Admin-Core-001

管理核心-001

• 批准号: 10709118
• 负责人: Jane C. Figueiredo
• 金额: $ 44万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10709118
• 关键词: 2019-nCoV; Address; Affect; Area; Autoimmune Diseases; Basic Science; COVID-19; COVID-19 risk; COVID-19 susceptibility; COVID-19 treatment; 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; 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; SARS-CoV-2 antibody; SARS-CoV-2 exposure; 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; response; severe COVID-19; trait; translational scientist

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。