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Mechanistic Understanding of the Olfactory Neuroepithelium Involvement Leading to Short-Term Anosmia in COVID-19 Using the Adverse Outcome Pathway Framework

Loss of the sense of smell (anosmia) has been included as a COVID-19 symptom by the World Health Organization. The majority of patients recover the sense of smell within a few weeks postinfection (short-term anosmia), while others report persistent anosmia. Several studies have investigated the mech...

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Autores principales: Shahbaz, Muhammad Ali, De Bernardi, Francesca, Alatalo, Arto, Sachana, Magdalini, Clerbaux, Laure-Alix, Muñoz, Amalia, Parvatam, Surat, Landesmann, Brigitte, Kanninen, Katja M., Coecke, Sandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9563945/
https://www.ncbi.nlm.nih.gov/pubmed/36230989
http://dx.doi.org/10.3390/cells11193027
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author Shahbaz, Muhammad Ali
De Bernardi, Francesca
Alatalo, Arto
Sachana, Magdalini
Clerbaux, Laure-Alix
Muñoz, Amalia
Parvatam, Surat
Landesmann, Brigitte
Kanninen, Katja M.
Coecke, Sandra
author_facet Shahbaz, Muhammad Ali
De Bernardi, Francesca
Alatalo, Arto
Sachana, Magdalini
Clerbaux, Laure-Alix
Muñoz, Amalia
Parvatam, Surat
Landesmann, Brigitte
Kanninen, Katja M.
Coecke, Sandra
author_sort Shahbaz, Muhammad Ali
collection PubMed
description Loss of the sense of smell (anosmia) has been included as a COVID-19 symptom by the World Health Organization. The majority of patients recover the sense of smell within a few weeks postinfection (short-term anosmia), while others report persistent anosmia. Several studies have investigated the mechanisms leading to anosmia in COVID-19; however, the evidence is scattered, and the mechanisms remain poorly understood. Based on a comprehensive review of the literature, we aim here to evaluate the current knowledge and uncertainties regarding the mechanisms leading to short-term anosmia following SARS-CoV-2 infection. We applied an adverse outcome pathway (AOP) framework, well established in toxicology, to propose a sequence of measurable key events (KEs) leading to short-term anosmia in COVID-19. Those KEs are (1) SARS-CoV-2 Spike proteins binding to ACE-2 expressed by the sustentacular (SUS) cells in the olfactory epithelium (OE); (2) viral entry into SUS cells; (3) viral replication in the SUS cells; (4) SUS cell death; (5) damage to the olfactory sensory neurons and the olfactory epithelium (OE). This AOP-aligned approach allows for the identification of gaps where more research should be conducted and where therapeutic intervention could act. Finally, this AOP gives a frame to explain several disease features and can be linked to specific factors that lead to interindividual differences in response to SARS-CoV-2 infection.
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spelling pubmed-95639452022-10-15 Mechanistic Understanding of the Olfactory Neuroepithelium Involvement Leading to Short-Term Anosmia in COVID-19 Using the Adverse Outcome Pathway Framework Shahbaz, Muhammad Ali De Bernardi, Francesca Alatalo, Arto Sachana, Magdalini Clerbaux, Laure-Alix Muñoz, Amalia Parvatam, Surat Landesmann, Brigitte Kanninen, Katja M. Coecke, Sandra Cells Hypothesis Loss of the sense of smell (anosmia) has been included as a COVID-19 symptom by the World Health Organization. The majority of patients recover the sense of smell within a few weeks postinfection (short-term anosmia), while others report persistent anosmia. Several studies have investigated the mechanisms leading to anosmia in COVID-19; however, the evidence is scattered, and the mechanisms remain poorly understood. Based on a comprehensive review of the literature, we aim here to evaluate the current knowledge and uncertainties regarding the mechanisms leading to short-term anosmia following SARS-CoV-2 infection. We applied an adverse outcome pathway (AOP) framework, well established in toxicology, to propose a sequence of measurable key events (KEs) leading to short-term anosmia in COVID-19. Those KEs are (1) SARS-CoV-2 Spike proteins binding to ACE-2 expressed by the sustentacular (SUS) cells in the olfactory epithelium (OE); (2) viral entry into SUS cells; (3) viral replication in the SUS cells; (4) SUS cell death; (5) damage to the olfactory sensory neurons and the olfactory epithelium (OE). This AOP-aligned approach allows for the identification of gaps where more research should be conducted and where therapeutic intervention could act. Finally, this AOP gives a frame to explain several disease features and can be linked to specific factors that lead to interindividual differences in response to SARS-CoV-2 infection. MDPI 2022-09-27 /pmc/articles/PMC9563945/ /pubmed/36230989 http://dx.doi.org/10.3390/cells11193027 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Hypothesis
Shahbaz, Muhammad Ali
De Bernardi, Francesca
Alatalo, Arto
Sachana, Magdalini
Clerbaux, Laure-Alix
Muñoz, Amalia
Parvatam, Surat
Landesmann, Brigitte
Kanninen, Katja M.
Coecke, Sandra
Mechanistic Understanding of the Olfactory Neuroepithelium Involvement Leading to Short-Term Anosmia in COVID-19 Using the Adverse Outcome Pathway Framework
title Mechanistic Understanding of the Olfactory Neuroepithelium Involvement Leading to Short-Term Anosmia in COVID-19 Using the Adverse Outcome Pathway Framework
title_full Mechanistic Understanding of the Olfactory Neuroepithelium Involvement Leading to Short-Term Anosmia in COVID-19 Using the Adverse Outcome Pathway Framework
title_fullStr Mechanistic Understanding of the Olfactory Neuroepithelium Involvement Leading to Short-Term Anosmia in COVID-19 Using the Adverse Outcome Pathway Framework
title_full_unstemmed Mechanistic Understanding of the Olfactory Neuroepithelium Involvement Leading to Short-Term Anosmia in COVID-19 Using the Adverse Outcome Pathway Framework
title_short Mechanistic Understanding of the Olfactory Neuroepithelium Involvement Leading to Short-Term Anosmia in COVID-19 Using the Adverse Outcome Pathway Framework
title_sort mechanistic understanding of the olfactory neuroepithelium involvement leading to short-term anosmia in covid-19 using the adverse outcome pathway framework
topic Hypothesis
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9563945/
https://www.ncbi.nlm.nih.gov/pubmed/36230989
http://dx.doi.org/10.3390/cells11193027
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