# Mechanisms of Gastrointestinal COVID-19

> **NIH NIH R56** · WASHINGTON UNIVERSITY · 2022 · $304,049

## Abstract

Project Summary
 Although coronavirus disease 2019 (COVID-19) is primarily defined as a respiratory illness, patients often
experience clinical gastrointestinal symptoms, including abdominal pain and diarrhea. We recently found that
severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, infects and
replicates in human small bowel intestinal epithelial cells (IECs). However, the molecular mechanisms of SARS-
CoV-2 driving gastrointestinal pathology, particularly in vulnerable populations with preexisting diseases remain
unclear.
 In this proposal, our overall objectives are to better define the cellular signaling of SARS-CoV-2 interactions
with IECs, enteric immune responses, and microbiome in the context of health or inflammatory bowel disease
(IBD). Our preliminary data suggest that compared to normal COVID-19 patients, those with IBD have higher
expression of cathepsin L in IECs, which correlated with higher viral loads. Our central hypothesis is that SARS-
CoV-2 induces a distinctive intestinal pathology and mucosal immune response that is shaped by host factors
(IBD), luminal factors (secretions, bile salts, and microbiome), and therapeutics (mesalamine). Specifically, using
healthy and IBD-derived organoids, COVID-19 patient fecal samples, and K18-hACE2 mice, we aim to (1) define
the host factors and cellular mechanisms involved in SARS-CoV-2 infection of normal and IBD epithelium, (2)
determine the impact of intestinal SARS-CoV-2 infection on intestinal immune response and colitis, and (3)
define the environmental factors that influence intestinal infection with SARS-CoV-2.
 With extensive and collaborative expertise in IBD, virology, and host-microbial interactions, we expect to
address mechanistically interesting and clinically important questions like “What is the intestinal pathogenicity of
SARS-CoV-2 and how is it impacted by IBD?”, “What is the interaction of SARS-CoV-2/COVID-19 with intestinal
inflammation and IBD therapies?”, and “What is the impact of intestinal contents and IBD diagnosis/microbiome
on intestinal SARS-CoV-2?”. We anticipate that this pathology will further our understanding of SARS-CoV-2
interactions with the epithelial and immune cells to explain COVID-19 GI symptoms with or without IBD. We also
expect the new information gained from this project will expand our understanding of acute gastrointestinal
pathology and symptoms of COVID-19, provide mechanistic context to existing clinical and translational literature,
and create a foundational knowledge and tool set for deeper investigations into COVID-19 and potentially
pathogenic and emerging coronaviruses of the future.

## Key facts

- **NIH application ID:** 10538795
- **Project number:** 1R56AI167285-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** MATTHEW AARON CIORBA
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $304,049
- **Award type:** 1
- **Project period:** 2022-03-10 → 2022-07-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10538795

## Citation

> US National Institutes of Health, RePORTER application 10538795, Mechanisms of Gastrointestinal COVID-19 (1R56AI167285-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10538795. Licensed CC0.

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