Core-004

核心004

• 批准号: 10167305
• 负责人: ELAINE F REED
• 金额: $ 7.8万
• 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/10167305
• 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COVID-19临床综合征有可能导致严重的 发病率和死亡率。一个重要的观察是，虽然这种感染 在某些患者中可能导致自限性上呼吸道感染或轻度肺炎， 呼吸道症状进展至需要插管进行机械呼吸 支持和死亡，由于严重呼吸衰竭。这一临床观察强烈表明， 宿主免疫应答是临床预后的决定性因素。我们假设 提出了系统免疫学，生物统计学和计算建模方法，再加上详细的 住院COVID-19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病毒与宿主之间的关系，以及与临床结局的关系。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，并评估其宽度和克隆性 与临床结果的关系。项目2将确定免疫系统的表观遗传特征 对SARS-CoV-2病毒的短期、中期和长期反应，并确定DNA甲基化- 基于抗病毒免疫和临床结果的标志物。通过这种方法，我们将创造一种独特的资源， 关于SARS-CoV-2病毒感染的高度注释的纵向数据，这将使开发 治疗或预防SARS-CoV-2病毒感染的新型诊断策略和疗法。