
Gassner, Christoph ;
Angelini, Claudio ;
Cea, Cristina ;
Solier, Aurora .
NEW ENGLAND JOURNAL OF MEDICINE, 2020, 383 (16) :1522-1534
[8]  
Garcia-Alvarez F, 2000, Int J Surg Investig, V2, P9
[9]   First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA [J].
Ghinai, Isaac ;
McPherson, Tristan D. ;
Hunter, Jennifer C. ;
Kirking, Hannah L. ;
Christiansen, Demian ;
Joshi, Kiran ;
Rubin, Rachel ;
Morales-Estrada, Shirley ;
Black, Stephanie R. ;
Pacilli, Massimo ;
Fricchione, Marielle J. ;
Chugh, Rashmi K. ;
Walblay, Kelly A. ;
Ahmed, N. Seema ;
Stoecker, William C. ;
Hasan, Nausheen F. ;
Burdsall, Deborah P. ;
Reese, Heather E. ;
Wallace, Megan ;
Wang, Chen ;
Moeller, Darcie ;
Korpics, Jacqueline ;
Novosad, Shannon A. ;
Benowitz, Isaac ;
Jacobs, Max W. ;
Dasari, Vishal S. ;
Patel, Megan T. ;
Kauerauf, Judy ;
Charles, E. Matt ;
Ezike, Ngozi O. ;
Chu, Victoria ;
Midgley, Claire M. ;
Rolfes, Melissa A. ;
Gerber, Susan I. ;
Lu, Xiaoyan ;
Lindstrom, Stephen ;
Verani, Jennifer R. ;
Layden, Jennifer E. .
LANCET, 2020, 395 (10230) :1137-1144
[10]   Interleukin-6 as prognosticator in patients with COVID-19 [J].
Grifoni, Elisa ;
Valoriani, Alice ;
Cei, Francesco ;
Lamanna, Roberta ;
Gelli, Anna Maria Grazia ;
Ciambotti, Benedetta ;
Vannucchi, Vieri ;
Moroni, Federico ;
Pelagatti, Lorenzo ;
Tarquini, Roberto ;
Landini, Giancarlo ;
Vanni, Simone ;
Masotti, Luca .
JOURNAL OF INFECTION, 2020, 81 (03) :466-467