# Interferon hyperactivity, COVID19, and Down syndrome

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $619,607

## Abstract

PROJECT SUMMARY.
This is an application for an Urgent Competitive Revision to our Transformative R01 award funded by the NIH
INCLUDE Project and NIAID titled ‘Understanding Down Syndrome as an Interferonopathy’. The central
hypothesis of the parent award is that hyperactivation of interferon (IFN) signaling causes many of the
developmental and clinical hallmarks of DS. In this revision, we will investigate the interplay between IFN
hyperactivity, immune dysregulation, COVID19 pathology, and immunity against SARS-CoV-2. We hypothesize
that IFN hyperactivity will modify the clinical course of COVID19 in DS, including long term immunological
sequalae, while potentially impairing development of cellular and humoral immunity against SARS-CoV-2. Our
Specific Aims are:
1. Determine the clinical and immunological characteristics of COVID19 in DS. It is increasingly evident
that individuals with DS infected by SARS-CoV-2 are more likely to be hospitalized, develop secondary bacterial
infections, and die at younger ages. However, many questions remain unanswered about the clinical course of
COVID19 in DS. What are the risk factors for severe COVID19 in DS? Are there treatment modalities that are
less or more effective in DS? What are the sequalae of SARS-CoV-2 infection in survivors with DS? Here, we
will employ the National COVID Cohort Collaborative (N3C), the DS-Connect® registry, and the Human Trisome
Project (HTP) cohort study to generate a definitive assessment of the clinical and immunological characteristics
of COVID19 in DS. We will complete parallel analyses of the N3C database and data obtained by the HTP team
via electronic health record abstraction and participant surveys to identify differences in early symptoms,
immunological parameters, clinical course, risk factors, response to different treatment modalities, and long term
sequalae, with emphasis on potential differences by age, sex, race/ethnicity, and geography.
2. Investigate the immune phenotype of a cohort of COVID19 survivors with DS. Our extensive investigation
of the immune phenotype of people with DS has revealed strong dysregulation of T and B cell lineages, including
changes that could impair the development of cellular and humoral immunity against SARS-CoV-2 and the
response to SARS-CoV-2 vaccines. Now, supported by the DS-Connect® registry and the HTP cohort study, we
will obtain biospecimens from individuals with DS that survived SARS-CoV-2 infection. We will include these
samples in our ongoing pan-omics characterization of IFN hyperactivity and immune dysregulation in DS, while
also investigating the development and duration of memory T and B cell responses and production of neutralizing
antibodies specific for SARS-CoV-2.
Altogether, these synergistic aims, which address multiple aspects of this NOSI, will advance our understanding
of the impacts of trisomy 21 and IFN hyperactivity on COVID19 in DS, thus informing the rapid development of
customized preventive, diagnostics...

## Key facts

- **NIH application ID:** 10215951
- **Project number:** 3R01AI150305-01S1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Joaquin M. Espinosa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $619,607
- **Award type:** 3
- **Project period:** 2020-09-02 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10215951

## Citation

> US National Institutes of Health, RePORTER application 10215951, Interferon hyperactivity, COVID19, and Down syndrome (3R01AI150305-01S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10215951. Licensed CC0.

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