Diversity and Determinants of the Immune-Inflammatory Response to SARS-CoV-2

SARS-CoV-2 免疫炎症反应的多样性和决定因素

基本信息

批准号：
10222432
负责人：
Susan Cheng
金额：
$ 338.63万
依托单位：
CEDARS-SINAI MEDICAL CENTER
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：
2020-09-30 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10222432
关键词：
2019-nCoV Acute Address Affect Antibodies Area Autoimmune Diseases Basic Science COVID-19 California Caring Characteristics Chronic Disease Clinical Clinical Sciences Cohort Studies Collaborations Communities Coronavirus Data Data Analyses Data Collection Disease Enrollment Ensure Epidemiologist Evaluation Evaluation Studies Exposure to Foundations Funding Goals Health Health Personnel Health system Healthcare Systems Home environment Immune Immunity Immunologist Individual Infection Inflammatory Response Infrastructure Institution Knowledge Los Angeles Malignant Neoplasms Metabolic Diseases Minority Molecular Profiling Natural History Nature Outcome Patients Pattern Persons Population Heterogeneity Population Sciences Populations at Risk Predisposition Public Health Publishing Recovery Recovery of Function Reporting Request for Applications Research Research Personnel Research Project Grants Resources Risk Scientific Advances and Accomplishments Scientist Seeds Seroprevalences Signal Transduction Structure Subgroup Techniques Therapeutic Translational Research Viral Virus Vulnerable Populations World Health Organization base biobank clinical phenotype disorder risk experience immune function immune reconstitution innate immune function insight novel operation pandemic disease programs racial and ethnic recruit respiratory response trait translational scientist

项目摘要

ASBTRACT Overview Every day, Californians continue to experience high levels of exposure to the novel severe acute respiratory coronavirus 2 (SARS-CoV-2) virus. There is an ever-growing urgent need to better understand the nature of exposures, course of illness and recovery, and potential for immunity among persons at particularly heightened risk for the worst COVID-19 outcomes. As part of a rapid scientific response to the present public health crisis, we convened on March 18, 2020 a collaborative of frontline clinicians and scientists to form the Coronavirus Risk Associations and Longitudinal Evaluation (CORALE) studies (corale-study.org). We established two base study cohorts with enrollment centered on (i) patients with suspected or confirmed COVID-19 treated in our health system (currently N>8,300) and on (ii) healthcare workers directly or indirectly involved in delivering their care (currently N=6,679). In response to NIH RFA-CA-20-038, we are now highly motivated and prepared to leverage our existing infrastructure to directly address the critical need for comprehensive longitudinal data collection and analyses to advanced our understanding of SARS-CoV-2 risks, the course of disease, the nature of recovery, and the potential for immunity across populations at risk. By establishing the CORALE-SeroNet U54 program, our goal will be to form a robust and sustainable structure of academic activities centered on investigating the responses elicited by SARS-CoV-2 exposure and the extent to which carefully phenotyped clinical and molecular profiles can signal robust immune reconstitution and complete functional recovery. Our study will be centered on the ethnically/racially diverse population served by our health system in Los Angeles, given then critical need for more knowledge regarding the determinants of COVID-19 related risks in these minority subgroups. Our scientific objectives will be achieved by an outstanding collaborative team of clinician-scientists, epidemiologists, immunologists, basic and translational scientists, analytical chemists, and biostatisticians. Leveraging our collective experience, resources, and infrastructure at major academic institutions from across Southern California (Cedars Sinai, UCSD, UCLA, and USC), we will advance the scientific enterprise through the three distinct yet closely integrated research Projects: Project 1 will elucidate the natural history and longitudinal trajectories that represent the diversity of SARS-CoV-2 exposure, infection, recovery, and clinical immunity patterns across the spectrum of persons at risk. Project 2 will investigate the determinants of SARS-CoV-2 response in persons with altered innate immune function, with a focus on individuals with pre-infection susceptibility traits (e.g. metabolic disease states); and, Project 3 will investigate the determinants of SARS- CoV-2 response in persons with altered adaptive immune function, with a focus on individuals with immune- altered status arising from select malignancies, autoimmune disease, and/or their directed therapies. As a whole this research program will integrate population, clinical, translational, and basic science resources with a world- class investigator team to meet the urgent need for new mechanistic insights and therapeutic approaches to address key knowledge gaps regarding SARS-CoV-2 susceptibility and potential for immunity.

摘要概述加州人每天都继续大量接触这种新型严重急性呼吸道疾病冠状病毒 2 (SARS-CoV-2) 病毒。人们越来越迫切需要更好地了解事物的本质暴露程度、病程和恢复情况以及处于特别高水平人群中的免疫力潜力 COVID-19 最坏结果的风险。作为对当前公共卫生危机的快速科学反应的一部分，我们于 2020 年 3 月 18 日召集了一线临床医生和科学家合作，形成了冠状病毒风险关联和纵向评估 (CORALE) 研究 (corale-study.org)。我们建立了两个研究基地入组队列集中于 (i) 在我们健康状况下接受治疗的疑似或确诊的 COVID-19 患者系统（目前 N>8,300）以及 (ii) 直接或间接参与提供护理的医护人员（目前 N=6,679）。为了响应 NIH RFA-CA-20-038，我们现在非常积极并准备利用我们现有的基础设施可以直接满足全面纵向数据收集的关键需求分析以加深我们对 SARS-CoV-2 风险、病程、恢复性质的了解，以及高危人群获得免疫力的潜力。通过建立CORALE-SeroNet U54程序，我们的目标是形成一个稳健且可持续的学术活动结构，以调查暴露于 SARS-CoV-2 引起的反应以及仔细表型临床和分子水平的程度概况可以表明强大的免疫重建和功能的完全恢复。我们的学习将以鉴于当时的迫切需求，我们在洛杉矶的卫生系统所服务的民族/种族多样化人口了解有关这些少数群体中 COVID-19 相关风险决定因素的更多信息。我们的科学目标将由临床医生科学家、流行病学家、免疫学家、基础科学家和转化科学家、分析化学家和生物统计学家。利用我们的南方地区主要学术机构的集体经验、资源和基础设施加利福尼亚州（西达斯西奈分校、加州大学圣地亚哥分校、加州大学洛杉矶分校和南加州大学），我们将通过三个方面推进科学事业独特但紧密结合的研究项目：项目 1 将阐明自然历史和纵向代表 SARS-CoV-2 暴露、感染、恢复和临床免疫多样性的轨迹各种高危人群的模式。项目 2 将调查 SARS-CoV-2 的决定因素先天免疫功能改变的人的反应，重点是感染前的人易感性特征（例如代谢疾病状态）；并且，项目 3 将调查 SARS 的决定因素适应性免疫功能改变的人对 CoV-2 的反应，重点是免疫功能改变的个体由某些恶性肿瘤、自身免疫性疾病和/或其定向治疗引起的状态改变。整体而言该研究计划将人口、临床、转化和基础科学资源与世界范围内的资源整合起来。类研究团队，以满足对新机制见解和治疗方法的迫切需求解决有关 SARS-CoV-2 易感性和免疫潜力的关键知识差距。