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Asthma Endotypes: Mechanisms and Consequences for Airway Epithelium and Mucus

哮喘内型：气道上皮和粘液的机制和后果

基本信息

批准号：
10371127
负责人：
David J Erle
金额：
$ 179.79万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
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：
2020-05-08 至 2023-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10371127
关键词：
2019-nCoV Adult Affect Age Aspirate substance Asthma Biological Biological Assay COVID-19 COVID-19 pandemic COVID-19 patient Case Fatality Rates China Chronic Clinical Clinical Research Clinical Trials Communities Coronavirus DNA Sequencing Facility Development Diabetes Mellitus Disease Disease Outcome Elements Enrollment Environmental Risk Factor Family General Hospitals Genetic Genetic Risk Health Healthcare Systems Hypertension Immune System Diseases Immune response Immunologics Immunophenotyping Individual Institution Intervention Investigation Laboratories Lung diseases Medical Medical center Metagenomics Methods Mucous body substance Myocardial Ischemia National Institute of Allergy and Infectious Disease Nature Onset of illness Outcome Participant Pathogenicity Patients Peripheral Blood Mononuclear Cell Personal Satisfaction Phage Display Phage ImmunoPrecipitation Sequencing Pharmaceutical Preparations Pneumonia Prognostic Marker Recurrence Resources Risk Factors SARS-CoV-2 infection Sample Size Sampling San Francisco Serology Serum Severity of illness Site Therapeutic Agents Variant Viral Load result Virus airway epithelium base biomarker development clinical center clinical risk cohort comorbidity design effective therapy endotracheal global health health care availability improved inclusion criteria member mortality neutralizing antibody neutralizing vaccine next generation sequencing novel novel therapeutics novel virus pandemic disease pathogen peripheral blood prospective respiratory response social structure therapeutic target transcriptome sequencing trauma centers welfare

项目摘要

PROJECT SUMMARY/ABSTRACT COVID-19, the pandemic illness caused by the novel virus SARS-CoV-2, is a serious respiratory illness that has high infectivity and a mortality rate that varies from <1% to up to 20% depending on underlying risk factors. Indeed, disease severity varies markedly based on recognized clinical risk factors (age and co-morbidities). The biological underpinnings of this clinical variability are unknown but likely relate to variation in both the virus and the host response. A detailed understanding of the risk factors for severe disease, including genetic and environmental factors and the nature of the host immunological response, is essential for the development of prognostic biomarkers and effective therapies. To meet this urgent need we propose to help develop and to participate in the IMPACC multi-center longitudinal clinical study of hospitalized patients with COVID-19 and to immunophenotype participants using shared immunological methods that will be designed an carried out by core laboratories at UCSF and at other participating institutions. Our specific aims are 1) to develop a prospective observational convenience cohort of adult subjects hospitalized with known or presumptive COVID-19, 2) to use this cohort to describe the relationship between specific immunologic assessments and clinical course of COVID-19 in hospitalized patients, and 3) to implement three core laboratories at UCSF to support immunophenotyping in this multicenter cohort. These core laboratories will perform bulk RNA sequencing of blood peripheral blood mononuclear cells (PBMC), bulk metagenomic next-generation sequencing (mNGS) on endotracheal aspirate samples, and serologic phage display assays (PhIP-Seq). Successful completion of these aims will yield critical information regarding the relationship between viral load, host immunological responses, and poor clinical outcomes that are urgently needed for biomarker development and rational therapeutic targeting. In addition, the cellular samples banked in this study may directly contribute to the development of neutralizing antibodies and vaccine strategies that will be our ultimate defense against recurrence of this extraordinary pandemic. A rapid and robust scientific and medical response of the type proposed by the NIAID and the academic community in this consortium is an essential element of a broad response required to protect the health and well-being of all individuals, our health care system, and the broader social structures that maintain global health and welfare.

项目总结/文摘