Nucleotide, Phospholipid, and Kynurenine Metabolites Are Robustly Associated with COVID-19 Severity and Time of Plasma Sample Collection in a Prospective Cohort Study.
Nucleotide, Phospholipid, and Kynurenine Metabolites Are Robustly Associated with COVID-19 Severity and Time of Plasma Sample Collection in a Prospective Cohort Study.
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在一项前瞻性队列研究中，核苷酸，磷脂和kynurenine代谢物与CoVID-19的严重程度和等离子体样品收集的时间牢固相关。
DOI：
10.3390/ijms25010346
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发表时间：
2023-12-26
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
了解人类研究中疾病严重程度和进展的分子基础对于制定针对严重COVID-19的代谢相关预防策略是必要的。使个体易患严重疾病的代谢和代谢途径还不清楚。在这项研究中，我们在纵向EMR和组学COVID-19队列的>550名患者中生成了全面的血浆代谢组学特征。在COVID-19诊断之前（n = 441），期间（n = 86）和之后（n = 82）收集了样本，代表555名不同的患者，其中大多数具有单个时间点。根据人口统计学、风险因素和合并症调整的回归模型用于确定与COVID-19严重程度的易感性和/或持续影响相关的代谢物，以及在病程中短暂/持续的代谢物变化。鞘脂/磷脂与严重程度呈负相关，并在疾病发生后持续升高，而修饰的核苷酸与严重程度呈正相关，并在疾病发生后持续降低。分别与COVID-19严重程度呈正相关和负相关的胞苷和尿苷代谢物急性升高，反映了嘧啶代谢在活动性COVID-19中的特别重要性。这是第一个使用COVID-19血浆样本在疾病之前，期间和/或之后进行的大型代谢组学研究。我们的结果为确定严重COVID-19的推定生物标志物和预防策略奠定了基础。
Understanding the molecular underpinnings of disease severity and progression in human studies is necessary to develop metabolism-related preventative strategies for severe COVID-19. Metabolites and metabolic pathways that predispose individuals to severe disease are not well understood. In this study, we generated comprehensive plasma metabolomic profiles in >550 patients from the Longitudinal EMR and Omics COVID-19 Cohort. Samples were collected before (n = 441), during (n = 86), and after (n = 82) COVID-19 diagnosis, representing 555 distinct patients, most of which had single timepoints. Regression models adjusted for demographics, risk factors, and comorbidities, were used to determine metabolites associated with predisposition to and/or persistent effects of COVID-19 severity, and metabolite changes that were transient/lingering over the disease course. Sphingolipids/phospholipids were negatively associated with severity and exhibited lingering elevations after disease, while modified nucleotides were positively associated with severity and had lingering decreases after disease. Cytidine and uridine metabolites, which were positively and negatively associated with COVID-19 severity, respectively, were acutely elevated, reflecting the particular importance of pyrimidine metabolism in active COVID-19. This is the first large metabolomics study using COVID-19 plasma samples before, during, and/or after disease. Our results lay the groundwork for identifying putative biomarkers and preventive strategies for severe COVID-19.
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影响因子：
7.4
作者：
Delafiori J;Navarro LC;Siciliano RF;de Melo GC;Busanello ENB;Nicolau JC;Sales GM;de Oliveira AN;Val FFA;de Oliveira DN;Eguti A;Dos Santos LA;Dalçóquio TF;Bertolin AJ;Abreu-Netto RL;Salsoso R;Baía-da-Silva D;Marcondes-Braga FG;Sampaio VS;Judice CC;Costa FTM;Durán N;Perroud MW;Sabino EC;Lacerda MVG;Reis LO;Fávaro WJ;Monteiro WM;Rocha AR;Catharino RR
通讯作者：
Catharino RR
DOI：
10.1016/j.metabol.2022.155197
发表时间：
2022-06
期刊：
Metabolism: clinical and experimental
影响因子：
--
作者：
Castañé H;Iftimie S;Baiges-Gaya G;Rodríguez-Tomàs E;Jiménez-Franco A;López-Azcona AF;Garrido P;Castro A;Camps J;Joven J
通讯作者：
Joven J
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
9
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
通讯作者：
Kroemer G
影响因子：
5.6
作者：
Caterino M;Costanzo M;Fedele R;Cevenini A;Gelzo M;Di Minno A;Andolfo I;Capasso M;Russo R;Annunziata A;Calabrese C;Fiorentino G;D'Abbraccio M;Dell'Isola C;Fusco FM;Parrella R;Fabbrocini G;Gentile I;Castaldo G;Ruoppolo M
通讯作者：
Ruoppolo M