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患病率迫切需要发展 识别可能患有轻度和严重疾病以最佳分配健康的患者的策略 护理资源。我们了解为什么某些患者会出现严重疾病，这也是至关重要的。一个可能 机制是通过抗体依赖性增强（ADE）的一种现象 包括SAR的病毒。为了开发安全有效的疫苗，我们必须确定 对1900-19的体液免疫反应是否诱导可以介导ADE和对的抗体 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。 快速解决此知识差距是为了告知已经在进行的疫苗试验或 即将开始。 我们的多学科团队具有解决上述问题的专业知识。作为独立 非营利研究机构，我们对不断发展的健康需求敏捷而反应。除了学习一个 来自俄克拉荷马州各地的患者的范围​​，我们的位置很独特，可以研究SARS-的后果 美国原住民的COV-2感染。美洲原住民的预期寿命最短 在美国，与SARS-COV-2相关的几乎每个合并症的比率较高 感染（肥胖，糖尿病，心脏病和高血压）。俄克拉荷马州拥有39个联邦认可的家园 部落，拥有美国印第安人的第二高（根据2010年人口普查为482,760，最高 美国百分比> 10％）。通过我们的俄克拉荷马州共享临床和转化资源（OSCTR）， 我们与5个主要部落，城市印度诊所和南平原部落卫生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。通过这些互动和其他互动，我们有很强的 与SARS-COV-2感染和暴露的美洲原住民获取样品的关系。 具体目标 1。识别严重的Covid-19疾病发病机理的生物标志物和机制 2。表征对SARS-COV-2感染的体液免疫反应 3。表征T细胞对SARS-COV-2感染的免疫反应 每当可行的情况下，我们都会将美洲原住民与欧洲人的反应进行比较 确定美洲原住民是否经历SARS-COV-2感染的结果更糟，如果是 免疫反应的一部分是/次优。我们还将比较温和的个体的反应 与严重疾病。获得的知识应导致对Covid-19疾病患者的更好护理。