# The UNC Chapel Hill Superfund Research Program (UNC-SRP)

> **NIH NIH P42** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2020 · $464,251

## Abstract

ABSTRACT
This proposal is being submitted as an Emergency Competitive Revision for the University of North Carolina
(UNC) Superfund Research Program (SRP) in the context of the Coronavirus Disease 2019 (COVID-19)
pandemic. We focus on inorganic arsenic (iAs), the #1 contaminant of the Agency for Toxic Substances Registry
(ATSDR) contaminating drinking water around the globe. iAs is toxic to many organs in the body, acting as a
carcinogen, diabetogen, neurotoxicant, and immunosuppressant. Notably, in several of the North Carolina
counties where iAs levels in drinking water are high, the prevalence of severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) infection is also high, indicating that a co-exposure to iAs and SARS-CoV-2 likely
occurs. This co-exposure to iAs on the susceptibility to SARS-CoV-2 infection and COVID-19 severity has never
been studied. The goal of this proposal is to characterize the interaction between iAs exposure and SARS-CoV-
2 infection using differentiated primary human nasal epithelial cells, an established in vitro model for respiratory
infections, and a novel humanized hAS3MT mouse strain, in which the metabolism of iAs and disposition of its
metabolites resemble those in humans. In a strong, transdisciplinary approach, we will use differentiated
primary human nasal epithelial cells and a humanized hAS3MT mice to test the hypothesis that chronic
exposure to iAs enhances susceptibility to SARS-CoV2 infection and severity of COVID-19. While
integrating human and mouse models, we will also examine the role of sex and genetic background on the
disease outcome. The two new additional Aims include: (Aim 1) Identify the effects of iAs and its metabolites on
SARS-CoV-2 infection in differentiated primary human nasal epithelial cells; and (Aim 2) Characterize the effects
of iAs exposure on SARS-CoV-2 MA infection and COVID-19 outcomes in hAS3MT mice. In Aim 1, we test the
hypothesis is that exposure to iAs or its metabolites enhances susceptibility to and severity of SARS-CoV-2
infection in the human nasal epithelial cells. In Aim 2, we will compare immune response, viral titer, lung
pathology and mortality in hAS3MT mice exposed to iAs in drinking water (0, 40, or 400 ppb) and infected with
a mouse-adapted SARS-CoV-2 that has been recently created at UNC Chapel Hill. To assess the role of sex
and genetics, we will use male and female hAS3MT mice with C57BL/6NCrl and 129S6/SvEvTac backgrounds.
The proposed research utilizes novel laboratory models that are available only at UNC and are uniquely suited
for studies of the interaction between environmental iAs exposure and SARS-CoV2 infection. The proposed
research addresses a critical need for understanding of the interaction between a widespread environmental
exposure and a pandemic infection that affects hundreds of millions of people worldwide.

## Key facts

- **NIH application ID:** 10207906
- **Project number:** 3P42ES031007-01S2
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** Rebecca Fry
- **Activity code:** P42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $464,251
- **Award type:** 3
- **Project period:** 2020-09-11 → 2021-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10207906

## Citation

> US National Institutes of Health, RePORTER application 10207906, The UNC Chapel Hill Superfund Research Program (UNC-SRP) (3P42ES031007-01S2). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10207906. Licensed CC0.

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