Preprint Review Version 1 Preserved in Portico This version is not peer-reviewed

Factors Modulating COVID-19: A Mechanistic Understanding Based on the Adverse Outcome Pathway Framework

Laure-Alix Clerbaux
* ORCID logo ,
Maria Cristina Albertini
ORCID logo ,
Núria Amigó
ORCID logo ,
Anna Beronius
ORCID logo ,
Gillina F.G. Bezemer
,
Sandra Coecke
,
Evangelos P. Daskalopoulos
,
Giusy Del Giudice
,
Dario Greco
ORCID logo ,
Lucia Grenga
ORCID logo ,
Alberto Mantovani
,
Amalia Muñoz
,
Elma Omeragic
ORCID logo ,
Nikolaos Parissis
,
Mauro Petrillo
,
Laura A. Saarimäki
,
Helena Soares
ORCID logo ,
Kristie Sullivan
,
Brigitte Landesmann
Version 1 : Received: 6 June 2022 / Approved: 8 June 2022 / Online: 8 June 2022 (09:47:23 CEST)

A peer-reviewed article of this Preprint also exists.

Clerbaux, L.-A.; Albertini, M.C.; Amigó, N.; Beronius, A.; Bezemer, G.F.G.; Coecke, S.; Daskalopoulos, E.P.; del Giudice, G.; Greco, D.; Grenga, L.; Mantovani, A.; Muñoz, A.; Omeragic, E.; Parissis, N.; Petrillo, M.; Saarimäki, L.A.; Soares, H.; Sullivan, K.; Landesmann, B. Factors Modulating COVID-19: A Mechanistic Understanding Based on the Adverse Outcome Pathway Framework. J. Clin. Med. 2022, 11, 4464. Clerbaux, L.-A.; Albertini, M.C.; Amigó, N.; Beronius, A.; Bezemer, G.F.G.; Coecke, S.; Daskalopoulos, E.P.; del Giudice, G.; Greco, D.; Grenga, L.; Mantovani, A.; Muñoz, A.; Omeragic, E.; Parissis, N.; Petrillo, M.; Saarimäki, L.A.; Soares, H.; Sullivan, K.; Landesmann, B. Factors Modulating COVID-19: A Mechanistic Understanding Based on the Adverse Outcome Pathway Framework. J. Clin. Med. 2022, 11, 4464.

Abstract

Addressing factors modulating COVID-19 is crucial since abundant clinical evidence shows that outcomes are markedly heterogeneous between patients. This requires identifying the factors and understanding how they mechanistically influence COVID-19. Here, we describe how eleven selected factors influence COVID-19 by applying the Adverse Outcome Pathway (AOP) framework well-established in regulatory toxicology. This framework aims to model the sequence of events starting from an initial interaction of a stressor with the organism and the progress through key biological events leading to an adverse health outcome. Several linear AOPs depicting pathways from the binding of the virus to ACE2 up to clinical outcomes observed in COVID-19 patients have been developed and integrated into a network offering a unique overview of the mechanisms underlying the disease. As SARS-CoV-2 infectibility and ACE2 activity are the major starting points and inflammatory response is central in the development of COVID-19, we evaluated how eleven intrinsic and extrinsic factors modulate those processes impacting clinical outcomes. Applying this AOP-aligned approach enables the identification of current knowledge gaps orientating for further research and allows to propose biomarkers to identify of high-risk patients. This approach also facilitates expertise synergy from different disciplines to address public health issues.

Keywords

SARS-CoV-2 infection; COVID-19; modulating factors; Adverse Outcome Pathway; sex; age; co-morbidities; lifestyle; environment; pre-existing conditions

Subject

Medicine and Pharmacology, Pulmonary and Respiratory Medicine

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Cite Share 1
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.