SARS-CoV-2 infection of sustentacular cells disrupts olfactory signaling pathways

Abhishek Kumar Verma; Jian Zheng; David K Meyerholz; Stanley Perlman

doi:10.1172/jci.insight.160277

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SARS-CoV-2 infection of sustentacular cells disrupts olfactory signaling pathways

Journal article

Open access

Peer reviewed

SARS-CoV-2 infection of sustentacular cells disrupts olfactory signaling pathways

Abhishek Kumar Verma, Jian Zheng, David K Meyerholz and Stanley Perlman

JCI insight, Vol.24, e160277

11/15/2022

DOI: 10.1172/jci.insight.160277

PMCID: PMC9869979

PMID: 36378534

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Abstract

Loss of olfactory function has been commonly reported in SARS-CoV-2 infections. Recovery from anosmia is not well understood. Previous studies showed that sustentacular cells, and occasionally olfactory sensory neurons (OSNs) in the olfactory epithelium (OE), are infected in SARS-CoV-2–infected patients and experimental animals. Here, we show that SARS-CoV-2 infection of sustentacular cells induces inflammation characterized by infiltration of myeloid cells to the olfactory epithelium and variably increased expression of proinflammatory cytokines. We observed widespread damage to, and loss of cilia on, OSNs, accompanied by downregulation of olfactory receptors and signal transduction molecules involved in olfaction. A consequence of OSN dysfunction was a reduction in the number of neurons in the olfactory bulb expressing tyrosine hydroxylase, consistent with reduced synaptic input. Resolution of the infection, inflammation, and olfactory dysfunction occurred over 3–4 weeks following infection in most but not all animals. We also observed similar patterns of OE infection and anosmia/hyposmia in mice infected with other human coronaviruses such as SARS-CoV and MERS-CoV. Together, these results define the downstream effects of sustentacular cell infection and provide insight into olfactory dysfunction in COVID-19–associated anosmia.

Details

Title: Subtitle: SARS-CoV-2 infection of sustentacular cells disrupts olfactory signaling pathways
Creators: Abhishek Kumar Verma
Jian Zheng
David K Meyerholz
Stanley Perlman
Resource Type: Journal article
Publication Details: JCI insight, Vol.24, e160277
DOI: 10.1172/jci.insight.160277
PMID: 36378534
PMCID: PMC9869979
NLM abbreviation: JCI Insight
ISSN: 2379-3708
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health, award: PO1 AI060699; DOI: 10.13039/100000002, name: National Institutes of Health, award: RO1 AI129269; DOI: 10.13039/100000002, name: National Institutes of Health, award: RO1 NS36592
Language: English
Date published: 11/15/2022
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9984315740602771

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