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Genetic and Immuno-inflammatory Drivers of Post-acute Pulmonary Sequelae of SARS-CoV-2

SARS-CoV-2 急性后肺部后遗症的遗传和免疫炎症驱动因素

基本信息

批准号：
10587075
负责人：
Steven B Abramson
金额：
$ 85.38万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-02-05 至 2028-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10587075
关键词：
2019-nCoV Acute Acute Disease Affect Antibodies Antibody Response Autoantibodies Autoimmune Autoimmune Process Automobile Driving Biological Markers Black race COVID-19 complications COVID-19 patient Carbon Monoxide Categories Characteristics Chronic Clinical Clinical Data Data Development Diffusion Disease Ethnic Origin Etiology Fatigue Feces Frequencies Functional disorder Future Genetic Genetic Polymorphism Genetic Predisposition to Disease Genetic Processes Genetic Risk Genetic Variation Genotype Goals Immune response Immunologics Impairment Incidence Infection Infection Control Inflammatory Inflammatory Response Interferons Interleukin-1 Long COVID Long-Term Effects Longitudinal Studies Lung Lung CAT Scan Measures Minority Groups Nasopharynx Neighborhoods Neurocognitive Outcome Pathogenicity Pathway interactions Patient Outcomes Assessments Patients Phenotype Physiological Play Post-Acute Sequelae of SARS-CoV-2 Infection Process Protocols documentation Proxy Pulmonary Fibrosis Pulse Oximetry Quality of life Questionnaires RNA Race Recording of previous events Role SARS-CoV-2 infection Severities Shortness of Breath Social outcome Socioeconomic Status Symptoms Syndrome Telephone Testing Tissues Total Lung Capacity United States Agency for Healthcare Research and Quality Vaccination Vital capacity Walking X-Ray Computed Tomography acute infection black patient breakthrough infection cognitive testing cohort cytokine deprivation design genetic association health disparity idiopathic pulmonary fibrosis immunoregulation indexing long term consequences of COVID-19 novel patient stratification persistent symptom post SARS-CoV-2 infection post-COVID-19 primary endpoint pulmonary function pulmonary symptom risk variant secondary outcome social determinants social health determinants therapeutic target

项目摘要

ABSTRACT The goal of this proposal will be to study the frequency, chronicity and etiology of post-acute sequelae of SARS CoV-2 with protocols designed to characterize genetic and immuno-inflammatory factors that influence post- COVID complications. We will establish a cohort of 1200 or more deeply phenotyped SARS CoV-2 patients in order to determine the long-term effects of COVID-19 infection in distinct PASC cohorts. Patients will be categorized by the presence or absence of pulmonary symptoms. We will focus on changes in pulmonary lung function (DLCO and FVC, TLC) and 6-minute walk test (6MWT) distance at 3, 6, and 12 months and bi- annually thereafter for 5 years. To assess for progressive pulmonary fibrosis we will include x-rays and computerized tomography (CT) of the lung. To explore pathogenic mechanisms we will: 1) determine whether specific cytokine levels associate with the severity or progression of PASC-associated disease; and, 2) determine whether there is a characteristic autoantibody profile, including anti-cytokine antibodies, in PASC patients; 3) perform Global Diversity Array (GDA) chip analysis on 1200 patients to develop an unbiased genetic risk score for PASC; 4) determine whether specific genotypes: a) influence the severity or chronicity of PASC, including the development of Idiopathic Pulmonary Fibrosis or b) contribute to the sustained immunological responses in PASC patients. Finally, we will determine whether there is a genetic association with PASC syndromes that varies across self-identified race/ethnicity (SIRE). Taken together, these novel studies are intended to better understand pathogenetic mechanisms of disease, which can lead to the identification of therapeutic targets and strategies for patients with post-acute sequelae.

抽象的该提案的目标是研究 SARS 急性后遗症的频率、慢性性和病因学 CoV-2 的方案旨在表征影响后遗症的遗传和免疫炎症因素新冠肺炎并发症。我们将建立一个包含 1200 个或更多深度表型 SARS CoV-2 的队列患者，以确定 COVID-19 感染对不同 PASC 队列的长期影响。患者将根据是否存在肺部症状进行分类。我们重点关注肺部的变化肺功能（DLCO 和 FVC、TLC）和 3、6 和 12 个月以及双倍时的 6 分钟步行测试 (6MWT) 距离此后每年一次，持续 5 年。为了评估进行性肺纤维化，我们将包括 X 光检查和肺部计算机断层扫描（CT）。为了探索致病机制，我们将：1）确定是否特定细胞因子水平与 PASC 相关疾病的严重程度或进展相关；以及，2) 确定 PASC 中是否存在特征性自身抗体谱，包括抗细胞因子抗体患者; 3) 对 1200 名患者进行全球多样性阵列 (GDA) 芯片分析，以开发公正的基因 PASC 风险评分； 4) 确定特定基因型是否： a) 影响 PASC 的严重性或慢性性，包括特发性肺纤维化的发展或 b) 有助于持续的免疫学 PASC 患者的反应。最后，我们将确定是否与 PASC 存在遗传关联不同种族/族裔 (SIRE) 之间存在差异的综合症。总而言之，这些新颖的研究是旨在更好地了解疾病的发病机制，从而识别急性后遗症患者的治疗目标和策略。