Inflammatory and Metabolic Biomarkers in Cardiovascular Complications with SARS-CoV-2

SARS-CoV-2 心血管并发症中的炎症和代谢生物标志物

• 批准号: 10303644
• 负责人: Svati H. Shah
• 金额: $ 25.59万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-10 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10303644
• 关键词: 2019-nCoV; ACE2; Angiotensins; Biological; Biological Markers; Biology; Blood; Blood specimen; COVID-19; COVID-19 pandemic; COVID-19 patient; Cardiovascular Diseases; Cardiovascular system; Clinical; Complement; Complex; Coronavirus; Data; Development; Diagnostic; Disease; Disease Outcome; Disease Progression; Epidemiology; Evaluation; Genes; Genetic; Genetic Markers; Goals; Heterogeneity; Impairment; Individual; Infection; Inflammation; Inflammatory; Inpatients; Lung; Machine Learning; Measures; Medical center; Metabolic; Metabolic Pathway; Metabolism; Molecular; Monitor; North Carolina; Organ; Outcome; Outpatients; Output; Pathway interactions; Patients; Population Heterogeneity; Predisposition; Proteins; Proteomics; Risk; Risk Factors; Role; SARS-CoV-2 infection; Severe Acute Respiratory Syndrome; Severities; Specimen; Technology; Universities; Work; biobank; cardiovascular disorder risk; clinical biomarkers; clinical predictors; cohort; cytokine; endoplasmic reticulum stress; fatty acid oxidation; high risk; improved; metabolomics; mortality; novel; novel therapeutic intervention; prevent; progression marker; racial difference; racial disparity; secondary outcome; thrombotic

One of the most poorly understood yet clinically important aspects of the novel COVID-19 SARS CoV2 coronavirus is the marked heterogeneity that it displays with infection severity and with development of end organ complications and mortality. SARS CoV-2 infection has a complex epidemiologic interplay with cardiovascular (CVD) and highlights this complex heterogeneity. The biology underlying this heterogeneity in CVD outcomes is poorly understood and concomitantly, clinically useful biomarkers do not currently exist to identify the highest risk patients in need of the most intense monitoring. Thus, we propose to use integrated omics and EHR data in a diverse multi-center North Carolina cohort with existing biological specimens to determine the role of inflammation, metabolism and novel molecular mechanisms, and identify biomarkers of CVD outcomes in patients with COVID-19. We propose to (1) Determine the clinical predictors of infection severity in a diverse population of individuals with CVD risk factors and SARS-CoV2 infection including evaluation of racial differences; (2) Determine the role of inflammatory, SARS-CoV-2 related, and other candidate proteins as biomarkers of infection severity and CVD outcomes in patients with SARS CoV-2 infection; and (3) Evaluate metabolic pathways in SARS Co-V-2 infection severity and CVD outcomes. The proposal has high potential for dissecting the molecular mechanisms of the heterogeneity between CVD and SARS CoV-2 outcomes. Importantly, it has great short-term potential for clinically important results that will lead to earlier and better identification of high-risk patients for more intensive monitoring; novel therapeutic interventions to prevent end organ complications and mortality; and diagnostic and disease-progression biomarkers.

新新冠肺炎SARS最鲜为人知但临床上最重要的方面之一 CoV2冠状病毒是一种显著的异质性，它随着感染的严重性和 终末器官并发症和死亡率的发展。SARS冠状病毒-2感染具有复杂性 流行病学与心血管疾病(CVD)的相互作用，并突出了这种复杂的异质性。 心血管疾病结局的这种异质性背后的生物学基础尚不清楚， 随之而来的是，目前还不存在临床上有用的生物标记物来识别最高风险 需要最严密监护的病人。因此，我们建议使用集成组学和 北卡罗来纳州一个多样化的多中心队列中的EHR数据与现有的生物样本 确定炎症、代谢和新的分子机制的作用，并确定 新冠肺炎患者心血管疾病预后的生物标志物。我们建议(1)确定 心血管疾病风险人群不同人群感染严重程度的临床预测因素 因素与SARS-CoV2感染包括种族差异的评估；(2)决定 炎症、SARS-CoV-2相关蛋白和其他候选蛋白作为SARS-CoV-2生物标志物的作用 SARS CoV-2感染患者的感染严重程度和心血管结局；以及(3)评估 SARS Co-V-2感染严重程度和心血管疾病结局中的代谢途径。这项提案已经 对CVD和CVD之间异质性的分子机制的高潜力剖析 SARS CoV-2的转归。重要的是，它在临床上具有很大的短期潜力。 这一结果将导致更早和更好地识别高危患者进行更密集的治疗 监测；预防终末器官并发症和死亡的新的治疗干预措施； 以及诊断和疾病进展的生物标志物。