Innate immune responses to SARS-CoV-2 infection in the olfactory epithelium

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RESEARCH SUMMARY Sudden-onset of olfactory loss has been recognized as a common COVID-19 symptom. The mechanism of COVID-19 related olfactory dysfunction is unknown. Whether the degree of olfactory deficit is indicative of any long-term neurological diseases in COVID-19 has not been evaluated. Recent single-cell RNA-seq analyses revealed that the receptor for SARS-CoV-2, ACE2, is not expressed by olfactory sensory neurons (OSNs) but are expressed by supporting sustentacular (Sus) cells in the OE. Therefore, Sus cells may be the entry cell type for SARS-CoV-2 in the OE. SARS-CoV-2 infection in the OE needs to be further characterized. Current observations indicate that the viral infection is sparse and localized. Widespread olfactory receptor downregulation has been reported under viral infection suggesting that there might be a distributed viral impact from localized viral infection in the OE. We hypothesize that widespread Sus cell mediated inflammatory response, triggered by SARS-CoV-2, is responsible for COVID-19 associated olfactory loss. In this study, we will characterize inflammatory responses to SARS-CoV-2 in the olfactory epithelium and identify Sus cell specific cytokine expressions; we will established a primary Sus cell culture system to examine viral recognition pathways and transcription factors involved in SARS-CoV-2 induced innate immune responses; we will further determine SARS-CoV-2 infection induced olfactory sensory neuron functional deficits. Through this study, we will gain mechanistic insight into COVID-19 associated olfactory loss.