Molecular and Immunologic Analysis of the Pathobiology of Human Anthrax

摘要/摘要 先天性免疫失调导致SARS-CoV-2感染的严重影响。这部小说的独特之处， 新出现的病原体逃避和吸收宿主免疫应答是未知的。更好地理解 在SARS-CoV-2感染中，病毒-宿主相互作用调节先天免疫应答，这将为 治疗干预和疫苗开发。COVID-19的免疫表型评估 队列（IMPACC）研究协调了一个全国性的多机构联盟，收集了详细的临床数据， 来自住院COVID-19感染者的生物样本，目的是识别免疫 与临床疾病进程相关的特征/分子生物标志物，以允许对临床 干预和决策。该补充支持俄克拉荷马州健康科学大学 中心参与IMPACC，以促进COVID-19住院患者的筛查和入组。它还 检验了低密度中性粒细胞中ARID 3a蛋白表达与 在COVID-19感染期间发生的促炎状态。拟议的补充研究在 母授权U19 AI 062629的范围，人类病原学的分子和免疫学分析 炭疽热在此，我们概述了IMPACC研究招募、入组和保留受试者的流程 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。我们集团 先前收集了相同的样本和类似的临床信息，作为先前NIH治疗的一部分， 试验，IRC 005，我们是该研究的最佳招募者（参与的约40个研究中心中的第3个）。另一个假设是- 驱动的实验性低密度中性粒细胞研究将与一个有才华的， 经验丰富的研究者，并将利用相应的临床数据，这些数据将作为 IMPAC研究。因此，拟议的研究不仅将有助于IMPAC研究取得圆满成功， 而且还对冠状病毒与宿主相互作用的基础生物学产生了新的见解， 从SARS-CoV-2中恢复的人之间先天免疫反应差异的机制 需要住院治疗的疾病，以及进展为不良结局或延迟恢复的疾病。

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.