Researchers at Morriston Hospital have been awarded Welsh Government funding to investigate one of the devastating consequences of Covid-19.
The virus is known to trigger the formation of abnormal blood clots that can lead to damage in organs including the brain and lung, causing life-threatening complications such as stroke.
What is not yet known is why this happens – and that’s what the team at the Welsh Centre for Emergency Medicine Research will investigate should there be an upsurge in cases.
Over the years, its multidisciplinary group of clinical and non-clinical scientists has developed an international reputation in detecting and measuring how acute critical illness alters the clotting of the blood.
It has attracted millions of pounds in research funding and published more than 100 papers, often in prestigious worldwide journals.
Main photo above: The research team. Front row: Professor Adrian Evans, Dr Suresh Pillai; middle row: Dr Matthew Lawrence, Dr Katy Guy; back row: Jan Whitley, Dr Rangaswamy Mothukuri
Now the centre, based in the hospital’s Emergency Department, has been awarded a Welsh Government Sêr Cymru grant to carry out a unique research study in the event of a second wave.
It will involve the use of new biomarkers (a form of blood test) which the team previously developed to screen patients at risk of thromboembolic disease such as stroke, sepsis and deep vein thrombosis.
All these have an inflammatory component, which causes abnormal coagulation.
The biomarker can detect these abnormalities, helping with the diagnosis of the diseases, their progression and severity, as well as monitoring the effectiveness of treatment.
The same principles will underline the Covid-19 study, as the virus has a marked systemic inflammatory element.
This can lead to a localized clotting abnormality in small vessels in organs such as the lung, brain, kidney and heart, especially in patients with a previous history of underlying vascular disease and chronic illness.
Professor Adrian Evans founded and leads the emergency medicine academic research programme at Morriston Hospital.
He said: “Covid-19 can be an aggressive infective disease which has a marked inflammatory component, and which is known to have a major impact on the clotting system.
“We know that it enters through receptors in cells and the surface of blood vessels, triggering abnormal clot formation localised within the affected organ.
“In the lungs it decreases oxygenation, and that’s why patients are so short of oxygen. It also causes abnormal clots to form in the brain, kidney, heart and other organs.
“We know conventional tests can pick this up but they don’t tell us why, or the mechanisms behind it.
“Neither do they give us information on the nature of the abnormal clots’ structure and quality compared to healthy clots.
“We have developed new biomarkers on clot structure which we think will give us more insights into why these mechanisms occur, and how effective the current treatments are.
“We hope to have a better idea of how the effect of COVID-19 and its inflammatory response not only triggers abnormal coagulation, but also to ascertain how drugs such as dexamethasone and anticoagulants such as heparin affect the disease process.
“This is very much a mechanistic study which we hope will give us some idea of what treatment options may potentially be optimised in the future.”
The value of the research is around £130,000, including the Welsh Government grant and match-funding.
As well as Professor Evans, the research team comprises clinical haemorheologist Dr Matthew Lawrence, consultants Dr Suresh Pillai, Dr Katy Guy and Dr Rangaswamy Mothukuri, and research assistant Jan Whitley. A research nurse will also be recruited.
Assuming there is a second wave, patients with suspected Covid-19 will be screened as they arrive at Morriston ED. Those confirmed to have the disease will be followed up over a period of days and weeks.
Some will require standard treatment, such as anticoagulants, anti-inflammatory drugs, steroids, oxygen and intravenous fluids.
They may be well enough to go home after a short period. The condition of other patients, however, will worsen.
These patients may suffer severe breathing difficulties, renal problems or cerebrovascular injury, which may result in them being put on life support in intensive care.
Professor Evans (pictured) said it was believed the clotting abnormalities developed as people became more severely unwell with Covid-19.
“We will measure how the disease progresses and, as it progresses, why it produces abnormal clots in some and not others,” he said.
“We will also look at those groups who get better with treatment. What is different about them? Is it that they are not developing abnormal clots to the same extent – in which case, why?
“Or is it that the treatment is more effective in certain patients and not others – and, again, why?”
The study, likely to involve upwards of 40 patients, will also consider factors such as comorbidities and family history to provide a whole picture.
Some preliminary work has already been carried out, involving four patients who came through ED with Covid.
Professor Evans said that, as a result, the team knew they could use the biomarker to accurately measure the extent it affected blood clotting.
“We are the only centre in the UK or anywhere who can use this specific biomarker of clot microstructure to look at abnormal clotting to discover new insights into the disease,” he said.
“It has been pioneered here at the Welsh Centre for Emergency Medicine Research and Swansea University.
“Ultimately we hope to get a better understanding of why these people develop abnormal clots, to look at what treatments are effective in preventing the clots, and to improve the healthcare of patients in the long term and save lives.”