PDF(Pubmed)
Abstract：
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.
摘要：
在人类研究中了解疾病严重程度和进展的分子基础对于制定与代谢相关的严重COVID-19预防策略是必要的。对个体易患严重疾病的代谢物和代谢途径没有很好的了解。在这项研究中,我们在纵向EMR和OmicsCOVID-19队列中>550例患者中生成了全面的血浆代谢组学谱。之前收集样品（n=441），在(n=86)期间，在(n=82)COVID-19诊断后，代表555个不同的病人，其中大多数有单一的时间点。针对人口统计进行调整的回归模型，危险因素，和合并症，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，和代谢物的变化是短暂的/挥之不去的疾病过程。鞘脂/磷脂与严重程度呈负相关，并在疾病后表现出挥之不去的升高，而修饰的核苷酸与严重程度呈正相关，并且在疾病后持续减少。胞苷和尿苷代谢物，与COVID-19严重程度呈正相关和负相关，分别,急剧升高，反映了嘧啶代谢在活性COVID-19中的特殊重要性。这是首次使用COVID-19血浆样本进行的大型代谢组学研究，during,和/或疾病后。我们的研究结果为确定严重COVID-19的推定生物标志物和预防策略奠定了基础。
