Covid-19 vaccine successful in youngest children, Moderna says.
A clinical trial of Moderna’s Covid-19 vaccine for children ages 6 months to under 6-years-old achieved its primary goals.
Moderna has announced results from its ongoing clinical trial studying the safety and efficacy of its Covid-19 vaccine in children ages 6 months to under 6 years. While minimal data were provided via the press release published today, enough information was provided to indicate that the long wait for a safe and effective vaccine for the youngest children may soon be over.
Here’s what we know:
1. Moderna's trial was designed to measure antibody levels that vaccines generated among recipients. Before the trial began, it was decided that if antibody levels detected in young children were similar enough to those detected in older people from the earlier trials, the trial would be deemed successful. The rationale for this was that for older people, outcomes like severe disease and hospitalization are more common and therefore easier to measure in trials with thousands of people. The idea is that if young children mounted similar antibody levels as adults—a concept known as immunebridging—protection against long-term consequences including severe disease, hospitalization, and death would be implied. Pfizer has successfully used this strategy in older children, as demonstrated by a handful of observational studies showing that among vaccinated kids, rates of serious complications from Covid-19 were far lower than among similar but unvaccinated kids.
2. The vaccine was reasonably effective in preventing symptomatic Covid-19. Efficacy was 43.7% for children ages 6 months to 2 years, and 37.5% among children ages 2 to under 6 years. While this is lower than the initial adult studies, these findings are not surprising because much of Moderna’s data was collected during the Omicron wave, which we know causes the vaccines to offer less protection against infection. However, the fact that the antibody levels were apparently similar to those seen in earlier trials, and the knowledge that older children who were vaccinated with Pfizer under the same strategy had excellent protection even during Omicron, suggests that for the most-feared outcomes, the vaccine appears to have worked.
3. This news has a very different flavor from the Pfizer data from late last year. Unlike the Pfizer study, Moderna’s study was successful in both the youngest cohort (starting at age 6 months) and the older one (starting at age 2 years) in its “primary endpoint,” (i.e. the antibody levels). In contrast, Pfizer had initially seen adequate responses in the younger of the two age groups it studied (ages 6 months to 2 years), but not the older one (ages 2-5).
4. Moderna’s press release indicates that the vaccine was safe and well-tolerated. The trial included 6,700 children, which is a large number in some ways and not in others. For common side effects, this trial is amply sized. Around 1 in 6 children had a low-grade fever. High fevers were exceedingly uncommon, at around 1 in 500. For example, for identifying side effects that would occur 1 in 1,000 recipients, a trial of this size would be likely to have uncovered a few instances. But what about myocarditis, the rare and mostly mild heart complication that has dogged trials especially involving adolescent and young-adult males? We don’t know. One thing we do know is that rates were not extremely high. If the rates of myocarditis had been 2-5 times greater than those seen in the highest risk males uncovered so far (ages 16-29, for the most part), then Moderna’s study might have been statistically expected to have one or more cases. However, there were zero cases. So while we won’t know what the rate will be until tens of thousands of young children are vaccinated, we can be confident that the risk appears yet again to be very low.
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Why was Moderna successful with its 2-dose regimen for children as young as 6-months old while Pfizer was not? I think it comes down to dosing. Pfizer chose a dose that is one-tenth of the adult dose, based on its earlier studies, while Moderna went with a dose that is one-quarter the adult strength. That likely explains the difference.
There will now be two big questions on people’s minds. Many will be asking, “When can I expect to get my young children vaccinated?” Likely this spring, but it will depend on the data presented to the FDA and CDC. Others will be asking, “Is vaccinating my young children even necessary?” To them, I would say yes. These vaccines continues to perform well in all age groups, and is safe—especially given the alternative.
Data from the CDC suggests that among children ages 0-4, there have been around 183 Covid-19-associated hospitalizations for every 100,000 children in the population (note: the rates among the infected are therefore obviously substantially higher). If we assume that these rates are true nationwide, that means that there have been around 35,000 Covid-19-associated hospitalizations among children ages 0-4 so far. While many of these may be “incidental,” it looks like a majority of these are actually caused either directly or indirectly by SARS-CoV-2.
Also, contrary to "contrarian" belief, a majority of children hospitalized for Covid-19 had no substantial medical co-morbidities. In any case, even if the highest rates of myocarditis occurred in this young age group, the quick math suggests that if every child under age 5 were to be vaccinated, up to 3,000 children (and likely far less, given the lower doses and new spacing of doses that lowers these complication rates) in the United States ages 0-4 would develop vaccine-related myocarditis (of which virtually all would be mild, given past experience). Meanwhile, if the vaccine reduces Covid-19-related hospitalizations by 75%, a reasonable guestimate, the vaccines already would have saved at least 25,000 hospitalizations in this age group if they had been available at the start of the pandemic.
Both Pfizer and Moderna are now studying 3rd doses in children of all ages. Whether they will be necessary will depend on what outcomes are tracked. But given what we’ve seen so far, the low-dose pediatric strategy has had one big upside in exchange for slower and less eye-popping efficacy results: lower doses have meant fewer side effects. That should re-assure many parents.
At the end of this, I suspect we’ll have a vaccine that is extremely safe and effective against the long-term consequences of SARS-CoV-2. With today’s sprinkling of data from Moderna, we are one step closer to herd safety.
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