NIH is issuing this Notice of Special Interest (NOSI) to highlight the urgent need for research on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Coronavirus Disease 2019 (COVID-19) in individuals with Down syndrome in conjunction with the INCLUDE (INvestigation of Co-occurring conditions across the Lifespan to Understand Down syndromE) Project. Because many people with Down syndrome are at increased risk of having co-occurring medical conditions, such as pulmonary disease, cardiac problems, obesity, diabetes, sleep apnea, and altered immune function that may predispose them to more severe infection with SARS-CoV-2, they may be particularly vulnerable to COVID-19 complications. Combined with shared living situations, and reduced access to testing and treatment services due to disparities in provision of resources, the impact of COVID-19 infection in people with Down syndrome is likely to be elevated. The overarching goal of this NOSI is to improve understanding and treatment of COVID-19 infection in individuals with Down syndrome and reduce COVID-19 associated morbidity and mortality for this population, which may be disproportionately affected by, have higher infection rates of, and/or be at elevated risk for adverse outcomes from contracting the virus.