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.

Asbratct概述每天，加利福尼亚人继续经历高水平的新型严重急性呼吸道冠状病毒2（SARS-COV-2）病毒。迫切需要更好地了解暴露，疾病和康复过程以及人与人之间的免疫力的潜力遇到最糟糕的19个结果的风险。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日召集了前线临床医生和科学家的合作者，以形成冠状病毒风险协会和纵向评估（Corale）研究（Corale-Study.org）。我们建立了两个基础研究招生的同伙以（i）疑似或确认的COVID-19在我们健康中治疗的患者中为中心系统（目前n> 8,300）以及（ii）直接或间接参与提供护理的医疗保健工人（目前n = 6,679）。为了响应NIH RFA-CA-20-038，我们现在很有动力并准备好利用我们现有的基础架构直接解决了对全面纵向数据收集和分析以提高我们对SARS-COV-2风险的理解，疾病的进程，恢复性质，以及处于风险的人群之间的免疫力。通过建立Corale-Seronet U54计划，我们的目标是建立一个以研究为中心的学术活动的强大而可持续的结构 SARS-COV-2暴露引起的反应以及精心表型临床和分子的响应程度轮廓可以发出稳健的免疫重建和完整的功能恢复。我们的研究将集中鉴于我们的卫生系统在洛杉矶提供的种族/种族多样化的人口有关这些少数亚组中相关风险的决定因素的更多知识。我们的科学目标将由一个杰出的临床医生，流行病学家，流行病学家，流行病学家的合作团队实现免疫学家，基本和转化科学家，分析化学家和生物统计学家。利用我们的来自南部的主要学术机构的集体经验，资源和基础设施加利福尼亚（Cedars Sinai，UCSD，UCLA和USC），我们将通过这三个企业推进科学企业独特但紧密整合的研究项目：项目1将阐明自然历史和纵向代表SARS-COV-2暴露，感染，恢复和临床免疫的多样性的轨迹跨风险的人的模式。项目2将研究SARS-COV-2的决定因素对先天免疫功能改变的人的反应，重点是感染的个体敏感性特征（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的COV-2反应，重点是因某些恶性肿瘤，自身免疫性疾病和/或其定向疗法而产生的状态改变。整体该研究计划将将人口，临床，转化和基础科学资源与世界相结合 - 班级调查员团队迫切需要对新机械见解和治疗方法的需求解决有关SARS-COV-2敏感性和免疫力潜力的关键知识差距。