‘Important’ link between paediatric inflammatory syndromes and COVID-19

Evelyn Lewin

12/05/2020 4:15:24 PM

Australian researchers have been commissioned to investigate the mystery illness, following the death of at least three children in the US.

Sick child
Kawasaki disease historically occurs in children aged between six months and five years, but there have been recent reports of affected teens.


According to The Age, Australian Chief Medical Officer Professor Brendan Murphy has requested a report on the potential link between COVID-19 and Kawasaki disease (KD), which causes many symptoms similar to those recently observed in dozens of children overseas.
Professor Murphy has reportedly asked Australia’s leading paediatric experts to compile the information ahead of Friday’s national cabinet meeting in order to brief Prime Minister Scott Morrison and various state and territory leaders.
Viral immunologist Dr Angus Stock told newsGP the link between Kawasaki disease (KD) and COVID-19 is ‘still an open question’, but definitely possible.

The Walter and Eliza Hall Institute researcher, whose work is dedicated to immunotherapies for KD, said many of the ‘cardinal features’ of the disease are also present in some children infected with COVID-19.
‘It’s very difficult to be definitive about KD and COVID-19, but it looks like many of the symptoms the children are presenting with overlap with what you’d typically see with KD – prolonged fever and, most notably, developing inflammation of the heart,’ he said.
‘On the flipside, some of the symptoms don’t really match up with what we typically see in KD; for instance, abdominal pain.
‘But it certainly is possible.’
Dr Stock is not surprised by reports of increased incidence of KD during the current pandemic, as KD is historically thought to be triggered by a respiratory infection and often a viral infection.
He is also aware of the increase in what has been referred to internationally as a ‘multi-system inflammatory syndrome’ during the pandemic. Dr Stock believes some of those cases may fall directly into the category of KD, while others might not strictly meet the criteria but will be similar in terms of effect and long-term risks.
‘It’s probably going to be a spectrum of disorders within this current syndrome,’ he said.
‘And certainly KD is a systemic vasculitis so you will see multi-organ involvement, fever, rash [and] heart disease.
‘But there is overlap.’
Dr Craig Sable, a US paediatric cardiologist at the Children’s National Hospital in Washington, echoed this sentiment when he spoke to The Washington Post.
‘There are almost no other conditions that cause the type of coronary findings,’ he said.
‘That’s when the global community said there has to be an overlap between this condition and Kawasaki disease.’
One surprising element of KD presentations during the pandemic relates to the age of those affected, according to Dr Stock. Historically, he said, KD occurs in children aged between six months and five years.
‘But we’re seeing a lot more teens presenting with these symptoms, including older children as well,’ he said.
Dr Stock is keen to note the overall risk of children developing such inflammatory conditions associated with COVID-19 remains ‘incredibly small’.
That is partly due to the low case numbers of SARS-CoV-2 infection in Australia, and partly because development of KD relies on two factors.
‘There’s an infection trigger – such as what we’re seeing here – and there’s also a strong genetic predisposition,’ Dr Stock said.
‘So just because you get the infection does not guarantee that you’re going to get these multi-syndrome effects.
‘It’s probably going to affect only a very small fraction of children.’
For this reason, Dr Stock is not concerned about the risks to Australian children as they return to the classroom.
‘The risk is still pretty small, so I don’t think that’s a risk factor in determining whether schools reopen or stay shut,’ he said.
‘This is potentially an additional trigger [but] the risk is still incredibly small and not something you’d factor into that decision.’

Dr Angus Stock said Kawasaki disease is thought to be triggered by a respiratory infection, so it is ‘certainly possible’ to be linked to SARS-CoV-2.

Growing reports linking multi-system inflammatory syndromes such as KD have been emerging internationally during the pandemic.
A case study, published in Hospital Pediatrics in late April, detailed the development of KD in a six-month-old, full term, previously healthy, fully immunised female who screened positive for COVID-19 after developing fever, blotchy rash and minimal respiratory symptoms.
The authors of that paper state that, to their knowledge, this is the ‘first described case of KD with concurrent COVID-19 infection’.
Concern regarding the link between an inflammatory multi-system disorder and COVID-19 strengthened after the New York State Department of Health announced 15 cases between 17 April and 1 May.
Those cases were described as being ‘multi-system inflammatory syndrome’ in children, characterised by persistent fever and features of KD and/or toxic shock syndrome (TSS). Most tested positive for SARS-CoV-2.
New York health officials began issuing alerts on 4 May describing patients aged two to 15 with inflammation in multiple organ systems and features of KD.
As of 10 May, 73 suspected paediatric clinical cases compatible with multi-system inflammatory syndrome associated with COVID-19 have been reported in children in New York. The majority of patients with that syndrome tested positive for SARS-CoV-2.
Three children in New York have died from inflammatory complications possibly linked to COVID-19.
Meanwhile, doctors in the UK have also reported increases in inflammatory syndromes during the pandemic.
A correspondence published in The Lancet on 7 May reported that during a period of 10 days in mid-April, an ‘unprecedented cluster of eight children with hyperinflammatory shock, showing features similar to atypical Kawasaki disease, Kawasaki disease shock syndrome or toxic shock syndrome’ occurred in south-east England.
Most of the children had no significant respiratory involvement.
‘We suggest that this clinical picture represents a new phenomenon affecting previously asymptomatic children with SARS-CoV-2 infection manifesting as a hyperinflammatory syndrome with multi-organ involvement similar to Kawasaki disease shock syndrome,’ the authors wrote.
None of the children initially tested positive for SARS-CoV-2.
One week after the correspondence was submitted, however, it was reported that the Evelina London Children’s Hospital paediatric intensive care unit had managed ‘more than 20 children with similar clinical presentation, the first 10 of whom tested positive for antibody – including the original eight children in the cohort described above’.
Despite the relatively low numbers of COVID-19 cases in Australia, Dr Stock believes it is still important for GPs to be aware of the possible association between the virus and KD to ensure rapid medical care if required.
‘The promptness with which you treat KD is an important determinant in the outcome,’ Dr Stock said.
‘In a very small fraction of children, they will develop coronary artery abnormalities.’
That includes coronary aneurysms that can progress into coronary stenosis and thus pose a risk of subsequent myocardial infarction in a ‘very small fraction’ of children down the track.
‘So it’s critical to evaluate cardiac function in these children,’ he said.
Dr Stock said awareness of the potential association can also aid in rapid diagnosis and therefore treatment for affected children.
‘With KD, the quicker you treat these children with intravenous immunoglobulin, the better the outcome,’ he said.
‘That’s an important message to send.’
According to the Royal Children’s Hospital (RCH), the diagnostic criteria for KD is fever for at least five days, plus four out of the following five criteria:

  • Conjunctivitis (bilateral, dry non-purulent, painless)
  • Lymphadenopathy (cervical, most commonly unilateral, tender; at least one node > 1.5 cm)
  • Rash (polymorphous, no vesicles, bullae or crusts; occurring in first few days; involving trunk and extremities; variable presentation)
  • Lips and oral mucosa involvement (intense hyperaemia of lips and/or diffuse erythema of oropharynx; strawberry tongue)
  • Extremities (hyperaemia and painful oedema of hands and feet progressing to desquamation in convalescent stage; perineal desquamation frequently associated)
KD is the most common cause of acquired heart disease in children in developed countries causing coronary artery aneurysms.
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