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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MDPI AG
2022-09-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/19/3027 |
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| author | Muhammad Ali Shahbaz Francesca De Bernardi Arto Alatalo Magdalini Sachana Laure-Alix Clerbaux Amalia Muñoz Surat Parvatam Brigitte Landesmann Katja M. Kanninen Sandra Coecke |
| author_facet | Muhammad Ali Shahbaz Francesca De Bernardi Arto Alatalo Magdalini Sachana Laure-Alix Clerbaux Amalia Muñoz Surat Parvatam Brigitte Landesmann Katja M. Kanninen Sandra Coecke |
| author_sort | Muhammad Ali Shahbaz |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T21:53:43Z |
| format | Article |
| id | doaj.art-5278ddfb1ece46dd9b58f995ba99259a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T21:53:43Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-5278ddfb1ece46dd9b58f995ba99259a2023-11-23T20:01:25ZengMDPI AGCells2073-44092022-09-011119302710.3390/cells11193027Mechanistic Understanding of the Olfactory Neuroepithelium Involvement Leading to Short-Term Anosmia in COVID-19 Using the Adverse Outcome Pathway FrameworkMuhammad Ali Shahbaz0Francesca De Bernardi1Arto Alatalo2Magdalini Sachana3Laure-Alix Clerbaux4Amalia Muñoz5Surat Parvatam6Brigitte Landesmann7Katja M. Kanninen8Sandra Coecke9A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, FinlandDivision of Otorhinolaryngology, Department of Biotechnologies and Life Sciences, University of Insubria, Ospedale di Circolo e Fondazione Macchi, 21100 Varese, ItalyA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, FinlandEnvironment Health and Safety Division, Environment Directorate, Organisation for Economic Cooperation and Development (OECD), 75775 Paris, FranceEuropean Commission, Joint Research Centre (JRC), 21027 Ispra, ItalyEuropean Commission, Joint Research Centre (JRC), 2440 Geel, BelgiumCentre for Predictive Human Model Systems, Atal Incubation Centre-Centre for Cellular and Molecular Biology (AIC-CCMB), Habsiguda, Hyderabad 500039, IndiaEuropean Commission, Joint Research Centre (JRC), 21027 Ispra, ItalyA.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, FinlandEuropean Commission, Joint Research Centre (JRC), 21027 Ispra, ItalyLoss 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.https://www.mdpi.com/2073-4409/11/19/3027SARS-CoV-2 infectionCOVID-19anosmiaolfactory neuroepitheliumAOP |
| spellingShingle | Muhammad Ali Shahbaz Francesca De Bernardi Arto Alatalo Magdalini Sachana Laure-Alix Clerbaux Amalia Muñoz Surat Parvatam Brigitte Landesmann Katja M. Kanninen Sandra Coecke Mechanistic Understanding of the Olfactory Neuroepithelium Involvement Leading to Short-Term Anosmia in COVID-19 Using the Adverse Outcome Pathway Framework Cells SARS-CoV-2 infection COVID-19 anosmia olfactory neuroepithelium AOP |
| 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 | SARS-CoV-2 infection COVID-19 anosmia olfactory neuroepithelium AOP |
| url | https://www.mdpi.com/2073-4409/11/19/3027 |
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