# Characterizing the Functional Architecture of the Necklace Olfactory System

> **NIH NIH R01** · HARVARD MEDICAL SCHOOL · 2020 · $167,984

## Abstract

Abstract
SARS-CoV-2 (CoV-2) is a pandemic coronavirus that causes the COVID-19 syndrome, which
can include upper respiratory infection (URI) symptoms, severe respiratory distress, acute
cardiac injury and death. Clinical reports suggest that infection with CoV-2 is associated with
high rates of disturbances in smell and taste perception, including anosmia. While many viruses
induce transient changes in odor perception due to inflammatory responses, in at least some
cases COVID-related anosmia has been reported to occur in the absence of significant nasal
inflammation or coryzal symptoms. This observation suggests that CoV-2 might directly target
odor processing mechanisms, although the specific means through which CoV-2 alters odor
perception remains unknown. As part of a paper we recently posted to bioRxiv, we queried both
new and previously published bulk RNA-Seq and scSeq datasets from the olfactory system for
expression of Ace2, Tmprss2 and other genes implicated in coronavirus entry. This analysis
revealed that in mouse and human olfactory epithelium ACE2 transcripts are absent from
olfactory sensory neurons but present in both sustentacular cells and horizonal basal cells. We
performed a similar analysis in mouse olfactory bulb, which revealed that neurons fail to express
Ace2 (either in the olfactory bulb or in the rest of the brain), but that high levels of Ace2
expression are observed in vascular pericytes. These preliminary data suggest that non-
neuronal cell types are the primary target of SARS-CoV2, and represent the likely mechanism
through which the virus causes anosmia. However, these preliminary data are based upon
single cell sequencing, which is biased in terms of the cell types captured, under-represents
gene expression, and fails to identify the distribution of Ace2 protein (which is the relevant
molecule for SARS-CoV-2 entry). Here we request supplementary funding to perform in situ,
immunohistochemistry and single cell sequencing experiments to comprehensively characterize
the expression of Ace2 and other SARS-CoV-2 entry genes in all cell types in the olfactory
system. The results of these experiments will have significant implications for our understanding
of disease mechanisms, and represents a key first step towards developing strategies for
addressing any long-term olfactory-related sequelae of SARS-CoV-2.

## Key facts

- **NIH application ID:** 10151830
- **Project number:** 3R01DC016222-04S1
- **Recipient organization:** HARVARD MEDICAL SCHOOL
- **Principal Investigator:** Sandeep R Datta
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $167,984
- **Award type:** 3
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10151830

## Citation

> US National Institutes of Health, RePORTER application 10151830, Characterizing the Functional Architecture of the Necklace Olfactory System (3R01DC016222-04S1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10151830. Licensed CC0.

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