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