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

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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.