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Volume 11
Issue 19
10.3390/cells11193027
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Hypothesis

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

by
Muhammad Ali Shahbaz
1,†,
Francesca De Bernardi
2,†,
Arto Alatalo
1,
Magdalini Sachana
3,
Laure-Alix Clerbaux
4,
Amalia Muñoz
5,
Surat Parvatam
6,
Brigitte Landesmann
4,
Katja M. Kanninen
1 and
Sandra Coecke
4,*
1
A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland
2
Division of Otorhinolaryngology, Department of Biotechnologies and Life Sciences, University of Insubria, Ospedale di Circolo e Fondazione Macchi, 21100 Varese, Italy
3
Environment Health and Safety Division, Environment Directorate, Organisation for Economic Cooperation and Development (OECD), 75775 Paris, France
4
European Commission, Joint Research Centre (JRC), 21027 Ispra, Italy
5
European Commission, Joint Research Centre (JRC), 2440 Geel, Belgium
6
Centre for Predictive Human Model Systems, Atal Incubation Centre-Centre for Cellular and Molecular Biology (AIC-CCMB), Habsiguda, Hyderabad 500039, India
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cells 2022, 11(19), 3027; https://doi.org/10.3390/cells11193027
Submission received: 2 August 2022 / Revised: 9 September 2022 / Accepted: 19 September 2022 / Published: 27 September 2022
(This article belongs to the Special Issue Neurological Symptoms and COVID-19 Pandemic)
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Abstract

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.
Keywords: SARS-CoV-2 infection; COVID-19; anosmia; olfactory neuroepithelium; AOP SARS-CoV-2 infection; COVID-19; anosmia; olfactory neuroepithelium; AOP
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MDPI and ACS Style

Shahbaz, M.A.; De Bernardi, F.; Alatalo, A.; Sachana, M.; Clerbaux, L.-A.; Muñoz, A.; Parvatam, S.; Landesmann, B.; Kanninen, K.M.; Coecke, S. Mechanistic Understanding of the Olfactory Neuroepithelium Involvement Leading to Short-Term Anosmia in COVID-19 Using the Adverse Outcome Pathway Framework. Cells 2022, 11, 3027. https://doi.org/10.3390/cells11193027

AMA Style

Shahbaz MA, De Bernardi F, Alatalo A, Sachana M, Clerbaux L-A, Muñoz A, Parvatam S, Landesmann B, Kanninen KM, Coecke S. Mechanistic Understanding of the Olfactory Neuroepithelium Involvement Leading to Short-Term Anosmia in COVID-19 Using the Adverse Outcome Pathway Framework. Cells. 2022; 11(19):3027. https://doi.org/10.3390/cells11193027

Chicago/Turabian Style

Shahbaz, Muhammad Ali, Francesca De Bernardi, Arto Alatalo, Magdalini Sachana, Laure-Alix Clerbaux, Amalia Muñoz, Surat Parvatam, Brigitte Landesmann, Katja M. Kanninen, and Sandra Coecke. 2022. "Mechanistic Understanding of the Olfactory Neuroepithelium Involvement Leading to Short-Term Anosmia in COVID-19 Using the Adverse Outcome Pathway Framework" Cells 11, no. 19: 3027. https://doi.org/10.3390/cells11193027

APA Style

Shahbaz, M. A., De Bernardi, F., Alatalo, A., Sachana, M., Clerbaux, L.-A., Muñoz, A., Parvatam, S., Landesmann, B., Kanninen, K. M., & Coecke, S. (2022). Mechanistic Understanding of the Olfactory Neuroepithelium Involvement Leading to Short-Term Anosmia in COVID-19 Using the Adverse Outcome Pathway Framework. Cells, 11(19), 3027. https://doi.org/10.3390/cells11193027

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