Researchers around the world have intensively investigated the biological mechanisms underlying COVID-19, resulting in a tsunami of data on a daily basis. Relying on a transdisciplinary collaborative effort, the CIAO project aimed to make sense of the scientific knowledge currently available on COVID-19 pathogenesis by using the Adverse Outcome Pathway (AOP) framework.
The AOP framework
An AOP depicts how the disease develops from a Molecular Initiating Event (contact of the SARS-CoV-2 virus with the body) over series of essential and measurable biological Key Events (KE) in cells, tissues, organs toward an Adverse Outcome (AO) such as respiratory distress, multiorgan failure or anosmia.
AOPs are living documents, they can be continuously updated when new information becomes available. AOPs covering a wide variety of adverse outcomes have already been developed and you can find them in the open access aopwiki.org.
Thus, AOPs provide a platform for organizing and consolidating the abundant and fast evolving scientific knowledge on COVID-19 at different biological levels. In addition, it permits to leverage knowledge gained from other fields of research, such as toxicology, to describing the viral disease based on a mechanistic understanding.
Such organization of the knowledge also helps to capture the various modulating factors influencing the clinical outcomes.
Finally, the development of a COVID-19 AOP network highlights shared KEs and spots knowledge gaps. This is particularly interesting for COVID-19 as shared KEs may identify central biological mechanisms involved in multiple adverse outcomes.
The COVID-19 AOP network
The CIAO knowledge community
Building an AOP network modelling COVID-19 pathogenesis relied on interdisciplinary collaborative effort, synergizing exchange between experts from different fields to translate complex biology into messages understandable across disciplines.
Around 70 scientists coming from 40 organisations were participating in the CIAO project (8 April 2020 - 9 February 2023).