Influence of NSAIDs and AERD on the expression and function of ACE2 - implications for SARS-CoV2 severity

  • Funded by National Institutes of Health (NIH)
  • Total publications:0 publications

Grant number: unknown

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Key facts

  • Disease

    COVID-19
  • Start & end year

    2020
    2021
  • Known Financial Commitments (USD)

    $114,202
  • Funder

    National Institutes of Health (NIH)
  • Principle Investigator

    Pending
  • Research Location

    United States of America, Americas
  • Lead Research Institution

    BRIGHAM AND WOMEN'S HOSPITAL
  • Research Category

    Pathogen: natural history, transmission and diagnostics

  • Research Subcategory

    Pathogen morphology, shedding & natural history

  • Special Interest Tags

    Gender

  • Study Subject

    Clinical

  • Clinical Trial Details

    Not applicable

  • Broad Policy Alignment

    Pending

  • Age Group

    Unspecified

  • Vulnerable Population

    Unspecified

  • Occupations of Interest

    Unspecified

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 cangenerate 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 viralinfection, continued high levels of ACE2 activity may paradoxically provide benefit once the patient is infected. Thehost factors that regulate ACE2 expression and activity are not fully known and are missing pieces required toexpand our understanding of the pathogenesis of this disease. In March 2020 a French health minister suggested that NSAID use might be associated with more severedisease presentation in patients with COVID-19. There is now a desperate attempt to understand whetherNSAID use is simply correlated with, or actually causative of, worsened respiratory outcomes. As fever andmyalgias are associated with COVID-19, and both are often treated presumptively with NSAIDs, it is imperativethat we understand the immunological influence of NSAIDs in this disease. There is also considerable concern regarding the potential for more severe COVID-19-related respiratorydisease in patients with Type 2 inflammation, and the subset of patients with aspirin-exacerbated respiratorydisease (AERD) have severe upper respiratory inflammation in exactly the anatomic areas of the sinuseswhere ACE2 expression has been found to be the highest. It is not yet known how the presence of chronicType 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 fluidand serum and plasma (for ELISA measurement of the angiotensin-derived peptides as above) which arebanked and are available for immediate analysis. With these, we aim to shed light on two questions that areplaguing 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 inCOVID-19. Many patients are currently choosing to stop their regularly prescribed aspirin and NSAIDs out offear, which we suspect is unfounded. We will also further understand whether patients with severe Type 2respiratory inflammation have different nasal ACE2 expression and angiotensin peptide levels, compared tohealthy controls, which would suggest a differing risk of severe COVID-19 in those patients.