‘Significant’ drop in MIS-C risk under Omicron: study

Omicron causes far fewer cases of multisystem inflammatory syndrome in children (MIS-C), a new study from Denmark suggests.
 
The syndrome, which is also known as paediatric multisystem inflammatory syndrome – temporally associated with SARS-CoV-2 (PIMS-TS), has affected more than 100 children in Australia since the pandemic began.
 
It is one of the most serious potential manifestations of COVID-19 among children.
 
The Danish research, which was published this week in the American Medical Association’s open access medical journal JAMA Network, also reinforces evidence of vaccination offering significant protection against the illness.
 
The details came out of a prospective, population-based cohort study considering patients aged 0–17 years from across Denmark’s paediatric departments. The research ran from 1 January to 15 March this year.
 
Among 583,618 children and adolescents infected with COVID-19, the researchers identified 12 cases of MIS-C – one from a cohort of 267,086 vaccinated individuals, and 11 among the remaining unvaccinated patients.
 
There were no MIS-C cases among 31,516 estimated individuals with reinfections.
 
The researchers from Aarhus University Hospital state that Omicron was the dominant variant in 95% of cases recorded.
 
According to Philip Britton, Associate Professor of Child and Adolescent Health at the University of Sydney, the study is reassuring.
 
He says the findings reinforce data that emerged earlier in a pre-print study from the UK, which suggested that the condition is less prevalent with Omicron cases than in Delta, which in turn caused fewer cases than Alpha.  
 
‘This should be seen as an encouraging finding for the country,’ Associate Professor Britton told newsGP. ‘It was always reasonably infrequent in the order of one in every 2000 or 3000 infections in children.’
 
The data emerging from Denmark suggests the condition is likely to affect fewer than 1 in 10,000 children in the Omicron wave, even at the higher end of the estimates for unvaccinated patients. 
 
Associate Professor Britton says there is uncertainty over what is causing the lower numbers.
 
However, he notes that existing studies, including the recent one from Denmark, distance themselves from the suggestion that the lower numbers of MIS-C cases are due to population immunity.
 
‘They make the contention that if you exclude the vaccinated group and take the infection rates at a population level, you’re still seeing a reduced frequency of MIS-C, suggesting there’s something Omicron specific,’ he said.
 
There is also ‘plausibility’ to the idea, Associate Professor Britton believes, that the lower rates of complication are virus specific, which he says would be a welcome development.
 
‘In that sense, if we’re going down the Omicron pathway in terms of the future of SARS-CoV-2, that’s good for those who work in child health,’ he said.
 
Associate Professor Britton added there is not enough current evidence to conclude why vaccination seems to confer significant extra protection from the disease.
 
‘It’s not totally clear whether that protective effect is because [the vaccine] protects you from infection,’ he said.  
 
Authors of the Danish study suggest the vaccines’ effect on the immune system is likely to be key among those with breakthrough infections.
 
‘This may be caused by vaccine-induced modulation of the immune system rendering it less prone to cause hyperinflammation after SARS-CoV-2 infection,’ they write.
 
The authors also reported that MIS-C was not observed in reinfections, although acknowledge that only 6% of infected individuals in the study had confirmed reinfection.
 
‘Such a reduced risk after reinfection has not yet been reported,’ they said.
 
For Associate Professor Britton too, no firm conclusions could be drawn from the study about the likelihood of MIS-C in reinfected patients. He also notes one of the limitations of the study is that only a small number of MIS-C cases are involved and said establishing more evidence could be challenging.
 
‘Measuring reinfection rates in populations is difficult,’ he said.
 
‘Because there’s no absolute serological marker of infection or reinfection, you really have to have observed those infections in real time.
 
‘And so the data is reassuring but it would be good to see those sorts of findings from other places as well.’
 
Until relatively recently, there were almost no cases of MIS-C found in Australia due to the low prevalence of COVID-19.
 
Associate Professor Britton says the country has been fortunate to learn from experiences elsewhere and makes the point there have not been any known deaths attributed to MIS-C in Australia to this point.
 
‘Unlike in the early data from overseas, in our experience in Australia it’s a minority of cases that end up in intensive care,’ he said.
 
‘That is probably because we benefited from the early experience from our colleagues overseas in learning how to manage this condition.’
 
Despite the reassuring signs that MIS-C may be less frequent with Omicron, Associate Professor Britton said it is important to remain vigilant given the high existing case numbers.
 
Likewise, while Australia has one of the highest COVID vaccination rates in the world, children aged 5–11 are easily the least protected cohort, with only 39.07% having received two doses at the time of publication.
 
Adolescents aged 12–15 have the second lowest COVID vaccination rate, with only 80% recorded as being fully vaccinated.
 
‘Even though this will be infrequent, we will continue to see cases of this requiring hospital management for the foreseeable future,’ he said.
 
‘GPs may well be the first port of call for families with a child who has got new onset fevers, and then fever along with other features of this [syndrome].
 
‘GPs need to be asking people who come to their practice with persistent fever and any features of [MIS-C] about previous COVID infection as a way of identifying these cases.’
 
Associate Professor Britton said the peak risk period is about 3–5 weeks after SARS-CoV-2 infection.
 
However, he stressed the small risk and the efficacy of existing treatment.
 
‘The general public should be reassured that Australian clinicians are very familiar with this condition now, that we work collaboratively across the country in children’s hospitals to support its management,’ he said.
 
‘And almost all children respond very rapidly to appropriate and early treatment.’
 
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