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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\u2013infected 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\u20134 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\u2013associated anosmia.<\/jats:p>","DOI":"10.1172\/jci.insight.160277","type":"journal-article","created":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T12:00:25Z","timestamp":1668513625000},"source":"Crossref","is-referenced-by-count":76,"title":["SARS-CoV-2 infection of sustentacular cells disrupts olfactory signaling pathways"],"prefix":"10.1172","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6816-2378","authenticated-orcid":true,"given":"Abhishek Kumar","family":"Verma","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0909-128X","authenticated-orcid":true,"given":"Jian","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology 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