PROJECT SUMMARY/ABSTRACT: This application is being submitted to PA-20-272 in accordance with NOT-OD-22-137. We propose to leverage the infrastructure of the parent study (R01 AI143710), a large population-based birth cohort of over 3,000 individuals with Down syndrome (DS), an experienced study team, to study all-cause respiratory morbidity during the pandemic time of individuals with DS. This application is eligible for the Administrative Supplement award as it proposes to address “Component 2: Assembly of a large cohort of individuals with Down syndrome across the lifespan to perform deep phenotyping and study co-existing conditions” of the INLCUDE project (Investigation of Co-occurring conditions across the Lifespan to Understand Down syndromE). Individuals with DS will be followed through 2023 to study the respiratory burden during the pandemic, a priority of National Institute of Allergy and Infectious Diseases (NIAID) for the INCLUDE project. The underlying immunologic, anatomic, and physiologic abnormalities of DS make individuals with DS susceptible to respiratory viral infections and less responsive to immunizations. During the pandemic, studies have shown that individuals with DS are at increased risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and more severe SARS-CoV-2 infections. On the other hand, the implementation of non-pharmaceutical interventions (NPIs) such as hand washing, social distancing, and face masking has resulted a dramatic global reduction in the incidence of common respiratory virus infections during the pandemic. Respiratory burden resulting from these viruses in individuals with DS might be reduced. The overarching objectives of the study are to determine the burden of respiratory morbidity in individuals with DS during the pandemic time. Building upon the parent study of a population-based birth cohort of 3,051 children with DS who were born in 1995-2019 and enrolled in Tennessee Medicaid Program and Department of Defense Military Healthcare System, we propose to 1) expand the cohort to include individuals with DS who were born during the pandemic (born 2020-2023, estimated N=705) and 2) extend the follow-up period of the current subjects (born 1995-2019) to 2023 to study all-cause respiratory morbidity during the pandemic time. We will determine the rates and quantify the severity of COVID-19 related and unrelated respiratory healthcare encounters. Respiratory morbidity, including healthcare encounters for COVID-19, pneumonia, otitis media, croup, wheezing, asthma, bronchitis, bronchiolitis, respiratory failure, tympanostomy tube, and other respiratory related morbidity, will be examined. Public Health Impact. Results of the study will provide a better understanding of the overall prevalence and burden of COVID-19 related and unrelated respiratory morbidity, and provide important information to inform the usage of subsequent vaccines, protection products, and therapeutic strategie...