A 'one size fits all' approach to vaccinating kids aged 5-11yrs?
By Maryanne Demasi, PhD
Last month, US President Joe Biden unveiled the White House plan to roll out COVID-19 vaccines to 28 million children aged 5–11 years. Other politicians joined in the chorus. Australian Health Minister Greg Hunt promised that Aussie kids in this age group could get the jab by the end of the year.
The announcements were made in anticipation of regulatory approval, raising concerns about the enormous political pressure piled upon the drug agencies to green light the vaccines.
Last week, Pfizer submitted a partial application to Australia’s drug regulator (TGA) and will supply the remaining data over the next two weeks. The US is steps ahead.
Last Friday, the FDA granted emergency use authorisation of the Pfizer mRNA vaccine for all children aged 5-11 years, after a unanimous vote (17-0, 1 abstention) by the FDA’s expert advisory panel.
Notably, the meeting roster showed that numerous members of the expert voting panel had conflicts of interest, including those who had received financial grants from Pfizer or who were previous Pfizer employees.
In short: the panel decided that the benefits of the Pfizer vaccine outweighed the harms "based on the totality of scientific evidence available."
Pending the sign-off by the CDC this week, all kids aged 5-11yrs are expected to receive two doses of the vaccine, three weeks apart – each dose will be 10µg, one-third of the adult dose.
FDA deliberation
The vote by panel members was preceded by 8 hours of deliberation - now available to watch on YouTube.
Panel members acknowledged that the risk of severe COVID-19 in children is very low. However, a small proportion will become unwell – most of them with underlying illnesses - and death is “incredibly rare.”
According to US federal data, more than 8,300 kids have been hospitalised and 94 have died out of 1.9 million children aged 5-11 years who have been infected.
Children are considered vectors of the virus and, therefore, can potentially spread the virus to older, vulnerable people. While Pfizer reported 91% efficacy, there is no evidence the vaccine can prevent kids from transmitting the virus to others.
Panel members discussed the ongoing issue of vaccine-induced myocarditis, in which the heart muscle becomes inflamed, but modelling predicted that the risk of myocarditis from COVID-19 infection would be greater.
The debate has been ongoing since a Nordic registry study found that men under the age of 30 who received Moderna (Spikevax) had a slightly higher risk than others of developing myocarditis, sparking a decision in Finland, Sweden, and Norway to suspend the use of the vaccine for young adults and children.
Pfizer said none of the kids in its trials experienced heart inflammation following vaccination, and that using a third of the adult dose (10µg) was likely to curb the effect. Officials remain steadfast that myocarditis and pericarditis cases are “very rare” and “typically mild”.
Members of the public argued that there was not enough safety data since Pfizer only followed the kids for 2 months after the final jab, but experts insisted that US surveillance systems such as VAERS would assist in detecting ongoing issues.
These concerns were unlikely to be assuaged by comments from some of the panel members who appeared to take the approach of "vaccinate now, discover harms later".
“We simply don’t know what the side effects are going to be,” said Dr Cody Meissner, an FDA voting member from Tufts Medical Centre.
“We’re never going to learn about how safe the vaccine is unless we start giving it. And that’s just the way it goes. That’s how we found about rare complications of other vaccines like rotavirus vaccine,” said the temporary voting member Dr Eric Rubin, infectious disease specialist, and current editor-in-chief of the New England Journal of Medicine.
There was one abstention
While a unanimous vote by the FDA advisory committee suggested all members of the panel were onboard with recommending broad use of the vaccine for all children in that age group, the discussion revealed a more divided panel.
There was one member who abstained from voting.
Dr Michael Kurilla (pictured) voiced concerns during the deliberations, and later released in a statement outlining the reasons for his abstention.
His first point was that the trials may have overestimated the level of protection provided by the vaccine. Pfizer only assessed “symptomatic disease” (a sniffle or cough) but did not test kids without symptoms (asymptomatic) which could be up to 50% of kids.
By failing to capture asymptomatic disease, it may have exaggerated the benefit of the vaccine.
Dr Kurilla also raised the issue that 20% of the kids in the trial already had evidence of past infection, (indicated by positive serology testing) suggesting that 1 in 5 kids were already naturally immune.
None of these kids in the trial experienced reinfection, therefore, seriously questioning whether it is necessary to vaccinate this cohort since they already have robust immunity and the benefit-to-harm ratio is unlikely to be favourable.
Dr Kurilla also stated that real world evidence in adults has already shown that two jabs of the Pfizer vaccine, 21 days apart is “suboptimal in terms of durability,” because antibody levels wane after 4-6 months. Dr Kurilla is concerned that this “is likely to be similar in children.”
He also questioned whether, at the lower dose of 10µg in kids, the vaccine would offer the same level of protection against serious hospitalisation seen in adults who receive the higher dose of 30µg. Put simply, the benefit for the prevention of severe disease in most children is still an assumption.
Finally, Dr Kurilla said that while children at high-risk of severe Covid due to underlying conditions would undoubtedly benefit, he did “not expect protection from infection to last more than a few months” and was concerned this would lead to “a negative public perception” of the vaccines.
Kurilla signalled that he would have voted “yes” had the vote allowed for some wriggle room on limiting vaccination to a subset of 5–11-year-olds (highest risk). He resisted voting “no” because that might have also misconstrued his views on the vaccine, so abstention is what he chose in the end.
One-size-fits-all?
This raises relevant criticism of the COVID-19 vaccine rollouts. There has been little room for nuance, policy makers and public health authorities have been selling it as a one-size-fits-all approach.
There is a 100-fold difference in risk between the average 75-year-old versus the average 15-year-old and yet, everyone receives the same treatment. Personalised medicine, case-by-case basis has been thrown out the window in favour of a political and medical overreach.
As Dr Kurilla points out, the panel failed to allow any flexibility in the vote - the question put before the panel was too binary – it was an all-or-nothing approach with no option given to exclude kids with pre-exiting immunity or kids who are healthy with no underlying medical conditions.
Debate continues….
Ultimately, it should be up to parents and guardians to decide to vaccinate their children (unless they are mandated for this age group). Indeed, one of the panel members expressed concern that granting emergency use authorisation may lead to a wave of mandates that would link to school attendance.
The vaccines appear to give children strong “immunogenicity” (antibody immune response) and, according to a report from the Kaiser Family Foundation, about one-third of US parents are eager to vaccinate their 5-to-11-year-old children “right away.”
There is still a vocal group that object to the move based on too many unknowns such as the vaccine’s ability to prevent transmission, the lack of data on serious rare events, or the absence of data on medium and long-term harms.
The CDC suggests that vaccinating all children aged 5 to 11 years would prevent one death in a million. But how many children will be exposed to unnecessary harms to save a life?
These are the difficult questions that will continue to be debated over the coming days and weeks.
One thing is certain, though. The intensity will not simmer down.
This month, Pfizer is expected to apply for FDA approval to vaccinate babies as young as 6 months old.
Further reading
The full FDA briefing document was published here.
Update on Moderna suspension
The FDA has now delayed its assessment of the Moderna vaccine for 12-17 year olds following the decision by the Nordic countries to pause its use due to myocarditis cases.
The use of Pfizer’s vaccine has continued despite concerns it uses the same mRNA technology as Moderna, though some suggest it may have something to do with the different dosing of the two vaccines: Moderna (100µg) and Pfizer (30µg).
The decision has had no bearing on Australian authorities despite the TGA confirming 60 new likely cases of myocarditis in the last week, up to 24 October. Currently, Australian children over the age of 12 years are still being vaccinated with either Moderna or Pfizer mRNA vaccines.