Identification of olfactory mucosa protein fingerprints in COVID-19

COVID-19 嗅粘膜蛋白指纹识别

• 批准号: 10304071
• 负责人: Qizhi Gong
• 金额: $ 23.55万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10304071
• 关键词: 2019-nCoV; ACE2; Allergic; Anosmia; Axon; Biological Markers; Brain; COVID-19; COVID-19 patient; Clinical; Data; Data Set; Diagnostic; Endoscopy; Environment; Evaluation; Exhibits; Foundations; Future; Harvest; Human; Inflammation; Inflammatory; Innate Immune Response; Lead; Link; Longitudinal Studies; Mass Spectrum Analysis; Microbe; Mucositis; Mucous Membrane; Nasal cavity; Neuroglia; Neurons; Nose; Olfactory Epithelium; Olfactory Mucosa; Olfactory dysfunction; Patient Self-Report; Patients; Pattern; Protein Fingerprints; Proteins; Proteome; Proteomics; Recovery; Reporting; Rhinitis; SARS-CoV-2 infection; SARS-CoV-2 positive; Sampling; Site; Smell Perception; Structure of mucous membrane of nose; Structure of respiratory epithelium; Surface; Swab; Testing; Therapeutic; Tissues; Viral; Virus Replication; airway epithelium; antimicrobial; base; cell type; cohort; coronavirus disease; cribriform plate; design; inflammatory milieu; insight; longitudinal analysis; nasal swab; neuroepithelium; olfactory bulb; olfactory sensory neurons; protein expression; receptor; single-cell RNA sequencing; smell test; sustentacular cell; therapeutic development

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.

项目总结 据报道，突然发作的嗅觉障碍是COVID-19的早期临床表现之一， 尤其是在轻度和无症状的患者中。尽管报告显示嗅觉丧失在 两周后，尚不清楚感染后有多大比例的患者出现持续性嗅觉。 由于缺乏纵向研究而导致的功能障碍。位于嗅裂区的嗅神经上皮细胞 鼻腔，对SARS-CoV-2的感染很敏感。已知的SARS-CoV-2受体血管紧张素-2 转换酶2(ACE2)在非神经细胞类型中表达，但在嗅觉神经元中不表达。 人类的嗅觉上皮。我们推测SARS-CoV-2在嗅上皮中的感染 产生炎性微环境，进而影响嗅觉功能 神经元。嗅黏膜微环境的系统蛋白质组学分析将有助于 鉴定新冠肺炎诱导的炎症反应并提供更好的机制 嗅觉丧失和恢复。为了确定嗅觉粘膜蛋白质组学，我们将对嗅裂进行取样。 鼻内窥镜引导下取鼻拭子进行TMT定量肿块 新冠肺炎无渗/低渗阳性与非新冠肺炎正常对照的光谱分析 研究对象。我们的目标是1.在新冠肺炎嗅觉粘膜中鉴定出明显的蛋白质指纹；2.进行纵向 嗅黏膜蛋白质组分析预测嗅觉恢复。通过这项研究建立的数据将 还有助于识别新冠肺炎生物标志物，指导治疗策略，并提供对一般情况的洞察 SARS-CoV-2致炎机制及其对神经功能的影响