Core-003

核心003

• 批准号: 10167304
• 负责人: ELAINE F REED
• 金额: $ 8.91万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-19 至 2021-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10167304
• 关键词: 2019-nCoV; Biological Assay; Biometry; COVID-19; Cessation of life; Characteristics; Clinical; Clonality; Computer Models; Coupled; Critical Illness; Cytomegalovirus; DNA Methylation; Data; Development; Disease; Epigenetic Process; Frequencies; Immune; Immune response; Immunologics; Immunology; Infection; Intubation; Kidney Transplantation; Measures; Mechanics; Morbidity - disease rate; Outcome; Patients; Pneumonia; Resources; Respiratory Failure; Respiratory Signs and Symptoms; Severity of illness; Syndrome; System; T-cell receptor repertoire; Technology; Therapeutic; Time; Transplant Recipients; Upper Respiratory Infections; Viral Antigens; Virus; Virus Diseases; antigen-specific T cells; antiviral immunity; base; clinical phenotype; experience; immune function; mortality; novel; novel diagnostics; prevent; respiratory

The COVID-19 clinical syndrome caused by the SARS-CoV-2 virus has the potential to cause significant morbidity and mortality in previously healthy patients. A significant observation is that although this infection may result in a self-limiting upper respiratory infection or mild pneumonia in some patients, other patients experience progression of respiratory symptoms to requirement of intubation for mechanical respiratory support and death due to severe respiratory failure. This clinical observation strongly suggests that differences in host immunologic response are the determinative factor in clinical outcome. We hypothesize that the proposed systems immunology, biostatistical and computational modeling approaches, coupled with detailed clinical phenotype of hospitalized COVID-19 patients will provide a new framework to interpret the interplay between SARS-CoV-2 virus and the host, and the relationship with clinical outcome. Project 1 will assess the frequency and function of SARS-CoV-2 virus antigen specific T cells and evaluate their breadth and clonality of their TCR repertoire with clinical outcome. Project 2 will determine epigenetic signatures of the immune response to the SARS-CoV-2 virus across short, middle and long-term times and identify DNA methylation- based markers of anti-viral immunity and clinical outcome. With this approach, we will create a unique resource of highly annotated longitudinal data on SARS-CoV-2 virus infection, which will enable the development of novel diagnostic strategies and therapeutics to treat or prevent SARS-CoV-2 virus infection.

由SARS-CoV-2病毒引起的新冠肺炎临床综合征可能会造成显著的 既往健康患者的发病率和死亡率。一个重要的观察结果是，尽管这种感染 在一些患者中可能会导致自限性上呼吸道感染或轻度肺炎，其他患者 呼吸系统症状向机械呼吸插管要求的经验进展 因严重呼吸衰竭而支撑和死亡。这一临床观察强烈表明，不同的 宿主的免疫应答是影响临床预后的决定性因素。我们假设 建议的系统免疫学、生物统计学和计算建模方法，以及详细的 住院新冠肺炎患者的临床表型将提供一个新的框架来解释这种相互作用 SARS-CoV-2病毒与宿主的关系及其与临床转归的关系项目1将评估 SARS-CoV-2病毒抗原特异性T细胞的频率和功能及其广度和克隆性评价 他们的TCR曲目与临床结果的关系。项目2将确定免疫的表观遗传学特征 对SARS-CoV-2病毒的短期、中期和长期反应，并鉴定DNA甲基化- 基于抗病毒免疫和临床结果的标记物。通过这种方法，我们将创建一个独特的资源 关于SARS-CoV-2病毒感染的高度注释的纵向数据，这将使 治疗或预防SARS-CoV-2病毒感染的新诊断策略和治疗方法。