Project-002

项目摘要 2019年冠状病毒病（COVID-19）是一种由SARS-CoV-2引起的新兴传染病 病毒在过去的4个月里，这种疾病已经导致120多万美国人患病。然而，在这方面， 几乎没有关于人体细胞对这种病毒的免疫反应的数据。监测动力学和 与COVID-19临床消退相关的细胞免疫反应的广度应该有助于了解 人体在自然感染时对该病原体的免疫反应。我们将评估SARS-CoV-2抗原 在具有不同疾病严重程度的受试者中， USA-WAS 2/2020样菌株或FR-HF 1465/2020样菌株，这两种主要菌株在华盛顿流行 状态我们将检验协调的CD 4+和CD 8+抗原特异性应答是导致 来清除病毒我们还将检验患有严重疾病的受试者和那些 死于该疾病的患者具有功能失调的CD 4 +T细胞应答。我们将使用转录组学分析， 评估全血、大量T细胞和抗原特异性CD 4+和CD 8 + T细胞。数据将根据 与病毒株和疾病严重程度相关。将有三个主要目标：1。抗原特异性免疫特性 在患有严重肺炎、中度疾病和轻度疾病的COVID-19受试者中， USA-WAS 2/2020菌株或FR-HF 1465/2020菌株。2.表征表位特异性免疫应答 在COVID-19受试者中。受试者中抗原特异性CD 4 + T细胞的功能缺陷 严重的疾病将被测试。3.表征COVID-19呼吸道感染的宿主RNA-seq特征 在来自COVID-19感染受试者的全血PBMC、原液和病毒抗原特异性CD 4+和CD 8 + T细胞中， 通过USA-WAS 2/2020菌株或FR-HF 1465/2020样菌株。更好地了解抗原 人类的特异性免疫应答应有助于鉴定用于治疗的有效候选药物 并开发新的疫苗来预防感染。

PROJECT SUMMARY Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that is caused by the SARS-CoV-2 virus. The disease has caused illness in more than 1.2 million Americans within the last 4 months. However, there are almost no data on human cellular immune response towards this virus. Monitoring the kinetics and breadth of cellular immune responses associated with clinical resolution of COVID-19 should shed insight on the human immune response towards this pathogen during natural infection. We will evaluate SARS-CoV-2 antigen specific immune responses in subjects with different degree of disease severity that are infected by either the USA-WAS2/2020 like strain or the FR-HF1465/2020 like strain, the 2 major strains that circulated in Washington state. We will test the hypothesis that coordinated CD4+ and CD8+ antigen specific responses are responsible for clearing of the virus. We will also test the hypothesis that subjects that have severe disease and those that succumb to the disease have dysfunctional CD4+T cell responses. We will use transcriptomics analysis to evaluate whole blood, bulk T cells and antigen specific CD4+ and CD8+ T cells. Data will be stratified according to the viral strains and disease severity. There will be 3 major aims: 1. Characterize of antigen specific immune responses in COVID-19 subjects with severe pneumonia, moderate disease and mild disease, infected by either the USA-WAS2/2020 strain or the FR-HF1465/2020 strain. 2. Characterize epitope specific immune response in subjects with COVID-19. The hypothesis that the functional defect of antigen specific CD4+ T cells in subjects with severe disease will be tested. 3. Characterize host RNA-seq signatures of COVID-19 respiratory infection in whole blood PBMC, bulk and viral antigen-specific CD4+ and CD8+ T cells from COVID-19 subjects infected by either the USA-WAS2/2020 strain or the FR-HF1465/2020 like strain. A better understanding of antigen specific immune responses in human should facilitate the identification of effective drug candidates for treatment and developing new vaccine to prevent infection.