Many parents have been anxiously awaiting the moment that Covid-19 vaccines become authorized for their children, hoping that the shots would provide confidence and security as the kids return to normal activities. Others have been more wary, concerned that rare side effects like myocarditis will outweigh the vaccine’s benefits considering that kids are less likely than adults to experience severe outcomes from the disease.
A variety of seemingly-conflicting headlines have added to the confusion about when the vaccines will be ready. Pfizer’s is the only vaccine authorized for children five and over, but Moderna’s was expected to be authorized for adolescents (age 12 to 17) in the fall of 2021 until the FDA said it needed more time to review potential adverse reactions. In the meantime, Moderna completed its trial on younger kids, ages 6 to 11, but rather than submitting that data to the FDA, the company said it would wait until the agency finished reviewing the previously-submitted adolescent data. Pfizer planned to end the clinical trials for patients under five near the end of 2021, but in February 2022, changed course and added a third shot in hopes of increasing efficacy in the midst of Omicron.
The whirlwind of news has left many parents scratching their heads and full of frustration. Smithsonian reached out to experts to understand what the future might hold.
Why are separate trials needed for children?
In order to be authorized for use in kids, any drug or vaccine needs to undergo child-specific clinical trials, which usually occur after a drug has already been proven safe in adults. Kids are not just small adults and adjusting the doses based on their size isn’t enough to guarantee safety and efficacy. “Children’s immune systems are still building, so sometimes children will respond slowly or not at all to vaccines,” says Mobeen Rashore, an infectious disease pediatrician at the University of Florida. Sometimes they need additional doses to coax their immune systems to develop a sufficient response.
Other times, they may respond more robustly than adults, leading to additional side effects. “If you give kids a higher dose of vaccine, it’s possible that they have more side effects. More fevers, they can have more swelling of the arm, or they can have more pain, or other things that we don’t know about,” says Rashore. Still, “you don’t want to give a vaccine dose that is so small that it’s not effective.”
“For some pathogens kids simply don’t need as much [as adults],” says Buddy Creech, a pediatrician at Vanderbilt University and a principal investigator in Moderna’s pediatric vaccine trials. “With influenza, we historically have given a slightly smaller amount. For other vaccines, it really doesn’t matter as much.”
Moderna and Pfizer have been testing smaller doses of their Covid vaccine on children to see if they can provide protection without raising side effects.
What vaccines are available for kids and how well do they work?
So far, Pfizer’s vaccine is that only one authorized for patients 5 to 17 years old. No Covid vaccines have been authorized for those under 5.
Scientists and regulators use two main strategies to evaluate effectiveness of Covid vaccines in younger populations. The first, of course, is comparing the number of Covid cases in a vaccinated group of patients to that in a group of patients who received a placebo. However, it can take a long time for there to be enough cases to reach statistical significance, so they also look at the immunogenicity—a measure of how strongly the immune system responded to the vaccine. By measuring the number of antibodies a child produces after vaccination and comparing that to the number of antibodies adults produced, the researchers can reasonably assume a similar level of protection.
In May of 2021, the FDA authorized Pfizer’s vaccine for adolescents aged 12 to 15. Out of about 1,000 patients who received the vaccine, no cases of Covid-19 occurred a week after vaccination. In the placebo group, 16 cases occurred. Those who received the vaccine also showed similar levels of antibodies to those of vaccinated young adults (16 to 25 years of age).
The Pfizer vaccine was authorized for children 5 to 11 years old on October 29, 2021. The clinical trials showed that a dose of 10 μg elicited similar immune responses to the 30 μg dose for those 12 to 15 years old and was about 90 percent effective at preventing Covid-19.
Moderna published results of its trials of two 100 μg shots in 12 to 17 year old patients in the New England Journal of Medicine in August of 2021 and applied for FDA authorization, but in October, the company announced that the FDA needed more time to review the possibility of an increased risk of myocarditis in this age group. In the same month, the company published a press release with data from its trial of two 50 µg shots in 6 to 11 year olds that said the children mounted an immune response comparable to that of adults, but the full results are not yet available and the company won’t submit it to the FDA until the review of the adolescent data is complete.
As the Omicron variant took hold, researchers have found that the vaccines were less effective against infection in individuals of all ages, however they still provided substantial protection against hospitalization and death. The Centers for Disease Control and Prevention (CDC) published a report on March 11, in which over 1,200 children aged 5 to 15, both vaccinated and unvaccinated, were tested for Covid-19 weekly between July 2021 and February 2022, regardless of whether or not they showed symptoms. As Omicron surged, the Pfizer vaccine reduced the risk of infections (symptomatic and asymptomatic) among 12 to 15 year olds by 59 percent and 5 to 12 year olds by 31 percent.
Why hasn’t a vaccine been approved for kids under 5 years old?
During the rise of Omicron, the companies were also running trials for the youngest patients: kids under the age of five. While Pfizer had originally announced that it expected the shot to be available by the end of 2021, it instead published a press release in February saying that it would be adding a third shot to the regimen to see if it could coax a more robust antibody response. The company expects new results in early April.
Adding a third shot is the most practical option for Pfizer. First, the company won’t have to start an entirely new trial with new participants at a different dose. Second, the company can reduce the risk of increasing side effects by not increasing the dose. Pfizer is using a 3 μg dose in each shot because in early-phase trials, a larger 10 μg dose caused high fevers in many of the children, an outcome that was minimized with the smaller dose.
Moderna, on the other hand is testing two larger doses, 25 μg, four weeks apart. Data is expected this month.
Are there any vaccine safety issues or side effects unique to children?
Kids tend to fare better than adults if they get sick with Covid-19, but there is one long-term outcome unique to these younger patients: multisystem inflammatory syndrome in children (MIS-C), a dangerous condition that can cause a variety of symptoms from dizziness and vomiting to bloodshot eyes and often leads to hospitalization after a child recovers from Covid.
“We've been monitoring for that very closely,” says Creech. “And thankfully, we have not seen that side effect occur outside of some extraordinary situations which seem to be linked more to a recent infection than to the vaccine.”
The other concern is myocarditis, an inflammation of the heart muscle characterized by shortness of breath, chest pain and the feeling that the heart is beating rapidly. So far about 70 out of every million boys age 12 to 15 and 105 out of every million boys age 16 to 17 experienced myocarditis a week after vaccination. “It is fairly rare that we have seen it,” says Marcos Mestre, a chief medical officer at Niklaus Children’s Hospital in Florida. “And we haven’t really seen many cases at all in the 5 to 11 year age range.”
In a study published in December of adolescents and young adults who experienced myocarditis after Covid vaccination, all patients recovered fully, and most were treated only with non-steroidal anti-inflammatory drugs (NSAIDS).
Why hasn’t uptake been high for those kids eligible to get the vaccine?
Since Pfizer’s vaccine was authorized for teens and kids five and over, the number of kids getting vaccinated has fallen far below healthcare experts’ hopes and expectations. By March 16, only 60 percent of 12 to 17 year olds and 27 percent of 5 to 11 year olds had been fully vaccinated.
There are several reasons why parents may be hesitant to vaccinate their kids, which Rathore calls “a shame.”
The first is that the disease is less likely to be severe in children than it is in adults. “If you look at rates of immunization, they seem to track with how severe the illness often is in that population. We've done a fantastic job of vaccinating the over 65 population, because the mortality was rightly seen as quite high and as individuals, the younger you get, maybe there's less of a recognition that there can be significant consequences to the disease,” says Creech.
“It's true that children don't often get as sick as adults do. But they do get sick,” says Rathore.
And “they can get the dreaded MIS-C still.”
Another factor is that by the time the vaccines for younger patients were approved, many children may have been infected and recovered. “With some rationale, which I don't disagree with, they said, ‘Well, I'm protected for a certain period of time,’” says Mestre, so they might delay vaccination.
Lastly, mixed messaging has left some parents concerned and confused. On March 8, the Florida surgeon general announced that the state would not be recommending the vaccines for healthy children. In response to the announcement, Rathore, who practices in Florida, says “Most pediatricians and other physicians, the American Academy of Pediatrics, CDC, WHO and almost all other credible organizations recommend that children five years and older be vaccinated with Covid vaccine to protect them. I am in agreement with this position that all eligible children should be vaccinated with Covid vaccine to protect our children.”
What should parents with children under 5 do now?
Rathore wants to assure parents that the delay has nothing to do with safety. “There’s no question about safety,” he says. “No parents should have that concern. The only thing we’re trying to make sure is that children are given an effective dose on an effective schedule.”
In the meantime, Mestre says that, “I understand as a parent myself the anxiety that’s caused by having the Covid infection,” says Mestre. “I would tell them to make sure everybody else in the household that’s eligible to be vaccinated receive the vaccine. . . to decrease the risk to that younger child,” while continuing to use other mitigation measures like masking and distancing.