Administrative Core

行政核心

基本信息

批准号：
10221080
负责人：
Kenneth Mark Coggeshall
金额：
$ 47.65万
依托单位：
OKLAHOMA MEDICAL RESEARCH FOUNDATION
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10221080
关键词：
2019-nCoV ARID3A gene Adult Respiratory Distress Syndrome Age Anthrax disease Antiviral Agents Autopsy Biological Biological Markers Biology COVID-19 Cells Cessation of life Characteristics Chronic Clinical Clinical Course of Disease Clinical Data Clinical Distribution Cohort Studies Collaborations Coronavirus Data Decision Making Deterioration Diabetes Mellitus Disease Enrollment Epigenetic Process Failure Funding Goals Grant Health Sciences Heart Diseases Hospitalization Human Immune Immune response Immune system Immunologics Immunophenotyping Individual Infection Innate Immune Response Innate Immune System Inpatients Institution Interferon-alpha Interleukin-6 Intervention Knowledge Laboratories Lung Lung diseases Measures Medical Molecular Molecular Profiling Oklahoma Outcome Patient Care Patients Predisposition Prevention Process Proteins Recovery Research Research Personnel Resources Risk Sampling Secondary to Site Syndrome System Talents Testing Therapeutic Intervention Therapeutic Trials United States National Institutes of Health Universities Viral Viral Load result Viral Pneumonia Virus clinical care clinical predictors clinical risk cohort cytokine release syndrome density experience experimental study follow-up insight molecular marker neutrophil novel novel coronavirus parent grant pathogen pneumocyte protein expression recruit response screening targeted treatment therapeutic vaccine therapy development vaccine development virus host interaction

项目摘要

Innate immune dysregulation causes the severe effects of SARS-CoV-2 infections. The unique ways this novel, emergent pathogen evades and co-opts the host immune response is not known. A better understanding of the virus-host interactions regulating the innate immune response in SARS-CoV-2 infections will provide a basis for therapeutic interventions and vaccine development. The Immunophenotyping Assessment in a COVID-19 Cohort (IMPACC) study coordinates a national, multi-institution consortium, collecting detailed clinical data and biologic samples from hospitalized COVID-19 infected individuals, with the goal of identifying immune signatures/molecular biomarkers associated with clinical disease course, to allow the prioritization of clinical interventions and decision making. This supplement supports the University of Oklahoma Health Sciences Centers’ participation in IMPACC to facilitate screening and enrollment of inpatients with COVID-19. It also examines the hypothesis that that ARID3a protein expression in low-density neutrophils is associated with the proinflammatory state that occurs during COVID-19 infection. The proposed supplement research is within the scope of the parent grant U19AI062629, Molecular and Immunologic Analysis of the Pathobiology of Human Anthrax. Here, we outline the process by which we will recruit, enroll and retain subjects for the IMPACC study at our health sciences center, and obtain the clinical information and laboratory samples required. Our group has previously collected the same samples and similar clinical information as part of a previous NIH therapeutic trial, IRC005, and we were a top enroller (3rd of ~40 sites participating) in that study. The additional hypothesisdriven experimental low-density neutrophil study will be performed in collaboration with a talented and experienced investigator, and will exploit the corresponding clinical data that will be collected as part of the IMPACC study. Thus, the proposed study will not only help the IMPACC study towards a successful conclusion, but also generate new insights into the basic biology of coronavirus-host interactions and may reveal a novel mechanism for the differences in the innate immune responses to SARS-CoV-2 between those that recover from disease requiring hospitalization, and those that progress to poor outcomes or delayed recovery.

先天免疫失调会引起SARS-COV-2感染的严重作用。这本小说的独特方式，新兴的病原体逃避和同事宿主免疫反应尚不清楚。更好地理解调节SARS-COV-2感染中先天免疫反应的病毒 - 宿主相互作用将为您提供基础治疗干预措施和疫苗开发。 COVID-19中的免疫表型评估队列（IMPACC）研究协调一个国家多机构财团，收集详细的临床数据和来自住院的Covid-19受感染个体的生物样品，目的是识别免疫与临床疾病病程相关的特征/分子生物标志物，以便优先考虑临床干预和决策。这种补充支持俄克拉荷马大学健康科学中心参与IMPACC，以促进COVID-19的住院患者筛查和入学。也是如此检验了以下假设：低密度嗜中性粒细胞中的Arid3a蛋白表达与促炎状态发生在Covid-19感染期间。拟议的补充研究在父母的范围U19AI062629，人类病理生物学的分子和免疫学分析炭疽病。在这里，我们概述了我们将招募，注册和保留主题进行IMPACC研究的过程在我们的健康科学中心，获取所需的临床信息和实验室样本。我们的小组以前已经收集了相同的样本和相似的临床信息作为先前的NIH治疗的一部分试验，IRC005，我们是该研究的最高入学者（参加约40个地点的第三名）。其他假设驱动的实验性低密度嗜中性粒细胞研究将与才华横溢的人合作进行经验丰富的研究者，并将探索将作为该数据收集的相应临床数据 IMPACC研究。这是拟议的研究，不仅将有助于IMPACC研究取得成功的结论，但也产生了对冠状病毒 - 宿主相互作用的基本生物学的新见解，并可能揭示出一种小说从中恢复过的人对SARS-COV-2的先天免疫反应差异的机制需要住院的疾病，以及那些疾病的疾病，而那些疾病会恢复不良或恢复延迟。