# Synergistic effects of silica exposure, virus infection and genetic predisposition in systemic autoimmunity

> **NIH NIH R01** · SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE · 2021 · $423,965

## Abstract

Project Summary
COVID-19 caused by the novel coronavirus SARS-Cov-2 first emerged in December 2019 and was officially
declared a pandemic by WHO in March 2020. During this time, COVID-19 has caused millions of cases and
deaths across the world. While most cases are asymptomatic or present with mild respiratory and flu-like
symptoms, a significant fraction of COVID-19 patients develop severe pulmonary complications,
overproduction of inflammatory factors and other manifestations, leading in critical cases to multiorgan
dysfunction, respiratory failure and death. Strikingly, recent evidence indicates that, besides the typical
severe lung pathology, SARS-Cov-2 infection also promotes autoantibody production and other autoimmune
manifestations in some patients. However, why other patients seem protected and the mechanisms for
COVID-19-associated autoimmunity remain unknown. We hypothesize that autoimmunity development in
SARS-Cov-2-infected patients depends on genetic predisposition but also on the history of the individual’s
exposure to environmental triggers, including crystalline silica, an abundant mineral often associated with
autoimmunity. To test this possibility, in this supplemental application we propose experiments with mice
expressing human ACE2, the receptor for SARS-Cov-2. These mice will be infected with SARS-Cov-2 at
doses that induce low-level COVID-related pathology but no mortality, allowing long-term monitoring for
autoimmunity. We will test the effect of the time of SARS-Cov-2 infection and airway exposure to crystalline
silica on autoimmune manifestations in hACE2-expressing non-autoimmune and lupus-prone mouse models.
In addition, we will examine how the dose of silica affects induction of autoimmunity in SARS-Cov-2-infected
mice. The results will provide proof of concept that exposure to environmental agents may exacerbate
COVID-19-associated inflammatory and autoimmune responses, creating the foundation for future studies to
assess the effect of other environmental triggers, mechanisms of disease pathogenesis, and potential
therapeutic interventions.

## Key facts

- **NIH application ID:** 10401216
- **Project number:** 3R01ES031082-02S1
- **Recipient organization:** SAN DIEGO BIOMEDICAL RESEARCH INSTITUTE
- **Principal Investigator:** ROBERTO G BACCALA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $423,965
- **Award type:** 3
- **Project period:** 2021-08-27 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401216

## Citation

> US National Institutes of Health, RePORTER application 10401216, Synergistic effects of silica exposure, virus infection and genetic predisposition in systemic autoimmunity (3R01ES031082-02S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10401216. Licensed CC0.

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