# Mechanistic Studies of Gut Dysfunction Exacerbation due to SARS-CoV-2 in HIV/SIV infected Individuals

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $396,980

## Abstract

Abstract
 With more than 60 million SARS-CoV-2 -infected patients worldwide and nearly 1.5 million COVID-19-related
deaths recoreded thus far (November 25), the COVID pandemic is one of the most critical global health problem
ever known to humankind, and a major emergency in the US. COVID-19 disproportionately impacts elders or
subjects with pre-existing conditions. Considering that the majority of persons living with HIV and AIDS (PLWHA)
in the US are aged over 50 years and that even the younger PLWHA present with accelerated aging and multiple
comorbidities related to HIV-induced excessive chronic inflammation, it is expected that COVID-19 will be
particularly severe in this risk group. Similar to HIV, SARS-CoV-2 replicates in the gut, and patients with
gastrointestinal symptoms were reported to have a more severe outcome. The exact mechanism through which
SARS-CoV-2 impacts the gut health remains elusive, however it is very likely that the two viruses can potentiate
each other through exacerbation of the gut lesions. Here, we will test the hypothesis that exacerbation of
the gut dysfunction of the SIV-infected PTMs after SARS-CoV-2 superinfection occurs through triggering
excessive mobilization, activation and NETosis of neutrophils at mucosal site and consequent gut
collateral damages. Such a scenario will result not only in an increased risk of the PLWHA to develop more
severe forms of COVID-19, but also to a significant boost of HIV pathogenicity through (i) losing control of HIV
at mucosal sites; (ii) depletion of mucosal and systemic immune effectors; (iii) increases of mucosal and systemic
levels of inflammation; and (iv) enhancement of pre-existent SIV-related comorbidities. This innovative project is
designed to assess pathogenic pathways impacted by SARS-CoV-2 in the gut, to understand the natural history
of COVID-19 related to either triggering or exacerbating HIV-associated gut dysfunction and comorbidities. We
will identify risk factors that could prompt therapy changes in high-risk individuals, such as the PLWH. Our highly
translational project addresses key scientific questions identified as critical by the NIDDK, thus being highly
responsive to RFA 20-021.

## Key facts

- **NIH application ID:** 10452676
- **Project number:** 5R01DK130481-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Ivona Vasile Pandrea
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $396,980
- **Award type:** 5
- **Project period:** 2021-07-17 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10452676

## Citation

> US National Institutes of Health, RePORTER application 10452676, Mechanistic Studies of Gut Dysfunction Exacerbation due to SARS-CoV-2 in HIV/SIV infected Individuals (5R01DK130481-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10452676. Licensed CC0.

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