PROJECT SUMMARY A sudden onset of olfactory impairment is reported as one of the early clinical manifestations of COVID-19, particularly among mild and asymptomatic patients. Though reports indicate that olfactory loss resolves within two weeks, it is unknown what proportion of the patients develops persistent postinfectious olfactory dysfunction due to lacking longitudinal studies. Olfactory neuroepithelium, located in the olfactory cleft region of the nasal cavity, is venerable to SARS-CoV-2 infection. A known receptor to SARS-CoV-2, angiotensin- converting enzyme 2 (ACE2) is expressed in the non-neuronal cell types but not olfactory sensory neurons in the human olfactory epithelium. We hypothesize that SARS-CoV-2 infection in the olfactory epithelium produces an inflammatory microenvironment which in turn impacts on the function of olfactory sensory neurons. Systematic proteomics analysis of the olfactory mucosa microenvironment will facilitate the identification of COVID-19 induced inflammation and provide a better understanding of mechanisms in olfactory loss and recovery. To determine olfactory mucosal proteomics, we will sample the olfactory cleft region with nasal swab under the guidance of endoscopy and perform TMT-based quantitative mass spectrometry analysis to compare COVID-19 positive anosmic/hyposmic with non-COVID-19 normosmic subjects. We aim to 1. identify distinct protein fingerprints in Covid-19 olfactory mucosa; 2 perform longitudinal analysis of olfactory mucosa proteomes to predict olfactory recovery. Data established through this study will also help identify COVID-19 biomarkers, guide therapeutic strategies, and provide insight into the general mechanism of SARS-CoV-2 triggered inflammation and its impact on neuronal functions.