Children’s risk of long COVID ‘substantially lower’ than expected

As Australia moves towards reopening its borders while the Delta variant continues to spread, concerns are growing over the risks posed to children in the absence of an approved vaccine for anyone younger than 12.
 
But a new review led by the Murdoch Children’s Research Institute (MCRI) is helping to allay some fears, suggesting that long COVID may not be as prevalent as previously thought.
 
Published in The Pediatric Infectious Disease Journal, researchers analysed 14 international studies involving 19,426 children and adolescents who reported persistent symptoms after testing positive to COVID-19.
 
They found the prevalence of long COVID symptoms varied considerably between studies, from 4–66%, and there was also a large variation in the reported frequency of persistent symptoms.
 
What researchers did note, however, is that there is little evidence that symptoms persist longer than 12 weeks, suggesting long COVID may be less of a concern among younger cohorts.
 
Leader of MCRI’s Infectious Diseases Research Group, Nigel Curtis is a Professor of Paediatric Infectious Disease at the University of Melbourne and Head of Infectious Diseases at the Royal Children’s Hospital.
 
He told newsGP the review’s findings should be reassuring for parents and carers.
 
‘We’ve seen so many different figures bandied around, and we’re aware that parents and even children have been quite worried by some of the very high figures that have been in the media,’ Professor Curtis said.
 
‘We were disappointed to find that all the studies had severe, significant limitations and, in general, many were very likely to overestimate the risk.
 
‘So from that point of view, [the new review] is reassuring.’
 
Between 4–12-weeks following acute infection, the most common reported symptoms were headache, fatigue, sleep disturbance, concentration difficulties and abdominal pain. Increasing age, female sex, and allergic diseases or worse pre-infection physical and mental health correlated with persisting symptoms.
 
Meanwhile, Professor Curtis said the absence of a control group in the majority of studies in the review added to the difficulty in distinguishing long COVID symptoms from those associated with the pandemic due to school closures or witnessing the hospitalisation or death of a loved one.
 
‘The five studies that have included a control group, in two of those they didn’t find a difference between the prevalence of those symptoms in those who had and had not had SARS-CoV-2 infection, which really highlights the point,’ he said.
 
The largest study, which included a control group, is the CLoCk study led by researchers from University College London and Public Health England in the UK. It found roughly one in seven children aged 11–17 who had tested positive to COVID-19 in January–March had symptoms 15 weeks later.
 
However, a clear limitation is that the study only had a 13% response rate, suggesting a bias.
 
Why are children less prone to severe disease?
The MCRI’s review confirmed that most COVID infections among children and adolescents remain asymptomatic or mild. However, children with pre-existing health conditions, such as obesity, chronic kidney disease, cardiovascular disease and immune disorders, have a 25-fold increased risk of developing severe disease.
 
As of 19 September, 24% of all COVID-19 cases in Australia have been among those aged 0–19, with no deaths reported in children younger than 10.
 
But why do children, for the most part, appear to be protected?
 
Professor Curtis, who published a paper on the topic in December, says this is ‘the most intriguing part’ of the SARS-CoV-2 story.
 
While the answer remains unknown, there are two dominant theories, starting with age-related differences with the immune system. 
 
‘The frontline part of your immune system is really important for controlling the initial infection and it seems that for children, who do have a stronger innate immune system, it is a critical part of protecting them initially from getting that high viral load,’ Professor Curtis said.
 
‘The next thing is that probably once they do get infected, they’re less likely to get this cytokine storm that’s associated with severe disease.’
 
Beyond the differences in immune response, experts suspect answers may also lie within the blood vessels and clotting function. As people age, endothelial damage increases, as does susceptibility to excessive coagulation.
 
‘That’s why severity of death goes up so steeply after 70–80,’ Professor Curtis said.
 
‘Although it’s a respiratory virus, a lot of the complications are actually as a result of inflammation of the blood vessels, even in the lungs.’
 
What does this mean for vaccination in under-12s?
The authors of the MCRI study note that understanding of long COVID plays a key role in the risk–benefit equation for policy decisions on COVID vaccines.
 
But the lack of a clear definition of what the syndrome is and the impact of disease severity, duration, age, or virus strain adds to the challenge of assessing the true risk. Compounding this is limited age-related data, variable follow-up times, and the reliance on self- or parent-reported symptoms without lab confirmation.
 
‘Further studies to accurately determine the risk of long COVID are urgently needed,’ the authors wrote.
 
‘These should include rigorous control groups, including children with other infections and those admitted to hospital or intensive care for other reasons.
 
‘Longitudinal cohort studies should include regular testing for SARS-CoV-2 to confirm infection, meticulous capture of symptoms, follow-up times that are both consistent and sufficiently long to account for intermittent symptoms, and recording of pre-existing medical conditions. More research to identify underlying immunological mechanisms of long COVID is also needed.’
 
Professor Curtis says given the risk of long COVID in children appears to be relatively low, the decision to vaccinate under-12s is going to be ‘much more difficult’.
 
‘It comes down to that difficulty of risk–benefit equations in vaccination and ensuring that the harm of the vaccine is definitely less than the harm of the disease,’ he said. ‘Whilst that’s easy for adults because we know the harms of disease are very high, as we’re saying here, the acute disease in children is mild and long COVID is rare, and not a big problem.
 
‘I’m obviously massively in favour of vaccination and, provided we have a safe vaccine, I imagine that one day we will be vaccinating against this because we vaccinate against many things that are relatively mild. But it has to be shown to be very safe before we give it to all the under-12s because the risk of the disease is so low.
 
‘The other thing to point out is that people keep worrying about their kids, but the real worry is obviously COVID in adults. The way to protect adults isn’t to protect adolescents and children; it’s to protect adults – get them vaccinated. That’s the key thing.’
 
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