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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.

ASBTRACT概述