Doctors have identified a group of blood compounds that may help to reveal which children are most at risk of developing a rare but life-threatening immune reaction to coronavirus.
The new syndrome emerged last month after hospitals in London admitted a number of children to intensive care units with symptoms that resembled toxic shock mixed with an inflammatory disorder known as Kawasaki disease.
Hospitals around the world have since reported hundreds of similar cases that many doctors believe are caused by the immune system overreacting to the virus sometimes weeks after infection.
About 100 children in Britain have been treated for the disease. Many have been admitted with a persistent fever, skin rashes, abdominal pain and cold hands or feet. At least two children in the UK have died of the disorder, one of whom was an eight-month-old baby at Plymouth’s Derriford hospital in April.
Researchers at Imperial College London analysed blood from some of the sickest children and found they had high levels of five compounds that can be measured in routine tests. Two of the compounds, ferritin and C-reactive protein or CRP, are common blood markers for inflammation. The others are linked to heart damage and blood clotting, namely troponin, BNP and so-called “D-dimers”.
“We know that these markers are present in the very sick patients and at lower levels in some patients with normal Kawasaki disease,” said Michael Levin, a professor of paediatrics and international child health at Imperial.
“We think they can help us decide which children are at risk of progressing to cardiac failure. Essentially what we’re doing is using the blood markers to try and pick out the children that we need to move from district hospitals to specialist centres and then to intensive care units if needed.”
It will take more research to work out if the markers are reliable. If they are, doctors could potentially identify children most at risk from the condition with a simple blood test.
To investigate further, the researchers have been granted permission from England’s chief medical officer, Prof Chris Whitty, to recruit children into a European-funded trial called Diamonds that was already underway to study inflammatory disorders. Doctors around the UK and in various hospitals in Europe are now collecting blood samples for the study to learn which markers may help them predict the severity of disease and to understand the genetics of the disorder.
“This is a rapidly changing situation and we desperately need to learn how to manage it because we are now seeing quite significant numbers of children being admitted to district hospitals all over the place,” Levin said.
“What we don’t know when we’re seeing a child for the first time, or hearing about them if they’re at another hospital, is which children are going to get better on their own and which are going to progress to having Kawasaki disease and are therefore at risk of getting coronary artery aneurysms, and who are the small number who will progress to multi-organ failure.”
The condition, named paediatric inflammatory multisystem syndrome, resembles a mix of toxic shock and Kawasaki disease, the latter of which overwhelmingly affects children. The disease causes inflammation of the blood vessels and in some cases attacks the heart. The most serious complications are coronary aneurysms which can be fatal when they clot. Doctors typically intervene swiftly with anti-inflammatory drugs or immune-suppressing medicines.
Doctors do not have time to run a formal trial to learn which treatments work best. Instead, plans have been drawn up for an international database they will use to enter anonymous information on children in their care, including blood test results and what treatments are given when. “It’s not as good as a randomised trial, but it’s the next best thing in a pandemic. Because the numbers will be so big, it might give us a signal as to which treatments are best,” Levin said.
Prof Russell Viner, the president of the Royal College of Paediatrics and Child Health, said it was too early to know how beneficial blood biomarkers might be for stratifying children with the new inflammatory disease.
“This peak will tail off as the whole Covid peak tails off and we are already seeing that,” Viner said. “But if Covid is going to be with us for a while, and there’s going to be a rise in Covid cases, we are going to see more of these cases. So we absolutely need ways of identifying early on which children might have this as opposed to a child who just presents with a fever, so biomarkers might be exceptionally helpful in the longer term.”
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