Identification of olfactory mucosa protein fingerprints in COVID-19

COVID-19 嗅粘膜蛋白指纹识别

基本信息

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
项目类别：
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

项目摘要

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.

项目概要据报道，突然出现的嗅觉障碍是 COVID-19 的早期临床表现之一，尤其是轻症和无症状患者。尽管报告表明嗅觉丧失会在两周后，尚不清楚有多少患者出现持续感染后嗅觉由于缺乏纵向研究而导致功能障碍。嗅神经上皮，位于嗅裂区鼻腔最容易感染 SARS-CoV-2。 SARS-CoV-2 的一种已知受体，血管紧张素转换酶 2 (ACE2) 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嗅觉上皮。我们假设嗅觉上皮细胞中的 SARS-CoV-2 感染产生炎症微环境，进而影响嗅觉感觉功能神经元。嗅粘膜微环境的系统蛋白质组学分析将有助于识别 COVID-19 引起的炎症并提供更好的理解机制嗅觉丧失和恢复。为了确定嗅粘膜蛋白质组学，我们将对嗅裂进行采样在内窥镜引导下鼻拭子区域进行基于TMT的定量质量光谱分析以比较 COVID-19 阳性嗅觉缺失/低嗅觉与非 COVID-19 正常嗅觉科目。我们的目标是 1. 识别 Covid-19 嗅粘膜中不同的蛋白质指纹； 2 执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情况的见解 SARS-CoV-2引发炎症的机制及其对神经元功能的影响。