Molecular and Immunologic Analysis of the Pathobiology of Human Anthrax

摘要/文摘

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.