Abstract

On April 28-29, 2021, 50 scientists from different fields of expertise met for the 3rd online CIAO workshop. The CIAO project “Modelling the Pathogenesis of COVID-19 using the Adverse Outcome Pathway (AOP) framework” aims at building a holistic assembly of the available scientific knowledge on COVID-19 using the AOP framework. An individual AOP depicts the disease progression from the initial contact with the SARS-CoV-2 virus through biological key events (KE) toward an adverse outcome such as respiratory distress, anosmia or multiorgan failure. Assembling the individual AOPs into a network highlights shared KEs as central biological nodes involved in multiple outcomes observed in COVID-19 patients. During the workshop, the KEs and AOPs established so far by the CIAO members were presented and posi­tioned on a timeline of the disease course. Modulating factors influencing the progression and severity of the disease were also addressed as well as factors beyond purely biological phenomena. CIAO relies on an interdisciplinary crowd­sourcing effort, therefore, approaches to expand the CIAO network by widening the crowd and reaching stakeholders were also discussed. To conclude the workshop, it was decided that the AOPs/KEs will be further consolidated, inte­grating virus variants and long COVID when relevant, while an outreach campaign will be launched to broaden the CIAO scientific crowd.

Highlights

  • The CIAO projectCoronavirus disease 2019 (COVID-19) is an ongoing global health emergency

  • Looking forward, the working groups (WG) plans to start publishing the collected knowledge, identify scientific gaps in research, increase the impact by linking collected knowledge to therapeutic interventions, and mapping various factors that can modulate the adverse outcome pathway (AOP) related to the nervous system and that are triggered by SARS-CoV-2 infection

  • At the 3rd CIAO AOP Design Workshop, the developed AOPs and key events (KE) related to COVID-19 and entered into the AOP Wiki were presented and positioned within a timeline of the disease pathogenesis

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Summary

The CIAO project

Coronavirus disease 2019 (COVID-19) is an ongoing global health emergency. Researchers around the world have mobilized to investigate the biological mechanisms of the disease, resulting in a plethora of data being generated daily. AOPs provide a platform for organizing, revising, and consolidating the abundant and fast-evolving scientific knowledge on COVID-19 at different biological levels. They leverage knowledge gained from other fields of research, such as toxicology, to describe the viral disease based on a mechanistic understanding (Kim et al, 2021; Kinaret et al, 2020; Nymark et al, 2021; Vinken, 2013). 19, as the clinical outcomes are disparate, while interconnected KEs may identify central biological mechanisms involved in multiple AOs. Building an AOP network modelling COVID-19 pathogenesis relies on interdisciplinary collaborative effort, synergizing exchange between experts from different fields to translate complex biology into messages understandable across disciplines. Papers on individual aspects of the CIAO project, such as various in-depth AOP descriptions and modulating factors (in blue), a neuro-related pilot literature study, and the multiscale approach (in purple) are foreseen

The CIAO crowd clinicians epidemiologists
Lung AOPs
Systemic inflammation resulting in heart failure
Hub KEs Neuro KEs
Hub KEs Neuro KEs Neuro AOP
The CIAO debate
Findings
Conclusion and next steps
Full Text
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