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: 10426342
• 负责人: Svati H. Shah
• 金额: $ 20.04万
• 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 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10426342
• 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; 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.

新型Covid-19 SARS的最知名度尚不理解但临床上重要的方面之一 COV2冠状病毒是其具有感染严重程度的明显异质性 最终器官并发症和死亡率的发展。 SARS COV-2感染具有复杂的 与心血管（CVD）的流行病学相互作用，突出显示了这种复杂的异质性。 CVD结果中这种异质性的基础生物学知识很少 同时，目前尚不存在临床上有用的生物标志物来识别最高风险 需要最激烈监测的患者。因此，我们建议使用集成的OMIC和 EHR数据中有多种多样的北卡罗来纳州队列，现有的生物标本 确定炎症，新陈代谢和新型分子机制的作用，并确定 COVID-19患者CVD结局的生物标志物。我们建议（1）确定 CVD风险的个体种群中感染严重程度的临床预测因子 因素和SARS-COV2感染，包括评估种族差异； （2）确定 炎症性，SARS-COV-2与其他候选蛋白作为生物标志物的作用 SARS COV-2感染患者的感染严重程度和CVD结局； （3）评估 SARS CO-V-2感染严重程度和CVD结果中的代谢途径。提案有 剖析CVD和CVD之间异质性的分子机制的高潜力 SARS COV-2结果。重要的是，它具有临床上重要的短期潜力 结果将导致更早的高风险患者较早，更强化的结果 监视；新的治疗干预措施，以防止最终器官并发症和死亡率； 以及诊断和疾病产生生物标志物。