# Mechanisms of Immune Dysfunction in Oral Post-Acute Sequelae of Covid-19

> **NIH NIH R56** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2023 · $581,037

## Abstract

Abstract
Coronavirus disease 2019 (Covid-19) is a viral infection caused by severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2), infecting non-vaccinated and vaccinated people. Covid-19 clinically affects
multiple organs including oral mucosa where SARS-CoV-2 replication occurs to deposit virion into saliva in
sufficient copies (>1000) to be detected. Public health data reveals Covid-19 and periodontitis disproportionally
affects Non-Hispanic Blacks (NHB) and Hispanics (H). We hypothesize that periodontal disease (PD) pre-
conditions oral mucosa for persistent oral pathology and oral Post-Acute Sequelae of Covid-19 (PASC).
However, the cellular and molecular mechanisms underlying this relationship between Covid-19 and poor oral
health outcomes are unclear. Extending our preliminary dataset of oral examination, and immune assessment
of Black and Hispanic cohort, our Aim 1 involves a comparative analysis of the impact of vaccination on oral
PASC indicators and perturbation in oral immune surveillance. We assessed this relationship before vaccination
was available, which provides an opportunity to compare how periodontal health, Covid-19 infection, and the
vaccination status affects minority population (NHB/H) versus Non-Hispanic White (NHW) with similar variables
and risk for oral PASC. Saliva and gingival crevicular fluid (GCF) will be examined to perform comprehensive
profiling of immune cells (both myeloid and lymphoid compartments) and assess mediators of immune cell
activation, polarization and exhaustion contributing to impaired oral immunity. We will decipher three important
gaps of knowledge in an underserved cohort: (1) whether infectivity of SARS-CoV-2 is affected by poor oral
health?, (2) does Covid-19-induced inflammation worsen pre-existing periodontal health, and (3) does Covid-19
vaccination lessen oral PASC viz. periodontal inflammation? In Aim 2, we will examine whether previous
intracellular periopathogens enhance risk for continual reinfection of SARS-CoV-2 and promote oral PASC. Our
lab has optimized an in vitro infection model of SARS-CoV-2 in primary gingival epithelial cells (GEC) to dissect
the role of periodontal pathogens (both bacteria and herpesviruses) enhancing viral tropism and replication.
Characterizing periodontal microbe-SARS-CoV-2 interaction will unravel novel mechanisms that can be targeted
to mitigate oral PASC. Our findings will support that periodontal pathogens increase host susceptibility to SARS-
CoV-2 infection by providing a conducive microenvironment for viral tropism, and persistence. Next, we will
decipher SARS-CoV-2-mediated mechanisms of impairing periodontal immunity. To this end, we will
characterize the novel role of SARS-CoV-2- open reading frames (ORFs) in modulating oral antiviral and
antibacterial immunity by examining viral entry and replication, expression of Pathogen Recognition Receptor
(PRR) and downstream signaling activation. Successful outcomes of this study will disclose no...

## Key facts

- **NIH application ID:** 10892624
- **Project number:** 1R56DE033249-01
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Afsar Raza Naqvi
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $581,037
- **Award type:** 1
- **Project period:** 2023-09-13 → 2025-09-12

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10892624

## Citation

> US National Institutes of Health, RePORTER application 10892624, Mechanisms of Immune Dysfunction in Oral Post-Acute Sequelae of Covid-19 (1R56DE033249-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10892624. Licensed CC0.

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