# Olfactory and neurological manifestations of acute and post-acute murine COVID-19

> **NIH NIH R01** · UNIVERSITY OF IOWA · 2024 · $656,039

## Abstract

Abstract
SARS-CoV-2, the cause of COVID-19, continues to cause widespread infection and morbidity, but death rates
have decreased as most of the world has either been infected or vaccinated or both. However, at the same time,
it has become clear that many patients have developed long term sequelae. These sequelae, called PASC (Post
Acute Sequelae of COVID-19), affect many organ systems even though virus is found at autopsy in nearly all
studies only in the respiratory and gastrointestinal tracts. One common symptom of acute COVID-19 is anosmia.
Recovery of olfactory function is often incomplete in patients. However, only supporting (sustentacular) cells and
not olfactory sensory neurons are infected in patients, raising the question of how infection of a supporting cell
could have such profound effects on olfaction. In addition, neurological disease is also present in many patients
with PASC. Many of these manifestations reflect ongoing inflammation (usually observed on autopsy), but the
basis of these inflammatory changes is unclear since virus cannot be detected. We have isolated a mouse-
adapted virus that causes severe acute respiratory disease in infected mice, as well as persistent signs of
disease is the lungs and brains months after the acute infection has resolved. Infected mice develop anosmia,
as well as long term behavioral abnormalities and defects in neurotransmitter expression, but virus is not present
in the brain. Our central hypothesis is that ongoing inflammation is a major contributory factor in the observed
dysfunction in the olfactory and neurological systems. This hypothesis will be addressed in the following specific
aims: Specific Aim 1: To understand the relationship between sustentacular cell infection and olfactory
dysfunction and to understand the basis of chronic changes in the brains of SARS-CoV-2-infected mice. Acute
and chronic changes in olfactory pathways will be probed using electrophysiological and olfactory
measurements. These changes will be related to sustentacular function and gene expression. Parts of the brain,
such as the substantia nigra, which are affected in neurodegenerative diseases such as Parkinson’s disease will
be studied. Our preliminary results show changes in neurotransmitter expression in the substantia nigra several
months after infection, supporting this hypothesis. Specific Aim 2: To examine the role of viral macromolecular
products and infiltrating inflammatory cells in the brains of mice infected with SARS-CoV-2 in the development
of PASC. Using molecular and immunological approaches, we will assess whether inflammation results from
extrapulmonary SARS-CoV-2 infection and rapid clearance within the first days of infection (‘hit and run’). Using
a mouse in which infiltrating myeloid cells can be readily identified, we will analyze localization, function and
gene expression of these infiltrating myeloid cells, as well as of T cells that infect the brain chronically. The
ultimate goal is ...

## Key facts

- **NIH application ID:** 10793341
- **Project number:** 2R01AI129269-06
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Stanley Perlman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $656,039
- **Award type:** 2
- **Project period:** 2016-09-23 → 2028-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10793341

## Citation

> US National Institutes of Health, RePORTER application 10793341, Olfactory and neurological manifestations of acute and post-acute murine COVID-19 (2R01AI129269-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10793341. Licensed CC0.

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