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.

项目概要 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 与皮肤屏障功能缺陷、微生物和病毒失调以及各种皮肤病有关 免疫异常，包括 2 型炎症和皮肤宿主防御能力下降。特应性 皮炎研究网络领导中心 (ADRN-LC) 提供科学策略和 组织结构，以阐明皮肤屏障功能障碍、皮肤免疫反应的机制， 和特应性皮炎（AD）的病毒决定因素。一种对AD有潜在直接影响的新兴病毒 和其他过敏性疾病一样的是SARS-CoV-2。 SARS-CoV-2 是导致 COVID-19 疾病的病毒， 正在迅速影响全球人类。虽然最初的流行病学数据集中于病例 导致主要见于成人的严重呼吸道疾病，有关感染的信息很少 儿童的负担是可用的。许多孩子经历过的观察使情况变得复杂 无症状感染者。无证且可能具有传染性的病例可能会导致接触更大范围的病毒 社区的比例高于其他情况下发生的比例。事实上，有人提议无证（或 无声）感染是近 80% 已记录感染的来源；因此，确定 儿童无症状和有症状感染率，并了解为什么他们的病情发展得不那么严重或 无症状疾病。克服当前临床研究实施面临的挑战 医疗保健获取限制，这项监测研究将招募并前瞻性观察符合条件的儿童 是 NIH 资助的儿科研究的当前参与者及其家庭成员。我们将收集鼻腔 在 4 个月、6 个月以及呼吸期间每隔 2 周对所有受试者进行拭子采集 疾病。我们的小组将充当该研究的实验室处理和分析站点。我们将提取 对所有拭子中的 DNA/RNA 进行 SARS-Cov-2 病毒的 qPCR 检测。这将使我们能够 确定 SARS-Cov-2 在美国人口中的发病率以及儿童和儿童之间的差异 成人以及患有哮喘和其他肺部疾病的人。其次，我们将对来自 鼻拭子以确定宿主上皮细胞和免疫细胞对 SARS-Cov-2 感染的反应， COVID-19 呼吸道疾病。这些数据还将使我们能够识别 SARS-Cov-2 病毒的不同毒株 在美国传播、其地理分布以及这些菌株与 COVID-19 疾病严重程度的关系。