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The somewhat mysterious inflammatory syndrome that can arise in children with the coronavirus has been linked to brain damage in severe cases.
The coronavirus is thought to be mild in four out of five cases, with children in particular rarely becoming critically-ill.
Nevertheless, NHS doctors were told to look out for signs of "multi-system inflammation" early in the outbreak, after intensive care units in London saw eight children with unusual symptoms, some of whom tested positive for the coronavirus.
The mysterious inflammation has been likened to atypical Kawasaki disease; a rare condition that usually affects children under five and causes blood vessels to become inflamed, leading to heart complications in around a quarter (25%) of patients.
To better understand the newfound syndrome's complications, medics from Boston Children's Hospital analysed more than 1,600 coronavirus patients aged under 21, of whom just over a third (36%) had multi-system inflammation.
Among those with "neurologic involvement", 88% had passing symptoms, while the remaining 12% developed life-threatening complications, like strokes or an infection of the central nervous system.
While some recovered, just over a quarter (26%) died and two in five (40%) had "new neurologic deficits" when sent home from hospital.
Initially considered a respiratory infection, the coronavirus is now known to affect many parts of the body. The pathogen can impact the brain, evidenced by some patients enduring headaches, dizziness, and a loss of taste or smell.
Watch: Coronavirus can cause inflammatory syndrome in children
The Boston medics analysed coronavirus-positive children – average age nine – who were admitted to 61 hospitals across the US between 15 March and 15 December 2020.
Of the over 1,600 children, just over one in five (22%) had "neurologic involvement" at the time of admission or during their hospital stay; defined as symptoms or disease related to the nervous system.
More than one in five (22%) of these individuals had an underlying neurological disorder.
Overall, more than one in 10 (12%) of those with "neurologic involvement" developed "life-threatening conditions associated with COVID-19 [the disease caused by the coronavirus]".
Of these, 15 had severe encephalopathy; defined as brain disease or damage.
Twelve endured a stroke, while eight had a central nervous system infection or demyelination; damage to the fatty protective covering that surrounds nerves.
Four developed Guillain-Barré syndrome or similar; when the immune system attacks nerves. Four also had acute fulminant cerebral edema; the severe and sudden build-up of fluid around the brain.
The patients with life-threatening neurological complications were found to have skewed immune cell levels and higher amounts of the blood-clotting protein fibrinogen.
Of the patients with "COVID-19–related life-threatening neurologic involvement", 11 (26%) died, while 17 (40%) had "new neurologic deficits at hospital discharge".
"Many children and adolescents hospitalised for COVID-19 or multi-system inflammatory syndrome in children had neurologic involvement, mostly transient symptoms," the medics wrote in the journal JAMA Neurology.
"A range of life-threatening and fatal neurologic conditions associated with COVID-19 infrequently occurred.
"Effects on long-term neurodevelopmental outcomes are unknown."
What we know about the coronavirus-inflammatory syndrome
On 1 May 2020, the UK Royal College of Paediatrics and Child Health defined so-called "paediatric inflammatory multi-system syndrome temporally associated with coronavirus" (PIMS-TS) as a persistent fever, inflammation and "evidence of single or multi-organ dysfunction".
This could occur alongside a positive or negative coronavirus test, providing any other "microbial cause" is ruled out.
While cases of the inflammatory syndrome have spiked during the pandemic, not everyone with the condition swabs positive for the coronavirus. Some have suggested this may be due to false-negative results.
Medics have likened the inflammatory syndrome to Kawasaki disease, which commonly causes a rash, fever, and red hands and feet.
Kawasaki disease is thought to come about when the immune system over-reacts to an infection. Left untreated, the heart complications can be fatal in 2% to 3% of patients.
Scientists from the New York University Grossman School of Medicine have previously noted "significant clinical overlap exists" between Kawasaki and the coronavirus-related inflammatory syndrome.
The latter, however, "has been characterised by more widespread systemic inflammation and higher rates of acute complications, including cardiogenic shock"; when the heart suddenly cannot pump enough blood to meet the body's needs.
The inflammatory disorder has also been likened to toxic shock syndrome (TSS).
Often associated with tampon use, TSS is a medical emergency that can lead to fever, flu-like symptoms, nausea, vomiting and difficulty breathing.
Experts have warned these symptoms are a sign the body is overwhelmed as it tries to fight an infection.
While the inflammatory syndrome may sound alarming, the vast majority of children are said to recover with hospital treatment, with experts repeatedly stressing there is no need to panic.
The Royal College of Paediatrics and Child Health previously advised parents call 999 or take their child to A&E if they:
Become pale, mottled or abnormally cold to touch
Pause in their breathing, have an irregular breathing pattern or grunt
Have severe breathing difficulties, while becoming agitated or unresponsive
Go blue around the lips
Have a seizure
Become extremely distressed, confused, lethargic or unresponsive
Develop a rash that does not disappear with pressure, like when pressed under a glass
Have testicular pain, especially teenagers
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