# Investigating Effect of Air pollution and Host Defenses in SARS-CoV2 infection

> **NIH NIH U01** · JOHNS HOPKINS UNIVERSITY · 2020 · $450,313

## Abstract

It is estimated that while the majority of SARS-CoV2 infections in the ongoing coronavirus disease-2019
(COVID-19) pandemic are asymptomatic or have mild symptoms, hospitalizations and mortality largely
occurs in patients with co-morbid conditions such as obesity, diabetes and COPD. Our understanding of
the role of environmental exposures in modifying the response to SARS-CoV2 is emerging and air
pollution; smoking and vaping have been associated with worst outcomes of SARS-CoV2 patients. There is
a time sensitive urgent need to understand host defense mechanisms which are compromised due to
environmental exposures and may increase susceptibility to SARS-CoV2 infection. This competing revision
will forge collaboration with expert in SARS-CoV2 research to expand our horizon in this critical area. We
will test the hypothesis of targeting a host defense pathway which is compromised in air pollution that may
protect and modify the response to SARS-COV2 respiratory infection. Through the parent U grant, we have
demonstrated that chronic exposure to PM2.5 has an overarching role in epigenetic reprogramming. Our
studies have established that transcription factor Nuclear factor erythroid-factor 2 (Nrf2) is a key activator of
anti-oxidative, anti-inflammatory, and innate immune defenses. We and others have demonstrated in
human biospecimens and animal models that chronic exposure to PM2.5 causes a decline in Nrf2 activity
that correlates with compromised innate immune defenses. In mice deficient for Nrf2 (Nrf2-/-), viral and
bacterial infection causes oxidative stress, worsened lung inflammation, acute lung injury and greater
mortality compared to wildtype mice. Genetic or pharmacological activation of Nrf2 pathway can rescue
these effects. Disruption of Nrf2 pathway has been shown to cause upregulation of angiotensin-converting
enzyme 2 (ACE2) which is the functional receptor for SARS-CoV2 entry into lung epithelial cells.
Furthermore, hypomethylation in ACE2 gene has been demonstrated to increase ACE2 expression in
immunocompromised patients. The goal for this project is to investigate the crosstalk of air pollution
exposure, host defense and SARS-CoV2 infection. Preclinical testing of therapeutic efficacy of Nrf2
activators will provide proof of concept for further development a novel drug target for prevention and
treatment of SARS-COV2 infection. The proposal will leverage expertise of our team on air pollution,
respiratory diseases and an expert virologist with ongoing BSL-3 SARS-CoV2 research. Successful
completion of this project will provide proof of concept for future studies directed towards development of a
novel strategy of targeting host defense for prevention and treatment of SARS-CoV2 infection in
susceptible populations.

## Key facts

- **NIH application ID:** 10154690
- **Project number:** 3U01ES026721-04S1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Shyam Biswal
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $450,313
- **Award type:** 3
- **Project period:** 2020-08-26 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10154690

## Citation

> US National Institutes of Health, RePORTER application 10154690, Investigating Effect of Air pollution and Host Defenses in SARS-CoV2 infection (3U01ES026721-04S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10154690. Licensed CC0.

---

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