The adverse outcome pathway framework applied to neurological symptoms of COVID-19

Lam, A., Ohayon, E., Hogberg, H.T., Shahbaz, M.A., Clerbaux, L.-A., Bal-Price, A., Coecke, S., Concha, R., De Bernardi, F., Edrosa, E., Hargreaves, A.J. ORCID: 0000-0001-9754-5477, Kanninen, K.M., Munoz, A., Pistollato, F., Saravanan, S., Garcia-Reyero, N., Wittwehr, C. and Sachana, M., 2022. The adverse outcome pathway framework applied to neurological symptoms of COVID-19. Cells, 11 (21): 3411. ISSN 2073-4409

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Abstract

Several reports have shown that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential to also be neurotropic. However, the mechanisms by which SARS-CoV-2 induces neurologic injury, including neurological and/or psychological symptoms, remain unclear. In this review, the available knowledge on the neurobiological mechanisms underlying COVID-19 was organized using the AOP framework. Four AOPs leading to neurological adverse outcomes (AO), anosmia, encephalitis, stroke, and seizure, were developed. Biological key events (KEs) identified to induce these AOs included binding to ACE2, blood–brain barrier (BBB) disruption, hypoxia, neuroinflammation, and oxidative stress. The modularity of AOPs allows the construction of AOP networks to visualize core pathways and recognize neuroinflammation and BBB disruption as shared mechanisms. Furthermore, the impact on the neurological AOPs of COVID-19 by modulating and multiscale factors such as age, psychological stress, nutrition, poverty, and food insecurity was discussed. Organizing the existing knowledge along an AOP framework can represent a valuable tool to understand disease mechanisms and identify data gaps and potentially contribute to treatment, and prevention. This AOP-aligned approach also facilitates synergy between experts from different backgrounds, while the fast-evolving and disruptive nature of COVID-19 emphasizes the need for interdisciplinarity and cross-community research.

Item Type:	Journal article
Publication Title:	Cells
Creators:	Lam, A., Ohayon, E., Hogberg, H.T., Shahbaz, M.A., Clerbaux, L.-A., Bal-Price, A., Coecke, S., Concha, R., De Bernardi, F., Edrosa, E., Hargreaves, A.J., Kanninen, K.M., Munoz, A., Pistollato, F., Saravanan, S., Garcia-Reyero, N., Wittwehr, C. and Sachana, M.
Publisher:	MDPI
Date:	28 October 2022
Volume:	11
Number:	21
ISSN:	2073-4409
Identifiers:	Number Type 10.3390/cells11213411 DOI 1782981 Other
Rights:	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/).
Divisions:	Schools > School of Science and Technology
Record created by:	Jonathan Gallacher
Date Added:	20 Jul 2023 08:17
Last Modified:	20 Jul 2023 08:17
URI:	https://irep.ntu.ac.uk/id/eprint/49402

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