Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers.
Metabolomic analyses of COVID-19 patients unravel stage-dependent and prognostic biomarkers.
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DOI：
10.1038/s41419-021-03540-y
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发表时间：
2021-03-11
影响因子：
9
通讯作者：
Kroemer G
中科院分区：
文献类型：
--
作者：
Danlos FX;Grajeda-Iglesias C;Durand S;Sauvat A;Roumier M;Cantin D;Colomba E;Rohmer J;Pommeret F;Baciarello G;Willekens C;Vasse M;Griscelli F;Fahrner JE;Goubet AG;Dubuisson A;Derosa L;Nirmalathasan N;Bredel D;Mouraud S;Pradon C;Stoclin A;Rozenberg F;Duchemin J;Jourdi G;Ellouze S;Levavasseur F;Albigès L;Soria JC;Barlesi F;Solary E;André F;Pène F;Ackerman F;Mouthon L;Zitvogel L;Marabelle A;Michot JM;Fontenay M;Kroemer G
循环代谢组提供了生物体响应病原体挑战的生理状态的快照。在这里，我们报告了血浆代谢组的变化，反映了COVID-19患者的临床表现，包括轻度（非卧床）疾病、中度疾病（经放射学证实的肺炎、住院和氧疗）和危重疾病（重症监护）。这项分析揭示了代谢组中与疾病和阶段相关的主要变化，这意味着与轻度COVID-19患者相比，危重COVID-19患者血浆中至少有77种代谢物（包括氨基酸、脂质、多胺和糖及其衍生物）发生了改变。在接受托珠单抗治疗的均匀中度患者队列中，与需要转入重症监护室的患者相比，具有有利进展的个体中仅10种代谢物不同。一个单一的代谢产物，邻氨基苯甲酸的升高，具有不良的预后价值，与维持高白细胞介素-10和-18水平。考虑到犬尿氨酸途径的产物包括邻氨基苯甲酸具有免疫抑制特性，我们推测抑制该途径的限速酶包括吲哚胺2，3-双加氧酶和色氨酸2，3-双加氧酶的治疗效用。
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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影响因子：
82.9
作者：
Del Valle DM;Kim-Schulze S;Huang HH;Beckmann ND;Nirenberg S;Wang B;Lavin Y;Swartz TH;Madduri D;Stock A;Marron TU;Xie H;Patel M;Tuballes K;Van Oekelen O;Rahman A;Kovatch P;Aberg JA;Schadt E;Jagannath S;Mazumdar M;Charney AW;Firpo-Betancourt A;Mendu DR;Jhang J;Reich D;Sigel K;Cordon-Cardo C;Feldmann M;Parekh S;Merad M;Gnjatic S
通讯作者：
Gnjatic S
影响因子：
5
作者：
Rosa, Flavia Troncon;Freitas, Ellen Cristini;Marchini, Julio Sergio
通讯作者：
Marchini, Julio Sergio
DOI：
10.1073/pnas.1113873109
发表时间：
2012-02-14
影响因子：
11.1
作者：
Pilotte, Luc;Larrieu, Pierre;Van den Eynde, Benoit J.
通讯作者：
Van den Eynde, Benoit J.
影响因子：
4.4
作者：
D'Alessandro, Angelo;Thomas, Tiffany;Hansen, Kirk C.
通讯作者：
Hansen, Kirk C.
影响因子：
11.2
作者：
Prendergast GC;Malachowski WP;DuHadaway JB;Muller AJ
通讯作者：
Muller AJ