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 post-infection (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 the 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 to the olfactory epithelium (OE). This AOP-aligned approach allows to identify 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.

SHABHAZ Muhammad Ali;  DE BERNARDI Francesca;  ALATALO Arto;  SACHANA Magdalini;  CLERBAUX Laure-Alix;  MUNOZ-PINEIRO Maria Amalia;  PARVATAM Surat;  LANDESMANN Brigitte;  KANNINEN Katja M.;  COECKE Sandra; 

2022-12-13

Multidisciplinary Digital Publishing Institute (MDPI)

JRC130209

2073-4409 (online),   

https://www.mdpi.com/2073-4409/11/19/3027,    https://publications.jrc.ec.europa.eu/repository/handle/JRC130209,   

10.3390/cells11193027 (online),