Notice of Special Interest (NOSI) regarding the Availability of Urgent Competitive Revisions and Administrative Supplements for Research on Coronavirus Disease 2019 (COVID-19) in Individuals with Down Syndrome for the INCLUDE Project

Application or LOI Due Date
First Available Due Date: July 13, 2020. Expiration Date: July 13, 2021
Brief Description


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.


The Investigation of Co-occurring conditions across the Lifespan to Understand Down syndromE (INCLUDE) Project was developed in response to Fiscal Year 2018 and 2019 Consolidated Appropriations Acts, which encouraged the NIH to expand its current efforts on Down syndrome and common co-occurring conditions also seen in the general population while increasing the pipeline of Down syndromeinvestigators. Information about projects that were funded in 2018 and 2019, as well as the INCLUDE Project Research Plan, is available on the INCLUDE Project website.

Individuals with Down syndrome face significant and changing health challenges but have often been excluded from participation in research that could improve their health outcomes and quality of life. This population is understudied even though Down syndrome is the most common genetic cause of intellectual and developmental disabilities (IDD) and, in the past 25 years, the average lifespan has doubled from 30 to 60 years. In addition to intellectual disability, Down syndrome is associate with an increased prevalence of autism and epilepsy. About 75% of individuals with Down syndrome experience cognitive decline in a syndrome that resembles Alzheimer’s disease, but with onset a decade or two earlier than typical Alzheimer’s disease. Individuals with Down syndrome also have high rates of congenital heart defects, sleep apnea, pulmonary hypertension, obesity, gastrointestinal malformations, thyroid disease, diabetes, leukemia, and other autoimmune or immune dysregulation disorders.

The leading causes of mortality in individuals with Down syndrome are pneumonias, respiratory failure, and dementia. In particular, given that many interferon receptor genes map to chromosome 21, and people with Down syndrome have three copies of chromosome 21, the result is a hyperactive immune system with elevated levels of inflammatory markers that results in a baseline “cytokine storm” status that may predispose them to infection with viruses such as SARS-CoV-2, increasing their risk of severe respiratory tract involvement, respiratory failure and mortality from this virus. In addition, they may be at increased risk of contracting COVID-19 due to residence in congregate housing settings and may experience more severe illness and death given the increased mortality due to the infection in those with IDD. They also have potential to experience health disparities related to access to diagnostic testing, treatment, and interventions. Understanding this unique combination of risk factors will inform testing and treatment for those with Down syndrome who may contract COVID-19 infection.

Research Objectives

In order to rapidly improve our understanding of SARS-CoV-2 and COVID-19 infection, NIH is encouraging the submission of applications for administrative supplements and urgent competitive revisions to active NIH grants to address the pathology, prevention, diagnosis, sequelae, or treatment of COVID-19 in people with Down syndrome. This funding opportunity is intended to support applications that focus on immediate needs to help address the COVID-19 pandemic in a timely manner.

Applications should address whether ongoing or potential future public health restrictions (e.g., closures, physical distancing) might affect the research approach, and if so, include a plan to prevent or mitigate any effect on the proposed study.

General Objectives (relevant to more than one Institute or Center (IC) at NIH):

  • Relationships of individual factors, including co-existing conditions and medications, to resilient or adverse outcomes to SARS-CoV-2 exposure in individuals with Down syndrome.
  • Studies in pre-hospital, emergency, or critical care settings to improve screening, risk stratification, diagnostic testing, care delivery decisions, resource allocation, and clinical outcomes for those with Down syndrome exposed to SARS-CoV-2.
  • Studies of prevention practices (hand washing, effectively covering a cough, social distancing, etc.) and factors that influence adherence, including individual and age differences and social network effects for populations with cognitive impairment such as Down syndrome.
  • Evaluation of pharmacological or health care delivery intervention strategies in those with Down syndrome after exposure to SARS-CoV-2 to prevent or mitigate morbidity and/or improve post-infection health and function.
  • Evaluating strategies used by health systems to reallocate resources, rapidly train practitioners, communicate preventative practices, and maintain adherence to public health and clinical guidelines, with a particular interest in those that serve high-risk groups (e.g., group homes, nursing homes) and resulting racial, ethnic, or regional disparities in access/care.
  • Leveraging longitudinal studies to elucidate how COVID-19-related changes in the social, economic, institutional, and policy environments differentially impact the health and welfare of people across the life course and in vulnerable social groups, such as those with Down syndrome; comparative studies of regional and national approaches are encouraged.

Areas of specific interest by participating Institutes, Centers, and Offices include, but are not limited to, the following:

National Cancer Institute (NCI):

  • To better understand the impact of SARS-CoV-2 infection and its impact on disease progression, response to therapy, care delivery, or survivorship in infants and children with Down syndrome and co-occurring cancer, such as leukemia.
  • Of particular interest are studies that take advantage of unique cancer model systems or analytical tools to study the consequences of SARS-CoV-2 infection and COVID-19 disease progression. Supported research is expected to inform future efforts to diagnose, prevent, mitigate, or treat this viral infection in children with Down syndrome who have leukemia or transient myeloproliferative disorder (or pre-cancer), undergoing treatment for cancer, or are in remission.