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.

项目摘要 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，微生物和病毒性营养不良以及各种皮肤的缺陷有关 免疫异常，包括2型炎症和皮肤宿主防御降低。特应当 皮肤炎研究网络领导中心（ADRN-LC）提供了科学策略和 组织结构以阐明皮肤屏障功能障碍，皮肤免疫反应的机制， 以及特应性皮炎的病毒决定因素（AD）。与AD有潜在直接影响的新兴病毒 其他过敏性疾病是SARS-COV-2。 SARS-COV-2是导致COVID-19疾病的病毒， 这会迅速影响全球人类。最初的流行病学数据集中在病例上 这导致主要在成年人中出现严重的呼吸系统疾病，几乎没有有关感染的信息 有儿童负担。许多孩子经历的观察变得复杂 无症状感染。无证件且可能感染的情况可能导致暴露更大 社区的比例比以其他方式发生的比例。确实，已经提出了无证件（或 无声）感染是近80％的记录感染的来源；因此，确定 儿童的沉默和有症状的感染率，并了解为什么他们出现不那么严重或 无症状疾病。克服对当前施加的临床研究实施的挑战 医疗保健访问限制，这项监视研究将注册并前瞻性地观察到合格的儿童 目前是NIH资助的儿科研究及其家人的参与者。我们将收集鼻 在2周间隔4个月内，在6个月和呼吸道期间，所有受试者的拭子在4个月的时间内再次 疾病。我们的小组将充当研究的实验室处理和分析地点。我们将提取 来自所有拭子的DNA/RNA，并对SARS-COV-2病毒进行QPCR测定测试。这将使我们能够 确定美国人群中SARS-COV-2的发生率以及儿童之间的变化 成人，以及患有哮喘和其他肺部疾病的患者。其次，我们将对从RNA进行双RNA-seq 鼻拭子确定宿主上皮和免疫细胞对SARS-COV-2感染的反应，并 COVID-19-19。呼吸道疾病。这些数据还将使我们能够识别SARS-COV-2病毒的不同菌株 在美国循环，它们的地理分布以及这些菌株与Covid-19的疾病严重程度如何相关。