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

PROJECT SUMMARYAtopic dermatitis (AD) is the most common chronic inflammatory skin disease in the general population. AD isassociated with defective skin barrier function, microbial and viral dysbiosis, as well as various cutaneousimmune abnormalities including type 2 inflammation and decreased cutaneous host defense. The AtopicDermatitis Research Network-Leadership Center (ADRN-LC) provides that scientific strategy andorganizational 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 ADand 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 casesthat resulted in severe respiratory disease seen predominantly in adults, little information regarding the infectionburden in children is available. This is complicated by the observation that many children experienceasymptomatic infections. Undocumented, and likely infectious, cases could result in exposure to a far greaterproportion of the community than would otherwise occur. Indeed, it has been proposed that undocumented (orsilent) infections are the source for almost 80% of documented infections; thus, it is critical to determine thesilent and symptomatic infection rate in children and to understand why they develop less severe orasymptomatic disease. To overcome challenges for clinical study implementation imposed by currenthealthcare access restrictions, this surveillance study will enroll and prospectively observe eligible children thatare current participants in NIH-funded pediatric research studies and their family members. We will collect nasalswabs from all subjects in 2 week intervals for a 4 month period, again at 6 months, and during respiratoryillnesses. Our group will act as the laboratory processing and analysis site for the study. We will extractDNA/RNA from all swabs and perform a qPCR assay test for the SARS-Cov-2 virus. This will allow us todetermine the incidence of the SARS-Cov-2 in the U.S. population and how it varies between children andadults, and those with asthma and other lung diseases. Secondly, we will perform Dual RNA-seq on RNA fromnasal swabs to determine the host epithelial and immune cell response to infection with SARS-Cov-2 andCOVID-19 respiratory illnesses. This data will also allow us to identify different strains of the SARS-Cov-2 viruscirculating in the U.S., their geographical distribution, and how these strains relate to COVID-19 illness severity.