System Maintenance Notice

Please note that maintenance work is scheduled between 4 AM and 5 AM - CET. During this time, you may experience reduced performance. Thanks for your patience.

Publications

Journal Article Review Research Support, Non-U.S. Gov't Epublish 13 citations

PubMed: 36359807 DOI: 10.3390/cells11213411

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

Cells 11(21)

Authors: Helena T Hogberg, Ann Lam, Elan Ohayon, Muhammad Ali Shahbaz, Laure-Alix Clerbaux, Anna Bal-Price, Sandra Coecke, Rachel Concha, Francesca De Bernardi, Eizleayne Edrosa, Alan J Hargreaves, Katja M Kanninen, Amalia Munoz, Francesca Pistollato, Surat Saravanan, Natàlia Garcia-Reyero, Clemens Wittwehr, Magdalini Sachana

Affiliations

  • National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27518, USA.
  • Johns Hopkins University, Baltimore, MD 21205, USA.
  • Green Neuroscience Laboratory, Neurolinx Research Institute, San Diego, CA 92111, USA.
  • Physicians Committee for Responsible Medicine, Washington, DC 20016, USA.
  • Institute for Green & Open Sciences, Toronto, ON M6J 2J4, Canada.
  • A.I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland.
  • European Commission, Joint Research Centre (JRC), 21027 Ispra, Italy.
  • Division of Otorhinolaryngology, Department of Biotechnologies and Life Sciences, University of Insubria, Ospedale di Circolo e Fondazione Macchi, 21100 Varese, Italy.
  • School of Science and Technology, Nottingham Trent University, Nottingham NG11 8NS, UK.
  • European Commission, Joint Research Centre (JRC), 2440 Geel, Belgium.
  • Centre for Predictive Human Model Systems Atal Incubation Centre-Centre for Cellular and Molecular Biology, Hyderabad 500039, India.
  • Environmental Laboratory, US Army Engineer Research & Development Center, Vicksburg, MS 39180, USA.
  • Environment Health and Safety Division, Environment Directorate, Organisation for Economic Cooperation and Development (OECD), 75016 Paris, France.

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.

MeSH

Stroke, Signs And Symptoms, Stress, Physiological, Encephalitis, Cells, Blood-Brain Barrier, Adverse Outcome Pathways, Covid-19, Sars-Cov-2

Cited by