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Article Dans Une Revue Journal of Clinical Medicine Année : 2022

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

Laure-Alix Clerbaux
Maria Cristina Albertini
Núria Amigó
Anna Beronius
Gillina Bezemer
  • Fonction : Auteur
Sandra Coecke
  • Fonction : Auteur
Evangelos Daskalopoulos
  • Fonction : Auteur
Giusy del Giudice
  • Fonction : Auteur
Dario Greco
Alberto Mantovani
  • Fonction : Auteur
Amalia Muñoz
  • Fonction : Auteur
Elma Omeragic
Nikolaos Parissis
Mauro Petrillo
Laura Saarimäki
  • Fonction : Auteur
Helena Soares
Kristie Sullivan
  • Fonction : Auteur
Brigitte Landesmann
  • Fonction : Auteur

Résumé

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 (age, sex, genetic factors, lipid disorders, heart failure, gut dysbiosis, diet, vitamin D deficiency, air pollution and exposure to chemicals) influence COVID-19 by applying the Adverse Outcome Pathway (AOP), which is well-established in regulatory toxicology. This framework aims to model the sequence of 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 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 those 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.

Dates et versions

hal-04459491 , version 1 (15-02-2024)

Identifiants

Citer

Laure-Alix Clerbaux, Maria Cristina Albertini, Núria Amigó, Anna Beronius, Gillina Bezemer, et al.. Factors Modulating COVID-19: A Mechanistic Understanding Based on the Adverse Outcome Pathway Framework. Journal of Clinical Medicine, 2022, 11 (15), pp.4464. ⟨10.3390/jcm11154464⟩. ⟨hal-04459491⟩
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