Molecular and Immunologic Analysis of the Pathobiology of Human Anthrax

人类炭疽病病理学的分子和免疫学分析

• 批准号: 10213407
• 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
• 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/10213407
• 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

Summary/Abstract 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 hypothesis- driven 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.

摘要/摘要 先天免疫失调导致SARS-CoV-2感染的严重后果。这部小说独特的方式， 新出现的病原体逃避和利用宿主的免疫反应尚不清楚。更好地理解 病毒-宿主相互作用调节SARS-CoV-2感染的先天免疫反应将为 治疗干预和疫苗开发。新冠肺炎的免疫表型评价 队列研究(IMPACC)协调一个全国性的多机构联盟，收集详细的临床数据和 来自住院的新冠肺炎感染者的生物样本，目的是鉴定免疫 与临床病程相关的信号/分子生物标记物，以便确定临床的优先顺序 干预和决策。本增刊支持俄克拉荷马大学健康科学 中心参与IMPACC，以促进新冠肺炎患者的筛查和登记。它还 检验了低密度中性粒细胞中ARID3a蛋白表达与 新冠肺炎感染期间出现的促炎状态。拟议的补充研究是在 父母资助范围U19AI062629，人类病理生物学的分子和免疫学分析 炭疽热。在这里，我们将概述我们将招募、登记和保留IMPACC研究对象的过程 在我们的健康科学中心，并获得所需的临床信息和实验室样本。我们的团队 以前收集的样本和类似的临床信息与之前NIH治疗的部分相同 试验，IRC005，我们是该研究的顶级参与者(约40个参与站点中的第三个)。另一个假设是-- 驱动型实验性低密度中性粒细胞研究将与有才华的和 经验丰富的调查员，并将利用相应的临床数据，这些数据将作为 IMPACC研究。因此，拟议的研究不仅将有助于方案执行委员会的研究取得圆满成功， 但也为冠状病毒与宿主相互作用的基本生物学提供了新的见解，并可能揭示一种新的 SARS-CoV-2恢复者与恢复者先天免疫应答差异的机制 需要住院治疗的疾病，以及进展为不良结局或恢复延迟的疾病。