| Autor: |
Clerbaux, Laure Alix, Albertini, Maria Cristina, Amigó, Núria, Beronius, Anna, Bezemer, Gillina F.G., Coecke, Sandra, Daskalopoulos, Evangelos P., del Giudice, Giusy, Greco, Dario, Grenga, Lucia, Mantovani, Alberto, Muñoz, Amalia, Omeragic, Elma, Parissis, Nikolaos, Petrillo, Mauro, Saarimäki, Laura A., Soares, Helena, Sullivan, Kristie, Landesmann, Brigitte |
| Přispěvatelé: |
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), Centro de Estudos de Doenças Crónicas (CEDOC) |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Popis: |
Funding Information: The work was performed under the JRC Exploratory Research project CIAO—Modelling COVID-19 pathogenesis using the Adverse Outcome Pathway (AOP). Julija Filipovska for her careful reading and valuable inputs. Funding: This research was funded by the Academy of Finland (grand number 322761) for D.G., G.d.G. and L.A.S. and by Fundação para a Ciência e Tecnologia through CEECIND/01049/2020 for H.S. For the other authors, this research received no external funding. 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. publishersversion published |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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