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SARS-CoV-2 infection of sustentacular cells disrupts olfactory signaling pathways.
Verma, Abhishek Kumar; Zheng, Jian; Meyerholz, David K; Perlman, Stanley.
  • Verma AK; Department of Microbiology and Immunology, The University of Iowa, Iowa City, United States of America.
  • Zheng J; Department of Microbiology and Immunology, The University of Iowa, Iowa City, United States of America.
  • Meyerholz DK; Department of Pathology, The University of Iowa, Iowa City, United States of America.
  • Perlman S; Department of Microbiology and Immunology, The University of Iowa, Iowa City, United States of America.
JCI Insight ; 2022 Nov 15.
Article in English | MEDLINE | ID: covidwho-2117979
ABSTRACT
Loss of olfactory function has been commonly reported in severe acute respiratory syndrome coronavirus-2 (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.
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Full text: Available Collection: International databases Database: MEDLINE Language: English Year: 2022 Document Type: Article Affiliation country: Jci.insight.160277

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Full text: Available Collection: International databases Database: MEDLINE Language: English Year: 2022 Document Type: Article Affiliation country: Jci.insight.160277