# Project 3: Therapeutic Control of AERD

> **NIH NIH U19** · BRIGHAM AND WOMEN'S HOSPITAL · 2020 · $114,202

## Abstract

PROJECT SUMMARY/ABSTRACT
 SARS-CoV2 requires angiotensin-converting enzyme 2 (ACE2) to bind to host nasal epithelial cells.
However, upon binding of SARS-CoV to ACE2, internalization leads to decreased ACE2 activity. ACE2 can
generate biologically active peptides (Ang(1-9) and Ang(1-7)) which are protective against severe COVID-19-
induced lung injury. Therefore, although ACE2 expression in the nasal epithelium is a required entry point for viral
infection, continued high levels of ACE2 activity may paradoxically provide benefit once the patient is infected. The
host factors that regulate ACE2 expression and activity are not fully known and are missing pieces required to
expand our understanding of the pathogenesis of this disease.
 In March 2020 a French health minister suggested that NSAID use might be associated with more severe
disease presentation in patients with COVID-19. There is now a desperate attempt to understand whether
NSAID use is simply correlated with, or actually causative of, worsened respiratory outcomes. As fever and
myalgias are associated with COVID-19, and both are often treated presumptively with NSAIDs, it is imperative
that we understand the immunological influence of NSAIDs in this disease.
 There is also considerable concern regarding the potential for more severe COVID-19-related respiratory
disease in patients with Type 2 inflammation, and the subset of patients with aspirin-exacerbated respiratory
disease (AERD) have severe upper respiratory inflammation in exactly the anatomic areas of the sinuses
where ACE2 expression has been found to be the highest. It is not yet known how the presence of chronic
Type 2-driven respiratory inflammation affects ACE2 levels in the respiratory tract or the blood.
 We have collected nasal epithelial cells (for mRNA assessment of ACE2 expression), and both nasal fluid
and serum and plasma (for ELISA measurement of the angiotensin-derived peptides as above) which are
banked and are available for immediate analysis. With these, we aim to shed light on two questions that are
plaguing the assessment and treatment of patients with COVID-19:
 1) Does use of NSAIDs increase risk of severe complications from COVID-19?
 2) Are patients with asthma and Type 2 respiratory inflammation at increased risk of severe
 complications from COVID-19?
Completion of these aims would allow us to make recommendations regarding safety of NSAID use in
COVID-19. Many patients are currently choosing to stop their regularly prescribed aspirin and NSAIDs out of
fear, which we suspect is unfounded. We will also further understand whether patients with severe Type 2
respiratory inflammation have different nasal ACE2 expression and angiotensin peptide levels, compared to
healthy controls, which would suggest a differing risk of severe COVID-19 in those patients.

## Key facts

- **NIH application ID:** 10208132
- **Project number:** 3U19AI095219-10S1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Elliot Israel
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $114,202
- **Award type:** 3
- **Project period:** 2020-07-24 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10208132

## Citation

> US National Institutes of Health, RePORTER application 10208132, Project 3: Therapeutic Control of AERD (3U19AI095219-10S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10208132. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*