COVID-19: Multi-Omics Approach to Identify Molecular Mechanisms Responsible for Risk and Resilience to Adverse Outcomes

COVID-19:多组学方法来识别导致风险和不良结果恢复能力的分子机制

基本信息

  • 批准号:
    10154323
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-04-01 至 2023-03-31
  • 项目状态:
    已结题

项目摘要

Objective: Emerging data from the COVID-19 pandemic indicate that men and African Americans have higher mortality, and cardiometabolic risk factors, including obesity, diabetes, and hypertension, cluster in patients who develop adverse outcomes to SARS-CoV-2 infection. The Veteran population is particularly vulnerable to COVID-19 because of the very high prevalence of cardiometabolic risk factors. However, not all Veterans with COVID-19 experience severe disease, and there is an urgent need to identify novel molecular pathways underlying risk and resilience to COVID-19. Previous work and preliminary studies from our team have demonstrated that targeted proteomics, metabolomics, and miRNA-omics can identify novel biomarkers and molecular pathways associated with cardiovascular health and disease. In this project, we will use a multi-omics to elucidate novel biomarkers and pathways associated with risk and resilience to severe COVID-19. Research Plan: In Aim 1, we will compare expression of pathway-specific biomarkers in hospitalized patients with severe COVID-19 with expression of these biomarkers in patients who do not develop severe COVID-19. Pathway-specific biomarkers reflecting activation of the renin-angiotensin-aldosterone system, systemic inflammation, oxidative stress, immune activation, thrombogenesis, and myocardial injury and stretch will be assessed. The primary endpoints for severe disease will be pathologic elevation of IL-6 levels or troponin I levels. Secondary endpoints will be requirement for mechanical ventilation, congestive heart failure, change in SOFA score, and death. In Aim 2, we will assess the extracellular miRNA and metabolomic profiles of the same two groups of hospitalized COVID-19 patients and determine miRNAs and metabolites differentially expressed between the two groups. Subsequently, we will examine connectivity between miRNA-metabolome networks and clinical endpoints in COVID-19 patients by performing an integrative analysis of differentially expressed miRNAs and metabolites, which will identify metabolic pathways associated with severe infection. Methods: The proposed studies will analyze de-identified blood samples and clinical data from COVID-19 patients hospitalized at the Atlanta VAMC and Emory University Hospital. The samples will be obtained from a bio repository that is currently banking residual plasma and serum from routine laboratory testing of COVID-19 patients. In Aim 1, we will measure levels of aminothiol (oxidative stress), suPAR (thrombogenesis/immune dysregulation), hsCRP (inflammation), hsTnI (myocardial injury), BNP (myocardial stretch), D-dimers (thrombogenesis), angiotensin II, angiotensin-(1-7) and plasma renin activity. Logistic regression modeling will be performed to identify biomarkers predictive of clinical endpoints. In Aim 2, we will use next generation sequencing, RT-qPCR, and high-throughput metabolomics profiling to assess expression of extracellular miRNAs and metabolites. A metabolome wide association study (MWAS) and ensemble feature selection (EFS) will be used to identify robust biomarkers and develop predictive models for severe COVID-19. Data from EFS analysis will input to the program xMWAS, which will determine connectivity between miRNA-metabolome networks and clinical outcomes. Clinical Relevance: Veterans with cardiovascular conditions are at higher risk for SARS-CoV-2 infection and severe disease progression. Our team has the infrastructure and methods in place to conduct in-depth, multi- omics studies to address predictors of adverse outcomes in Veterans with COVID-19 and identify epigenetic and cardiometabolic pathways that determine susceptibility to adverse outcomes. Furthermore, because 50% of the Veteran population at the Atlanta VA Medical Center Veteran is African American, we are in a unique position to address the role of race in susceptibility to severe COVID-19. Discovery of novel biomarkers and pathways associated with severe COVID-19 has broad implications for screening, therapeutics, and implementation of earlier personalized interventional strategies for attenuating adverse outcomes.
目的:来自COVID-19大流行的新数据表明,男性和非裔美国人的死亡率更高

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

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CHARLES D SEARLES其他文献

CHARLES D SEARLES的其他文献

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{{ truncateString('CHARLES D SEARLES', 18)}}的其他基金

COVID-19: Multi-Omics Approach to Identify Molecular Mechanisms Responsible for Risk and Resilience to Adverse Outcomes
COVID-19:多组学方法来识别导致风险和不良结果恢复能力的分子机制
  • 批准号:
    10382290
  • 财政年份:
    2021
  • 资助金额:
    --
  • 项目类别:
The Production of Microparticles During RBC Storage and Their Impact on Endothelial Phenotype In-vitro and In-vivo
红细胞储存过程中微粒的产生及其对体内外内皮表型的影响
  • 批准号:
    9167980
  • 财政年份:
    2016
  • 资助金额:
    --
  • 项目类别:
The Production of Microparticles During RBC Storage and Their Impact on Endothelial Phenotype In-vitro and In-vivo
红细胞储存过程中微粒的产生及其对体内外内皮表型的影响
  • 批准号:
    9323550
  • 财政年份:
    2016
  • 资助金额:
    --
  • 项目类别:
Modulation of Endothelial Cell Function by the Shear Stress-Responsive miR-155
剪切应力响应性 miR-155 对内皮细胞功能的调节
  • 批准号:
    8162633
  • 财政年份:
    2011
  • 资助金额:
    --
  • 项目类别:
Modulation of Endothelial Cell Function by the Shear Stress-Responsive miR-155
剪切应力响应性 miR-155 对内皮细胞功能的调节
  • 批准号:
    8668133
  • 财政年份:
    2011
  • 资助金额:
    --
  • 项目类别:
Modulation of Endothelial Cell Function by the Shear Stress-Responsive miR-155
剪切应力响应性 miR-155 对内皮细胞功能的调节
  • 批准号:
    8309223
  • 财政年份:
    2011
  • 资助金额:
    --
  • 项目类别:
Modulation of Endothelial Cell Function by the Shear Stress-Responsive miR-155
剪切应力响应性 miR-155 对内皮细胞功能的调节
  • 批准号:
    8465266
  • 财政年份:
    2011
  • 资助金额:
    --
  • 项目类别:
The Impact of miR-21 Expression on Endothelial Cell Apoptosis and Inflammation
miR-21表达对内皮细胞凋亡和炎症的影响
  • 批准号:
    8391582
  • 财政年份:
    2010
  • 资助金额:
    --
  • 项目类别:
The Impact of miR-21 Expression on Endothelial Cell Apoptosis and Inflammation
miR-21表达对内皮细胞凋亡和炎症的影响
  • 批准号:
    8196330
  • 财政年份:
    2010
  • 资助金额:
    --
  • 项目类别:
The Impact of miR-21 Expression on Endothelial Cell Apoptosis and Inflammation
miR-21表达对内皮细胞凋亡和炎症的影响
  • 批准号:
    7931520
  • 财政年份:
    2010
  • 资助金额:
    --
  • 项目类别:

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GODDESS (Gathering Online for Dialogue and Discussion to Enhance Social Support): Engaging young African American women in a virtual group app to address alcohol misuse, sexual risk, and PrEP in NC
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解决疫苗犹豫问题并提高南方非裔美国年轻人对 COVID-19 疫苗接种率的多维数字方法
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    --
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A multidimensional Digital Approach to Address Vaccine Hesitancy and Increase COVID-19 Vaccine Uptake among African American Young Adults in the South
解决疫苗犹豫问题并提高南方非裔美国年轻人对 COVID-19 疫苗接种率的多维数字方法
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减少非裔美国男性的高血压:解决健康差异的移动压力管理干预措施
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减少非裔美国男性的高血压:解决健康差异的移动压力管理干预措施
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建立一个多学科研究计划来解决高血压差异:探索非裔美国高血压女性自我管理干预的神经认知机制
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