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 临床综合征有可能引起严重后果 以前健康的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 某些患者可能会出现自限性上呼吸道感染或轻度肺炎，而另一些患者则可能会出现自限性上呼吸道感染或轻度肺炎。 经历呼吸道症状进展到需要插管进行机械呼吸 因严重呼吸衰竭而死亡。这一临床观察强烈表明差异 宿主免疫反应是临床结果的决定性因素。我们假设 提出的系统免疫学、生物统计和计算建模方法，以及详细的 住院 COVID-19 患者的临床表型将为解释相互作用提供新的框架 SARS-CoV-2 病毒与宿主之间的关系以及与临床结果的关系。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，并评估其广度和克隆性 他们的 TCR 库与临床结果。项目 2 将确定免疫的表观遗传特征 对 SARS-CoV-2 病毒的短期、中期和长期反应并识别 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，我们将创建独特的资源 有关 SARS-CoV-2 病毒感染的高度注释的纵向数据，这将有助于开发 治疗或预防 SARS-CoV-2 病毒感染的新诊断策略和疗法。