Administrative Core

行政核心

• 批准号: 10165163
• 负责人: Kenneth Mark Coggeshall
• 金额: $ 83.28万
• 依托单位: OKLAHOMA MEDICAL RESEARCH FOUNDATION
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-08 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10165163
• 关键词: 2019-nCoV; Activation Analysis; Acute; Address; Age; American; American Indians; Anthrax disease; Antibodies; Antibody-Dependent Enhancement; Attention; B-Lymphocyte Epitopes; Biological Markers; Biological Response Modifier Therapy; Birds; CD8-Positive T-Lymphocytes; COVID-19; CXCR3 gene; Caring; Cells; Censuses; Cessation of life; Clinic; Clinical; Clonal Expansion; Coronavirus; Diabetes Mellitus; Disease; Disease Outcome; Epitopes; Ethnic group; European; Gender; Genes; Genetic Transcription; Glucose; Goals; HIF1A gene; HLA-DR Antigens; Haplotypes; Health; Healthcare; Heart Diseases; Home environment; Human; Hydroxychloroquine; Hypertension; IL1R1 gene; IL6 gene; Immune response; Immune system; Immunologics; Individual; Infection; Inflammatory; Influenza; Influenza A Virus, H7N9 Subtype; Institution; Interleukin-1 beta; Interleukin-10; Kansas; Knowledge; Lead; Life Expectancy; Measures; Mediating; Memory; Memory B-Lymphocyte; Molecular; Native Americans; Natural Killer Cells; Obesity; Oklahoma; Organ; Outcome; Pathogenesis; Patients; Pharmaceutical Preparations; Pneumonia; Positioning Attribute; Prevalence; Research; Resources; Respiratory distress; Risk; Sampling; Serum; Severe Acute Respiratory Syndrome; Severity of illness; Symptoms; T-Cell Receptor; T-Lymphocyte; T-Lymphocyte Epitopes; T-cell receptor repertoire; TNF gene; TXNIP gene; Texas; Time; Tribes; United States; Vaccines; Verapamil; Virus; comorbidity; cytokine; experience; high risk; individual response; monocyte; mortality; multidisciplinary; neutralizing antibody; prediction algorithm; programmed cell death protein 1; response; transcriptome; tribal health; urban Native American; vaccine trial; γδ T cells

Project Summary The continuing prevalence of SARS-CoV-2 coronavirus cases has led to an urgent need to develop strategies for identifying patients who are likely to have mild vs. severe disease to optimally allocate health care resources. It is also critical that we understand why certain patients develop severe disease. One possible mechanism is through antibody-dependent enhancement (ADE) a phenomenon well documented for other viruses including SARS. In order to develop safe and effective vaccines, it is essential that we determine whether the humoral immune response to Covid-19 induces antibodies that can mediate ADE and to understand which aspects of the immune response to the virus correlate with good clinical outcomes. Addressing this knowledge gap quickly is necessary to inform vaccine trials, which are already underway or are about to start. Our multidisciplinary team has the expertise to address the issues described above. As an independent non-profit research institution, we are nimble and responsive to evolving health needs. Besides studying a spectrum of patients from across Oklahoma, we are uniquely positioned to look at the consequences of SARS- CoV-2 infection for Native Americans. Native Americans have the shortest life expectancy of any ethnic group in the US with higher rates of nearly every co-morbidity associated with higher mortality with SARS-CoV-2 infection (obesity, diabetes, heart disease, and hypertension). Oklahoma is home to 39 federally recognized tribes and has the 2nd highest number of American Indians (482,760 according to the 2010 census, and highest percentage, >10%) in the US. Through our Oklahoma Shared Clinical and Translational Resources (OSCTR), we have partnerships with 5 major tribes, urban Indian clinics and the Southern Plains Tribal Health Board representing all tribes in Oklahoma, Texas and Kansas. Through these and other interactions, we have strong ties to obtain samples from Native Americans with SARS-CoV-2 infection and exposure. Specific Aims 1. Identify biomarkers and mechanisms of severe Covid-19 disease pathogenesis 2. Characterize the humoral immune response to SARS-CoV-2 infection 3. Characterize the T cell immune response to SARS-CoV-2 infection Whenever feasible, we will compare the responses of Native Americans to those of European Americans to determine whether Native Americans experience worse outcomes to SARS-CoV-2 infection and if so, which parts of the immune response is/are suboptimal. We will also compare the responses of individuals with mild vs. severe disease. The knowledge gained should lead to better care for individuals with Covid-19 disease.

项目摘要 SARS-CoV-2冠状病毒病例的持续流行导致迫切需要发展 识别可能患有轻度疾病和严重疾病的患者的策略，以优化健康分配 护理资源。同样重要的是，我们要了解为什么某些患者会患上严重的疾病。一种可能 机制是通过抗体依赖增强(ADE)，这一现象在其他 包括SARS在内的病毒。为了开发安全有效的疫苗，我们必须确定 新冠肺炎诱导的体液免疫应答是否能诱导抗体介导ADE和TTV 了解对病毒的免疫反应的哪些方面与良好的临床结果相关。 迅速解决这一知识差距对于告知疫苗试验是必要的，这些试验已经在进行中或 就要开始了。 我们的多学科团队拥有解决上述问题的专业知识。作为一个独立的 作为非营利性研究机构，我们能够灵活应对不断变化的健康需求。除了学习一门 来自俄克拉何马州各地的患者，我们处于独特的地位，可以看到SARS的后果- 美洲土著人的CoV-2感染。美洲原住民的预期寿命是所有种族中最短的 在美国，几乎所有与SARS-CoV-2高死亡率相关的共病都有较高的发病率 感染(肥胖、糖尿病、心脏病和高血压)。俄克拉荷马州拥有39个联邦认可的 部落，美国印第安人人数第二多(根据2010年人口普查，482,760人，最多 百分比，10%)在美国。通过我们的俄克拉荷马州共享临床和翻译资源(OSCTR)， 我们与5个主要部落、印度城市诊所和南部平原部落健康委员会建立了伙伴关系 代表俄克拉荷马州、德克萨斯州和堪萨斯州的所有部落。通过这些和其他互动，我们拥有强大的 从感染和接触过SARS-CoV-2的美洲原住民身上获取样本。 具体目标 1.确定新冠肺炎重症发病的生物标志物及其发病机制 2.SARS-CoV-2感染的体液免疫反应特征 3.SARS-CoV-2感染后T细胞免疫应答的特征 只要可行，我们就会比较美洲原住民和欧洲美国人的反应，以 确定美洲原住民是否经历了感染SARS-CoV-2的更糟糕的结果，如果是， 免疫反应的某些部分是次优的。我们还将比较轻度和轻度患者的反应。 与严重疾病的对比。所获得的知识应该会导致更好地照顾新冠肺炎患者。