Identification of olfactory mucosa protein fingerprints in COVID-19

NIH Pandemic-Era Grants

Pandemic Era Grants

2022

Document text

Principal Investigator: Qizhi  Gong
Organization: UNIVERSITY OF CALIFORNIA AT DAVIS
Fiscal Year: 2022
Award: $196,250
Funding agency: National Institute of Allergy and Infectious Diseases

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.

Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><ACE2><Allergic><Anosmia><Axon><Biological Markers><Body Tissues><Brain><Brain Nervous System><COVID><COVID infected patient><COVID patient><COVID positive patient><COVID-19><COVID-19 infected patient><COVID-19 infection><COVID-19 patient><COVID-19 positive><COVID-19 positive patient><COVID-19 positivity><COVID-19 virus><COVID19><COVID19 infection><COVID19 patient><COVID19 positive><COVID19 positive patient><COVID19 positivity><COVID19 virus><CV-19><CV19><Cell Body><Cells><Clinical><CoV disease><CoV-2><CoV2><Data><Data Set><Dataset><Diagnostic><Dysfunction><Encephalon><Endoscopy><Environment><Evaluation><Exhibits><Foundations><Functional disorder><Future><Glia><Glial Cells><Harvest><Human><Inflammation><Inflammatory><Innate Immune Response><Kolliker's reticulum><Lead><Link><Longitudinal Studies><Mass Photometry/Spectrum Analysis><Mass Spectrometry><Mass Spectroscopy><Mass Spectrum><Mass Spectrum Analyses><Mass Spectrum Analysis><Microbe><Modern Man><Mucosa><Mucosal Inflammation><Mucosal Tissue><Mucositis><Mucous Membrane><Nasal><Nasal Mucosa><Nasal Passages Nose><Nasal cavity><Nerve Cells><Nerve Unit><Neural Cell><Neurocyte><Neuroglia><Neuroglial Cells><Neurons><Non-neuronal cell><Nonneuronal cell><Nose><Olfaction><Olfactory Epithelium><Olfactory Mucosa><Olfactory dysfunction><Patient Self-Report><Patients><Pattern><Pb element><Physiopathology><Protein Fingerprinting><Protein Fingerprints><Proteins><Proteome><Proteomics><Receptor Protein><Recovery><Reporting><Respiratory Epithelium><Respiratory System, Nose, Nasal Passages><Rhinitis><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 infected patient><SARS-CoV-2 infection><SARS-CoV-2 patient><SARS-CoV-2 positive><SARS-CoV-2 positive patient><SARS-CoV-2 positivity><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Sampling><Self-Report><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 infection><Severe acute respiratory syndrome coronavirus 2 positive><Severe acute respiratory syndrome coronavirus 2 positivity><Severe acute respiratory syndrome related corona virus 2><Site><Smell><Smell Perception><Structure of mucous membrane of nose><Structure of respiratory epithelium><Surface><Swab><Testing><Therapeutic><Tissues><Viral><Virus Replication><Wuhan coronavirus><airway epithelium><angiotensin converting enzyme 2><angiotensin converting enzyme II><anosphrasia><anti-microbial><antimicrobial><base><bio-markers><biologic marker><biomarker><cell type><cohort><corona virus disease><corona virus disease 2019><coronavirus disease><coronavirus disease 2019><coronavirus disease 2019 infected patient><coronavirus disease 2019 infection><coronavirus disease 2019 patient><coronavirus disease 2019 positive><coronavirus disease 2019 positive patient><coronavirus disease 2019 positivity><coronavirus disease 2019 virus><coronavirus disease infected patient><coronavirus disease patient><coronavirus disease positive patient><coronavirus disease-19><coronavirus disease-19 patient><coronavirus disease-19 virus><coronavirus infectious disease-19><coronavirus patient><cribriform plate><design><designing><endoscopic imaging><hCoV19><heavy metal Pb><heavy metal lead><infected with COVID-19><infected with COVID19><infected with SARS-CoV-2><infected with SARS-CoV2><infected with coronavirus disease 2019><infected with severe acute respiratory syndrome coronavirus 2><inflammatory environment><inflammatory milieu><insight><long-term study><longitudinal analysis><longitudinal outcome studies><longterm study><loss of smell><nCoV2><nasal swab><nerve cement><neuroepithelium><neuronal><odor perception><olfactory bulb><olfactory impairment><olfactory loss><olfactory perception><olfactory sensory neurons><pathophysiology><patient infected with COVID><patient infected with COVID-19><patient infected with SARS-CoV-2><patient infected with coronavirus disease><patient infected with coronavirus disease 2019><patient infected with severe acute respiratory syndrome coronavirus 2><patient with COVID><patient with COVID-19><patient with COVID19><patient with SARS-CoV-2><patient with coronavirus disease><patient with coronavirus disease 2019><patient with severe acute respiratory distress syndrome coronavirus 2><protein expression><receptor><scRNA-seq><severe acute respiratory syndrome coronavirus 2 infected patient><severe acute respiratory syndrome coronavirus 2 patient><severe acute respiratory syndrome coronavirus 2 positive patient><single cell RNA-seq><single cell RNAseq><single cell expression profiling><single cell transcriptomic profiling><single-cell RNA sequencing><smell test><sustentacular cell><therapeutic agent development><therapeutic development><viral multiplication><viral replication><virus multiplication>