The Evolution from COVID-19 to ARDS

The workshop opened with COVend’s journey of adapting from a COVID-19-focused trial to a broader approach targeting Acute Respiratory Distress Syndrome (ARDS). This pivot exemplified the benefits of understanding drug mechanisms rather than focusing solely on specific pathogens.

Dr. Petra Wülfroth (F4 Pharma) presented FX06 as a platform therapeutic targeting endothelial dysfunction – a mechanism underlying various conditions, including viral infections, septic shock, and reperfusion injury. She emphasised how host-directed therapies can provide universal treatment options, particularly valuable when facing unknown future pathogens.

Bridging Laboratory Research and Clinical Application

Professor Günther Eissner (University College Dublin) demonstrated how mechanistic understanding enhances pandemic preparedness and enables adaptations like those implemented in COVend. His team revealed that FX06 protects endothelial cells by:

• Reducing inflammatory cell migration across blood vessels
• Redistributing key proteins to maintain vascular integrity
• Interfering with pro-inflammatory signaling pathways and angiogenesis

This foundational knowledge allows for more informed trial design and potential therapeutic applications beyond the initial indication.

Clinical Reality Check: Recruitment Challenges

Dr. Michael Nordine (Goethe University Frankfurt) provided candid insights into the clinical challenges faced during patient recruitment. Key learnings included:

• ARDS as a systemic condition and the complexity of ARDS presentation in real-world clinical settings
• The seasonal variation in ARDS cases
• The need to adjust inclusion and exclusion criteria when adapting clinical trials

His experience highlighted that many mild-to-moderate ARDS cases in European clinics go undetected on general wards, representing missed opportunities for intervention.

Panel Discussion: Preparing for Future Challenges

The panel discussion brought together representatives from major European clinical trial networks to address the fundamental question: “What have we learned and what will work better during the next pandemic?”

The Evolving Role of Clinical Trial Networks

Bernard Cholley (ESAIC CTN) opened with a sobering reflection on the healthcare system’s pandemic response: “We learned from the previous pandemic that anesthesiologists are a key component of the healthcare system in such situations because they are able to transform into critical care physicians.“

However, he cautioned about the human cost: “The trauma was deep and we all experienced that many healthcare professionals left the world of intensive care after this episode.”

Balancing Speed with Scientific Understanding

Jacques Demotes (ECRIN) provided crucial insights into the relationship between clinical trials and disease mechanisms: “Clinical trials are mechanism-agnostic.” He explained how the most successful COVID-19 trials were “very pragmatic just addressing the question: is this drug working or not – usually via in-hospital mortality at day 28.” Yet he emphasized the value of biosampling, deeper pathophysiological investigation, and mechanistic studies for pandemic preparedness.

Identifying Core Challenges

Inge Christoffer Olsen (EU SOLIDACT and EU RESPONSE) crystallized the discussion by identifying fundamental obstacles: “We have identified three major hurdles to be overcome when running trials very fast”:

• Regulatory hurdles
• Contractual challenges
• Funding

Sylvia Daamen (ESAIC CTN) added a crucial fourth challenge: “The data sharing blockage between several hospitals due to every country in Europe having their own GDPR settings.”

The Challenge of Pandemic Evolution and Proactive Preparedness Strategies

Inge Christoffer Olsen highlighted a critical lesson about disease evolution: “We started out in the Delta version and then ended up in Omicron, and these are very different situations and diseases.” Thus, understanding pathogenesis is important to adapt clinical research efforts.

Petra Wülfroth offered a forward-thinking perspective: “We don’t have to wait for the next pandemic. We could be active in the meantime.” She proposed studying mechanism-based therapies in current diseases with underlying endothelial inflammation and capillary leak, for example dengue. Inge Christoffer Olsen reinforced this approach: “Being prepared for anything like dengue or Ebola is really important, and ARDS is of course not necessarily pathogen-specific. This work that you’re currently doing is very important in a pandemic preparedness setting.” Nevertheless, setting up clinical trial networks in peace times that can quickly switch into pandemic mode remains crucial.

Institutional Memory and Sustainable Preparedness

Bernard Cholley’s closing remarks captured the delicate balance required: “We have to maintain the competence. We were able to do it. So I think if it’s necessary, we’d probably be doing it again. We have learned some tricks from our experiences on how to transform hospitals into giant ICUs, but it still requires a lot of effort and it is a difficult process.”

The discussion revealed that while the healthcare community demonstrated remarkable adaptability during COVID-19, sustainable preparedness requires addressing systemic challenges in regulation, funding, data sharing, and maintaining institutional knowledge without causing burnout among healthcare professionals. Specifically with regard to ARDS, increasing awareness and more research into host-specific, pathogen-independent therapies will not only increase pandemic preparedness but also reduce the burden on critical care in Europe in normal times.

We extend our sincere thanks to all speakers, panellists and attendees for contributing to this thought-provoking and inspiring exchange.