Associate feature: The fast-tracked research in Scotland that could help mitigate the effects of COVID-19

Ever since coronavirus began to spread around the world, it was clear that a vaccine was the only real answer to the pandemic.

That may be some way off, however, research is being fast-tracked in Scotland and across the UK to find rapid solutions that could help mitigate the effects of COVID-19.

“There is no doubt that vaccine research which is being conducted in the UK, and across the world, in partnership with academic institutions and with industry is a major plank of the research response. It is moving very fast,” Professor David Crossman, Scotland’s chief scientist and vice chair of the Scottish Government’s COVID-19 advisory group, tells Holyrood.

“But I think despite people’s wish for this to happen quickly – and the headlines we see telling us a vaccine will be available within months, wonderful though that would be – history tells us that they don’t arrive as quickly as this.

“In this situation, our immediate response focuses on protecting patient safety, supporting resilience in the NHS and prioritising COVID-19 research. This is a difficult situation and each of these elements are needed to save lives.

“We’re by and large doing three things right now. We’re doing lockdown; we’re building additional capacity, bringing back healthcare workers from retirement or accelerating the graduation of doctors and nurses from universities, building new hospitals in exhibition centres and so on and so forth; and we’re doing things differently, like telephone triage for GPs.

“And all of those are protecting the NHS. But while growing capacity and doing things differently can endure in the medium and perhaps into the long term, lockdown cannot. So we need research: to advance our scientific knowledge about the virus, discover new ways to understand and treat, and ultimately, save lives.”

There are four main research areas: therapeutics (how to treat people with COVID-19), vaccine delivery (to provide immunity), mechanism of the disease (how and why it affects people in particular ways), and disease surveillance (how it transmits across groups).

Looking at the disease mechanisms will involve experimental medicine, studying people with the disease intensively and gathering information through, for example, blood tests, measurements of pressures to ventilate them or CT and MRI scans.

Through collecting and analysing this data, the answers to important questions may be found – and there are still many unanswered questions.

Crossman says: “We know there’s a virus and we know it gets in through the lungs, but [we don’t know] the mechanism of respiratory failure or the mechanism of the multi-organ collapse that we see on intensive care units.

“We don’t know why men seem to be really quite a lot more susceptible than women. We don’t know, but there seems to be some ethnic variation in susceptibility.

“We don’t know a lot of things about this and of course if we can understand those, we stand a better chance of dealing with it.”

Research lies at the heart of this and it is being carried out in Scotland as part of a UK-wide COVID-19 prioritisation exercise.

Given the extraordinary pressures being faced by the health and care system across the country, this approach ensures the best use of limited resources and capacity to support research across the whole of the UK.

“We have to work at scale, by which I mean undertake a very large number of studies, to get answers quickly and to get clear answers,” Crossman says.

“As I often say, irrespective of COVID, there’s one thing worse than no research and that’s bad research. And we don’t want to do that.”

He adds: “This really is a big team effort. Our research infrastructure in Scotland is very well coordinated through NHS Research Scotland.

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“We also have exceptional expertise in Scotland – respiratory, infectious disease and critical care experts – guiding our approach.

“We in CSO [the Chief Scientist Office] are also in regular contact with our colleagues across the four nations.

“We work together to prioritise the COVID-19 studies which hold the most potential for tackling the challenges we face because there is only a certain amount of capacity in the NHS to do research. We don’t want to waste it. We don’t want to duplicate and so on.

“I wish I could say that I thought that we were close to a wonder drug, but research is complex, it takes time and it needs to be done right.”

The therapeutic research is investigating whether medicines that are already in use for treating other viral illnesses have any efficacy in treating coronavirus and Crossman says there are some “plausible antiviral agents that are being trialled”.

There are three national trials, PRINCIPLE in primary care, RECOVERY in hospitals and REMAP-CAP with critically ill patients in intensive care, as well as a range of other priority studies.

The aim of PRINCIPLE (Platform Randomised Trial of Interventions Against COVID-19 in Older People), which is being run in GP practices with patients aged 50 to 64, is to find out whether selected treatments given to those at higher risk of becoming more ill when they are infected with COVID-19 can help reduce the need for hospitalisation.

The RECOVERY (Randomised Evaluation of COVID Therapy) trial is the fastest growing clinical trial in medical history. It is testing if existing or new drugs can help patients hospitalised with confirmed COVID-19.

The first two therapies to be tested are lopinavir-ritonavir, an HIV drug, and low-dose corticosteroids and the aim is to have data available within three months. This is being led by Oxford University with every health board in Scotland participating.

In intensive care there is REMAP-CAP (Randomised, Embedded, Multi-factorial, Adaptive Platform Trial for Community-Acquired Pneumonia), which was an international trial that already existed to trial potential treatments for community-acquired pneumonia, but which is now looking at coronavirus.

The GenOMICC (Genetics of Susceptibility and Mortality in Critical Care) study is another important study which already existed. It is the largest study of its kind anywhere in the world and is now focused on COVID-19.

Led by Dr Kenneth Baillie in Edinburgh and actively recruiting at over 100 sites worldwide, it looks at the genetics of susceptibility and mortality in critical care by comparing DNA from patients who have been confirmed to have COVID-19 with samples from healthy people.

Also led by Baillie is ISARIC (International Severe Acute Respiratory Infection Consortium), which aims to understand the behaviour and spread of COVID-19 in the UK.

Through collecting samples and data from COVID-19 patients, it is hoped answers can be found to questions such as who is at higher risk of severe illness, what is the best way to diagnose the disease, what is happening in their immune systems to help or harm patients, how drugs behave in people with the infection, how long people are infectious for and from which bodily fluids, and whether people are infected with other viruses such as flu at the same time.

This is a snapshot of some key studies. Because of the scale and urgency of the coronavirus crisis, research is also being approved much more rapidly than would usually be the case, with more funding also being channelled into COVID-19 research by governments, industry, universities and research charities.

At the end of March, the CSO launched a call for research into COVID-19 backed by £5m of funding from the Scottish Government.

This covers five priority areas: improved treatments of the infection and its consequences; development of new surveillance approaches; novel interventions to help prevent infection, particularly in those providing the care; supporting the resilience and mental health of frontline workers; and understanding the long-term health impacts of social distancing and behavioural interventions.

Crossman says they’ve had a “tremendous response” to the call, which closed on 8 April.

“We’ve been more than twice oversubscribed with requests and will be making rapid decisions on those, before the end of April in fact.

“This is good news. It’s another part of the response which looks at immediate need but also long-term health impacts.

“Scotland has a world-leading science base and experts across the country have really stepped up to the plate and we’ll be making some important awards to support these priority areas.”

Of course, there are real practical difficulties in carrying out research at a time when frontline health and social care services are really stretched, but there has been widespread support for the research work, with the CMOs from all four nations encouraging participation in clinical trials and the Scottish Government’s director-general for health, Malcolm Wright, writing to health boards asking them to participate.

Crossman says: “We are really testing Scotland’s research infrastructure like never before, but across Scotland there has been tremendous effort.

“We have a weekly call with the NHS R&D directors, we link in with the other nations and it’s all very coordinated.

“We do need to ensure we keep staff ready to do research, which can be difficult to balance with the frontline response, but these trials are being run as simply as they can to reduce the burden on the NHS, with adaptive designs so further treatments can be added if new promising candidates are identified.

“It is really highlighting the importance of research. The CMO is supportive, the director-general is supportive, and there is an understanding that these national priority clinical trials are really vital to gather reliable evidence. So, there’s a lot going on and a lot of support.

“While this may not be the news of a vaccine that everyone is waiting for, research is absolutely at the heart of this response and I see first-hand the efforts of teams across the country to find solutions.”

This piece was sponsored by NHS Research Scotland.