Experimental and Computational Analysis of the Human Epidemiology and Response to SARS-CoV-2 (HEROS) Cohort

人类流行病学和对 SARS-CoV-2 (HEROS) 队列反应的实验和计算分析

• 批准号: 10359637
• 负责人: DONALD YM LEUNG
• 金额: $ 563.49万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-28 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10359637
• 关键词: Applications Grants; Area; Asthma; Atopic Dermatitis; Bacterial Infections; Biological; Birth; Clinical; Clinical Research; Clinical Trials; Cohort Studies; Collaborations; Cutaneous; Data Coordinating Center; Defect; Development; Ensure; Epithelial; Food Hypersensitivity; Functional disorder; Funding; General Population; Goals; Grant; Health; Hospitalization; Host Defense; Hypersensitivity; Immune; Immune response; Immunity; Impairment; Inflammation; Infrastructure; Interleukin-1; Interleukin-13; Interleukin-4; Intervention; Intervention Studies; Leadership; Long-Term Effects; Morbidity - disease rate; Multi-site clinical study; National Institute of Allergy and Infectious Disease; Observational Study; Operations Research; Outcome; Pathway interactions; Patients; Performance; Phenotype; Proteomics; Protocols documentation; Quality of life; Research; Research Personnel; Resources; Sampling; Skin; Structure; Study Subject; Systems Biology; Therapeutic Intervention; Time; Topical Corticosteroids; Translating; United States National Institutes of Health; Virus Diseases; Work; atopy; biobank; chronic inflammatory skin; data integrity; design; dysbiosis; evidence base; follower of religion Jewish; lipidomics; microbial; microbiome; microbiota transplantation; novel; novel strategies; operation; organizational structure; programs; response; rho; safety study; single-cell RNA sequencing; skin barrier; skin disorder; skin microbiome; systemic inflammatory response; targeted treatment; transcriptomics; treatment response

PROJECT SUMMARY Atopic dermatitis (AD) is the most common chronic inflammatory skin disease in the general population. AD is associated with defective skin barrier function, microbial and viral dysbiosis, as well as various cutaneous immune abnormalities including type 2 inflammation and decreased cutaneous host defense. The Atopic Dermatitis Research Network-Leadership Center (ADRN-LC) provides that scientific strategy and organizational structure to elucidate mechanisms of skin barrier dysfunction, cutaneous immune responses, and viral determinants of atopic dermatitis (AD). An emerging virus with potential direct implications to AD and other allergic diseases is SARS-CoV-2. SARS-CoV-2 is the virus which causes COVID-19 illnesses, which are rapidly affecting humans around the globe. While initial epidemiological data have focused on cases that resulted in severe respiratory disease seen predominantly in adults, little information regarding the infection burden in children is available. This is complicated by the observation that many children experience asymptomatic infections. Undocumented, and likely infectious, cases could result in exposure to a far greater proportion of the community than would otherwise occur. Indeed, it has been proposed that undocumented (or silent) infections are the source for almost 80% of documented infections; thus, it is critical to determine the silent and symptomatic infection rate in children and to understand why they develop less severe or asymptomatic disease. To overcome challenges for clinical study implementation imposed by current healthcare access restrictions, this surveillance study will enroll and prospectively observe eligible children that are current participants in NIH-funded pediatric research studies and their family members. We will collect nasal swabs from all subjects in 2 week intervals for a 4 month period, again at 6 months, and during respiratory illnesses. Our group will act as the laboratory processing and analysis site for the study. We will extract DNA/RNA from all swabs and perform a qPCR assay test for the SARS-Cov-2 virus. This will allow us to determine the incidence of the SARS-Cov-2 in the U.S. population and how it varies between children and adults, and those with asthma and other lung diseases. Secondly, we will perform Dual RNA-seq on RNA from nasal swabs to determine the host epithelial and immune cell response to infection with SARS-Cov-2 and COVID-19 respiratory illnesses. This data will also allow us to identify different strains of the SARS-Cov-2 virus circulating in the U.S., their geographical distribution, and how these strains relate to COVID-19 illness severity.

项目总结 特应性皮炎(AD)是普通人群中最常见的慢性炎症性皮肤病。广告是 与皮肤屏障功能缺陷、微生物和病毒代谢异常以及各种皮肤 免疫异常，包括2型炎症和皮肤宿主防御能力下降。话题 皮炎研究网络领导中心(ADRN-LC)提供科学策略和 组织结构来阐明皮肤屏障功能障碍的机制，皮肤免疫反应， 和特应性皮炎(AD)的病毒决定因素。一种对阿尔茨海默病有潜在直接影响的新兴病毒 和其他过敏性疾病是SARS-CoV-2。SARS-CoV-2是导致新冠肺炎疾病的病毒， 它们正迅速影响着全球各地的人类。虽然最初的流行病学数据集中在病例 这导致了严重的呼吸道疾病，主要见于成年人，关于感染的信息很少。 儿童负担是可用的。这一点由于许多儿童所经历的观察而变得复杂 无症状感染。未记录的、可能具有传染性的病例可能会导致接触到更大的 社区的比例超过了其他情况下会出现的比例。事实上，有人提出，未登记的(或 无声)感染是近80%有记录的感染的源头；因此，确定 儿童无症状和有症状的感染率，并了解为什么他们发展得不那么严重或 无症状的疾病。克服当前临床研究实施面临的挑战 医疗保健准入限制，这项监测研究将招募并前瞻性观察符合条件的儿童 目前是NIH资助的儿科研究的参与者和他们的家人。我们会收集鼻音 从所有受试者身上取拭子，间隔2周，为期4个月，同样在6个月，并在呼吸期间 疾病。我们小组将作为这项研究的实验室处理和分析地点。我们将提取 从所有拭子中提取DNA/RNA，并进行SARS-CoV-2病毒的qPCR检测。这将使我们能够 确定SARS-CoV-2在美国人群中的发病率，以及儿童和 成人，以及哮喘和其他肺部疾病患者。其次，我们将对来自的RNA进行双重RNA-seq 鼻拭子以确定宿主上皮细胞和免疫细胞对感染SARS-CoV-2和 新冠肺炎呼吸系统疾病。这些数据还将使我们能够识别不同的SARS-CoV-2病毒株 在美国的流行情况，它们的地理分布，以及这些菌株与新冠肺炎疾病严重程度的关系。