The Pandemic Preparedness that Saved Thousands of Lives in ICU
For almost a decade, Professor Alistair Nichol quietly planned and oversaw a curious, annual drill at St Vincent’s University Hospital (SVUH). He and his team would simulate a ‘dry run’ of gathering data about critically ill patients in a pandemic.
“Every year we would dust down this system and the team would put it through its paces. Then we would put it back to sleep again,” says Professor Nichol, Chair of Critical Care Medicine in UCD School of Medicine, who leads the Irish Critical Care-Clinical Trials Network (ICC-CTN). “And I was the guy with the tinfoil hat, leading the exercise.”
But then COVID-19 arrived, and the ‘peace-time’ preparation quickly paid dividends. Teams within the ICC-CTN hit the ground running, harmonising COVID-19 pandemic research in ICUs in Ireland as part of an international network that forged new, evidence-based standards of care and saved thousands of lives in the process.
In 2021, the ICC-CTN won the UCD Research Impact Case Study Competition for its report on ‘Improving outcomes of critically ill patients with COVID-19’, and Professor Nichol received a special commendation from the Irish Research Council for his ‘exceptional contribution’ in the field of medical research, notably in the global response to the COVID-19 pandemic. “It was an overnight success that we had worked on for 12 years,” he says.
Lost opportunity leads to change
The origins of that ‘overnight success’ lay in the H1N1 or swine flu pandemic of 2009. Professor Nichol, a native of Belfast, was training in intensive care medicine in Australia at the time and was part of the research effort there. But without an existing harmonised international system to collect and analyse data from patients with H1N1, it was not possible to mobilise large-scale research in ICUs before that pandemic eased.
“We felt we missed an opportunity with H1N1, and that globally in critical-care medicine we would need to be better prepared next time”, says Professor Nichol.
“So across a network in Ireland, the UK, Canada, Europe and Australia we developed a common approach for data collection and analysis that could be quickly adapted to a pandemic situation. That project became part of a larger, more ambitious EU-funded program of research, PREPARE, the Platform for European Preparedness Against (Re-)emerging Epidemics.”
Their initial, non-pandemic target was community-acquired pneumonia, which is a relatively common problem in ICU, and the consortium put the structures in place to pivot when a pandemic arose.
Then, when the new coronavirus burst onto the scene in 2020, the PREPARE machine swung into action, studying critically ill patients with COVID-19 around the world, including in 18 hospitals in Ireland that were co-ordinated through the UCD Clinical Research Centre at SVUH.
“With H1N1, globally in critical-care medicine we managed to recruit around 100 patients for clinical studies,” says Professor Nichol. “Today, more than 700,000 COVID-19 patients across more than 1,600 hospitals in more than 60 countries have been involved in the observational studies and over 12,000 patients in the interventional clinical trials, in over 350 hospitals in 32 countries carried out by this consortium.”
Genes and medicines
As well as capturing important information about patients’ journeys through critical care with COVID-19, PREPARE is identifying better ways of supporting and treating patients with the condition in ICU.
One avenue is through genetic analysis, explains Professor Nichol. “People had been asking for 20 years if patient genetics can be used to identify risk in ICU, but you typically had patients presenting in ICU with different problems – maybe they had been hit by a bus or they had a serious operation or an infection,” he says. “Now in the pandemic we were seeing almost everyone coming to ICU with the same illness – COVID-19 – and this offered an environment to explore the potential impact of patient genetics.”
The ICC-CTN led in Ireland on the Genetics Of Mortality In Critical Care project spearheaded by Professor Ken Baillie in the University of Edinburgh, and the consortium published their findings in the prestigious journal Nature.
“We were able to show there were some genetic markers linked with a higher risk of death,” says Professor Nichol. “We could also use genetic markers of the inflammatory response in COVID-19 to point to existing medications that could target the disease.”
That went hand in glove with another strand of PREPARE – the REMAP-CAP clinical trial that to date has evaluated 11 drug regimes to treat patients with COVID-19 in ICU.
“We were able to show that some treatments that were being widely suggested for use, like Kaletra [a HIV medication] or convalescent plasma did not work in general for ICU patients, and that some treatments could even be harmful,” says Professor Nichol. “
And we showed that some treatments worked well, for example we saw that steroids combined with a drug that blocks an immune molecule in the body called IL-6 improves COVID-19 outcomes in ICU, with a 10 per cent reduction in death. That has become a standard of care globally, saving thousands of lives.
The two years so far of the COVID-19 pandemic have been ‘truly awful’ and an enormous challenge for healthcare staff, says Professor Nichol, who like many of his colleagues in emergency medicine self-isolated from family and friends to help protect them from the virus.
But now that the success and impact of this global initiative is becoming apparent, it is a good juncture for them to reflect, he adds.
“We had been preparing for so long, when the pandemic hit we leaned into it, it was crisis mode, there was an amazing spirit of collegiality and we wanted to have as big an impact on patient outcomes as we could,” he says. “We got funding from Health Research Board, which was pivotal for us escalating at the time of the pandemic, and we are indebted to the patients and their families for their willingness to participate in research during a hugely challenging time for everyone. We are humbled by the results it has produced, and the impact on society as a whole.”
The work continues
The ICC-CTN Pandemic program may have transformed how research is carried out in the ICU, but this is just the start, says Professor Nichol. “There are many more questions to answer with COVID-19, and we will see patients in ICU with this disease for years to come,” he says. “We are also continuing to refine our preparedness plans in ICU for influenza, to be prepared for future crises. Because pandemics will be around for a long time yet.”
Professor Nicholl was in conversation with Dr Claire O’Connell, BSc Hons (1992), PhD (1998), journalist with the Irish Times and Silicon Republic and Irish Science Writer of the Year 2016.