# Immune dysregulation mechanisms of persistent post-COVID19 olfactory dysfunction

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2024 · $653,547

## Abstract

PROJECT SUMMARY:
The sudden loss of smell and taste are among the defining features of COVID-19 that set it apart from other
viral respiratory syndromes with an incidence of up to 70% with some SARSCoV2 variants. Importantly, in
some patients smell and taste disturbances persist for longer than 12 months after recovery from COVID-19.
Furthermore, classical anti-inflammatory treatment therapies are ineffective for COVID19 chemosensory
dysfunction. To inform targeted treatments, it is critical to elucidate the specific pathways that lead to persistent
disruption of chemosensory function. Our preliminary data show that persistent COVID19 chemosensory
dysfunction involves persistently disordered neuroepithelial composition and infiltration with immune cells with
features of immunosuppressive macrophages. The dysregulated inflammatory milieu prominently features
linoleic acid metabolites and glioma-associated proteins with direct effect on olfactory stem cell proliferation
and differentiation and olfactory sensory neuron survival. This study will determine how the inflammatory but
steroid-resistant immune cells drive chemosensory dysfunction that plagues patients with persistent COVID19
disruption of smell and taste. In Aim 1 we will define the phenotype of the infiltrating immune cells using both
transcriptional and mediator studies. In Aim 2, we will determine how immune mediators defined in Aim 1
disrupt olfactory stem cell and sensory neuron development and apoptosis trajectories using a mouse in vitro
system and relate these findings to the disordered epithelial composition of subjects with persistent COVID19
chemosensory dysfunction. Thus, we use complementary approaches with molecular tools and cell systems
and samples from carefully phenotyped human subjects. The studies should reveal new potential strategies for
therapeutic development that are based on the novel underlying mechanism that we identified here.

## Key facts

- **NIH application ID:** 10978693
- **Project number:** 1R01DC021425-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Lora Bankova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $653,547
- **Award type:** 1
- **Project period:** 2024-07-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10978693

## Citation

> US National Institutes of Health, RePORTER application 10978693, Immune dysregulation mechanisms of persistent post-COVID19 olfactory dysfunction (1R01DC021425-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10978693. Licensed CC0.

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