Identification of olfactory mucosa protein fingerprints in COVID-19

项目摘要 据报道，突然发作的嗅觉障碍是COVID-19的早期临床表现之一， 特别是在轻度和无症状患者中。虽然报告显示嗅觉丧失在 两周后，尚不清楚有多少比例的患者出现持续的感染后嗅觉障碍。 由于缺乏纵向研究而导致功能障碍。嗅神经上皮位于嗅裂区， 鼻腔是SARS-CoV-2感染的主要部位。一种已知的SARS-CoV-2受体，血管紧张素- 转化酶2（ACE 2）在非神经元细胞类型中表达，但在嗅觉感觉神经元中不表达。 人类的嗅觉上皮我们假设SARS-CoV-2在嗅上皮中的感染 产生炎症微环境，进而影响嗅觉感觉功能， 神经元对嗅粘膜微环境的系统蛋白质组学分析将有助于 识别COVID-19诱导的炎症，并更好地了解 嗅觉丧失和恢复。为了确定嗅粘膜蛋白质组学，我们将采样嗅裂 在鼻内镜引导下用鼻拭子进行区域TMT定量肿块 光谱分析以比较COVID-19阳性嗅觉缺失/嗅觉减退与非COVID-19正常嗅觉 科目我们的目标是1。识别Covid-19嗅觉粘膜中不同的蛋白质指纹; 2进行纵向 分析嗅粘膜蛋白质组以预测嗅觉恢复。通过本研究建立的数据将 还有助于识别COVID-19生物标志物，指导治疗策略，并提供对一般 SARS-CoV-2引发炎症的机制及其对神经功能的影响。

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.