Time for a paradigm change: understanding COVID-19 disease using next generation innovative, interdisciplinary methodologies

A new JRC study on SARS-CoV-2 examines the existing literature on how this coronavirus enters and infects the human body, exploring how scientists are currently using new innovative technologies based on human biology and mathematics-based methods to better understand the virus and develop new treatments.

It suggests for an integrated, complementary and interdisciplinary use of different experimental model systems and technologies, encouraging further global collaboration and efforts to defeat COVID-19.

The study, published by Chemistry World, represents a global and interdisciplinary collaboration, including cell biologists, clinicians, molecular biologists, toxicologists, computational scientists, and engineers, to develop the knowledge base for novel COVID-19 diagnostic tools, and preventive and curative strategies.

The study will also be included in a reference book on COVID-19 for the global population published by the Royal Society of Chemistry.

The power of an interdisciplinary approach to understand complex human diseases

Human biology is complex and heterogeneous across various ethnic, vulnerable, and susceptible human populations. For a long time, biological research relied on testing on animals to understand the effects on humans. Many studies on the COVID-19 disease also rely on animal studies or large-scale clinical trials. However, animals and humans often respond and react differently to infections.

In vitro methods, using 2 and 3-dimensional cell and tissue-based models, and in silico methods, using mathematical models, can be used as powerful tools to accelerate SARS-CoV-2 studies and discoveries. These models and methods are proven to efficiently mimic a variety of subcellular, cellular, tissue and organ physiological aspects of relevance for the understanding of SARS-CoV-2 related risk factors, vulnerabilities, and potential therapies.

The so-called human mini-brains, a new generation of tissue brain models derived from human stem cell technologies, have been used to mimic the effects of SARS-CoV-2 infection on brain function. As described in this study, they have provided a perspective on how to combine some of these models to mimic COVID-19 brain environment to develop strategies for design and testing of therapeutic interventions and perspectives for using the next generation therapies.

While most of the current treatment strategies focus at the organ or tissue-level, this study also suggests that integrating data generated from innovative and human-based methods at even genetic, molecular, and cellular scale can provide the key scientific knowledge for understanding and taking action regarding SARS-CoV-2 dynamics, effects, and therapeutics (see Figure 1).

A single in vitro or in silico mechanistic method has advantages and limitations; promoting integrated and complementary use of the new generation of scientific cell, tissue and mathematical test methods can provide an interdisciplinary approach to understanding complex human diseases.

New experimental methods and innovative technologies to defeat COVID-19 and other viruses

This JRC study provides also with a panoramic of how different new and innovative methodologies can be integrated hierarchically together. It describes cell, tissue and mathematical based methodologies that are currently helping scientists to analyse how SARS-CoV-2 enters and infects the human body and to come closer understanding infection mechanisms in the diverse human population (children, adults, and elderly people). Some of these methodologies have been used or developed in the context of projects supported by Horizon 2020, the EU research & innovation framework programme for 2014-2020.

These innovative methodologies consist in advanced non-invasive imaging techniques, in vitro 2 and 3 dimensional cell and tissue-based systems, as well as in silico methods performed via computer simulation that can be used as powerful tools to accelerate SARS-CoV-2 studies and discoveries. Encouraging global collaborations can also help in knowledge sharing, inclusion of diverse and large-scale data sets, and accelerate the development of COVID-19 therapeutics. The JRC study shows that integrated and complementary use of diverse different experimental model systems can provide an interdisciplinary approach to an accelerated and more scientific robust and relevant understanding of complex human diseases

The need for changing the paradigm

SARS-CoV-2 is changing its form and function constantly; the recently emerged delta variant is thought to be more transmissible and have higher severity of illness. Thus, in our fight against this virus, we cannot rely only on traditionally used methodologies, which have had a very low translation rate and long timeline to develop therapeutics.

As demonstrated with the COVID-19 case study, the challenge for next generation life science and disease research is not only technological but also cultural. The perspective that sees only animal and clinical studies at the centre of the cognitive process of a disease needs to change; it must include the integration of in silico (the mathematical modelling) and "in vitro (cell and tissue culture research and innovation) methods with all the knowledge streams from the entire biomedical and life science fields.

This paradigm change is even more necessary today, stimulated by the recent European Parliament vote in favour of developing an action plan to end experiments on animals. Members of the European Parliament (MEP) supported a motion for a resolution to accelerate the transition to scientific innovation without the use of animals in research, regulatory testing, and education. This means that MEPs have directed the European Commission to work with scientists, including those from JRC, for a future without any animal testing.

Information technology and artificial intelligence could support a more targeted and rational approach and manage the complexity of the human body processes relatively quickly and at low costs. Greater investment and innovative methodological approaches are needed to accelerate knowledge gathering on SARS-CoV-2 in all the aspects of the disease. To optimise resources and reducing waste and overlap, it is also important to share knowledge on all new methodologies.

Cross-community research on SARS-CoV-2 is essential. The positive effect of the worldwide sharing of scientific knowledge has permitted the rapid understanding of COVID-19 and trying together to combat the spread of the disease and its consequences, lowering the burden of society.

The CIAO project

Complementary to the above new JRC study, in 2020 the JRC has launched - and is continuously facilitating - a hands-on global and interdisciplinary crowdsourcing undertaking called CIAO (Modelling the pathogenesis of COVID-19 using the Adverse Outcome Pathway framework). Scientists from more than 40 research organisations come together, collect and assess available and applicable COVID-19-related knowledge on key biological events involved in various adverse outcomes (AOP) triggered by SARS-CoV-2. Highlighting the individual pathway steps along which COVID-19 progresses will not only point out knowledge gaps for improved research orientation, but also identify biomarkers for better diagnosis and eventually therapy.

Background

The European Commission has been at the forefront of supporting research and innovation and coordinating European and global research efforts, including preparedness for pandemics.

So far, €4.1 billion has been invested from 2007 to 2019 through the 7th Framework Programme and Horizon 2020 in infectious diseases research. In addition to a number of past, and ongoing research actions related to coronaviruses and outbreaks, the Commission also launched several special actions in 2020, as part of a €1 billion pledge for coronavirus research. These actions address epidemiology, preparedness and response to outbreaks, the development of diagnostics, treatments and vaccines, as well as the infrastructures and resources that enable this research. Horizon Europe, the EU research & innovation framework programme for 2021-2027, will continue to invest in research and innovation to tackle infectious diseases including poverty-related and neglected diseases.

The European Commission and EU Member States ministries have also agreed on the first ERAvsCorona action plan, which lays out 10 priority short-term coordinated actions to tackle the coronavirus. The action plan is already delivering results.

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