The Adverse Outcome Pathway Framework Applied to Neurological Symptoms of COVID-19

SARS-CoV-2 has the potential to also be neurotropic. Many outcomes observed in COVID-19 are associated with the nervous system. However, the mechanisms by which SARS-CoV-2 induces neurologic injury, including neurological and/or psychological symptoms, remains unclear. During the pandemic, the CIAO project “Modelling the Pathogenesis of COVID-19 using the Adverse Outcome Pathway (AOP) framework” was launched with a dedicated Neuro Working Group that aims at organizing the available knowledge on the neurobiological mechanisms underlying COVID-19 using the AOP framework. Biological key events (KEs) were identified including binding to ACE2, blood brain barrier disruption, hypoxia, neuroinflammation and oxidative stress. Scientific evidence was collected to develop four AOPs leading to neurological adverse outcomes: anosmia, encephalitis, stroke, and seizure. The modularity of AOPs allows construction of AOP networks offering a unique visualization of the core pathways and shared mechanisms.The construction of an AOP network for neurological effects in COVID-19 highlights that long-term anosmia occurs following binding of the S protein to ACE2 located in endothelial, neuronal, and glial cells while short term anosmia involves binding to ACE2 found in sustentacular cells of the olfactory epithelium.Neuroinflammation and blood brain barrier disruption emerge as common KEs to many individual AOPs. Some challenges with applying the AOP framework to such a complex disease were identified.

HOGBERG Helena T.;  LAM Ann;  OHAYON Elan;  SHAHBAZ Ali;  CLERBAUX Laure-Alix;  BAL-PRICE Anna;  COECKE Sandra;  CONCHA Rachel;  DE BERNARDI Francesca;  EDROSA Eizleayne;  HARGREAVES Alan;  KANNINEN Katja M.;  MUNOZ-PINEIRO Maria Amalia;  PISTOLLATO Francesca;  SARAVANAN Surat;  GARCIA-REYERO Natàlia;  WITTWEHR Clemens;  SACHANA Magdalini; 

2023-02-08

MDPI

JRC130487

2073-4409 (online),   

https://pubmed.ncbi.nlm.nih.gov/36359807/,    https://publications.jrc.ec.europa.eu/repository/handle/JRC130487,   

10.3390/cells11213411 (online),