One afternoon in May, Michael Joseph Smith, a paediatric infectious disease specialist, strides in baseball-patterned socks through a Duke University facility in Durham, North Carolina, to welcome Cameron O’Hara, a 14-year-old vaccine trial subject. Smith has been acting as co-principal investigator at one of the sites that’s been testing the Pfizer-BioNTech vaccine in children.
O’Hara and his mother have come to the office after the “unblinding” process — in which he’d learnt, to his disappointment, that he’s been getting a placebo — to get his first dose of the real thing. He crosses his sneakers and grips his mother’s hand as the needle goes into his arm.
O’Hara is eager to return to the classroom as a high school freshman. He’s planning to celebrate his second dose with a road trip to the Adirondacks to see his grandparents. “The first thing I’m going to do is give them a hug,” he says, bringing his mother to tears. O’Hara’s parents, both pharmacists, encouraged his enrolment in the trial. He’s more enthusiastic about vaccination than many of his friends, some of whom fear needles, some of whom carry youthful delusions of immortality.
Smith worries that laissez-faire attitudes about vaccinating adolescents could slow the US paediatric immunisation campaign and even cost lives. Though Covid-19 has taken its greatest toll on older adults, over the past year he’s seen infected children develop fatigue, brain fog and chest pain — all symptoms of “long Covid”. And his hospital has treated dozens of cases of multisystem inflammatory syndrome, or MIS-C, a sometimes deadly paediatric condition associated with Covid. His concern has increased as the more-transmissible Delta variant has become the nation’s dominant strain. “A lot of people think this is going way too fast,” he says of the clinical trial process. “It’s not. We’ve just removed the bureaucratic red tape.”
Though paediatric studies moved quickly, the rollout of shots to millions of youngsters age 12 to 17, who account for 7.5% of the US population, has lagged. Only 43% have received their first dose. That’s led the White House to call upon schools, community organisers and even the Gen Z pop star Olivia Rodrigo to double down on pitching the vaccine’s benefits before the school year starts.
More than 4-million children in the US have tested positive for Covid, but the true number of infections is likely much higher, because children are often asymptomatic and they’re less likely to be tested. In recent months, as a growing number of adults have been vaccinated, children have at times accounted for more than a third of confirmed weekly cases. At least 44,000 children, from newborns to 17-year-olds, have been hospitalised since August, and about 350 have died, according to the US Centers for Disease Control and Prevention (CDC).
Peter Marks, the director of the Center for Biologics Evaluation and Research at the US Food and Drug Administration (FDA), says 350 deaths from Covid might not sound like many, but “when you think about childhood illnesses that are vaccine-preventable, that is a lot”. And as with adults, Covid has taken a disproportionate toll on those from racial and ethnic minorities and those with underlying health conditions such as asthma, diabetes and obesity.
Guliz Erdem, a paediatric infectious diseases physician at Nationwide Children’s Hospital in Columbus, Ohio, is frustrated by what’s seemed, at times, to be widespread dismissal of the risk Covid poses to children. She’s tended to MIS-C patients as young as two months old, who appear in the emergency room with swollen hands, bloodshot eyes and blue lips. She describes the syndrome as a bomb that explodes in the body and fragments the immune system. “At first we didn’t really believe this condition was real,” she says. It was months before the CDC started counting cases, but from May 2020 to July 2021, the agency received more than 4,100 reports of MIS-C, including 37 deaths, with most cases occurring in black and Hispanic children and those younger than 14.
The other major impetus behind vaccinating children, beyond their own health, is the contribution it could make to ending the pandemic. Children make up more than 25% of the global population, which many scientists say makes them key to reaching the goal of herd immunity, estimated at protection for at least 70% of the population. (That number could be higher as variants continue to emerge.)
The longer that other countries delay vaccinating children, the longer it will take to significantly slow the spread of this virus
— Paul Offit
The US government campaign to immunise children before the school year began in May, when an emergency-use authorisation (EUA) was granted for the shot produced by Pfizer and its development partner, BioNTech. The companies ran their paediatric trial soon after the adult one, finding that their vaccine was 100% effective at preventing symptomatic Covid in 2,260 children age 12 to 15 and that the subjects produced antibodies exceeding levels seen in vaccinated young adults, without exhibiting new or worrisome side effects.
Moderna applied for US clearance, after also seeing 100% efficacy in its trials for 12- to 17-year-olds, and has already received a green light from European regulators. Novavax and Johnson & Johnson are currently testing their vaccines in adolescents. Early UK trials for the shot from AstraZeneca have been delayed in the wake of rare blood clots found in adults who’d had the vaccine.
Pfizer has shifted to study even younger children, enlisting as many as 4,500 six-month- to 11-year-olds to get lower-dose shots in the US and Europe, with initial data expected as early as September.
Ensuring that vaccines are ready for all children by year-end is “our best hedge against preventing a nasty variant of the future”, says William Gruber, Pfizer’s senior vice-president for vaccine clinical research & development. “There will be a risk-benefit assessment as we see where the pandemic is at that particular time.”
The risk-benefit discussion promises to become even more pointed when Covid immunisation expands to younger children — and if schools begin to implement mandatory vaccination, as they already do for any number of diseases. Already, the rates for children are falling along red and blue lines, much as they have for adults. To help end the pandemic in the US, the Biden administration will have to keep trying to build confidence among hesitant parents, continue vaccinating older children and speedily deploy shots for younger ones. If the rollout succeeds, it could redefine the global approach to the fight against Covid.
With vaccine scepticism and misinformation spreading, the CDC has continued to stress the scientifically settled principle that school mandates are a critical public-health tool. With Covid, though, the Biden administration has left that to others to debate. No states have yet ventured to put such a policy in place.
Biden’s overseas counterparts initially moved more slowly on vaccinating children. The UK, for example, has been limiting its rollout of the Pfizer shot for children to only the most vulnerable 12- to 17-year-olds and those living with at-risk adults. But more than half of EU nations have started to vaccinate healthy children, and debates about mandates have begun. China has taken an aggressive approach, with its regulator granting emergency authorisation for Sinovac Biotech and Sinopharm Group shots to be used in children as young as three, even though trials are ongoing. Some Chinese provinces are vaccinating older children this northern hemisphere summer.
For most countries, the decision about whether to offer vaccines to children is being driven by supply, especially in places where shots are still badly needed for adults. But the risk of new waves of infection driven by young people also matters. “The longer that other countries delay vaccinating children,” says Paul Offit, an infectious disease specialist at the Children’s Hospital of Philadelphia and an adviser to the FDA, “the longer it will take to significantly slow the spread of this virus.” He notes that waiting gives the virus time to mutate into variants that can potentially evade existing vaccines.
The US campaign for children aged 12 and up will provide new information about the vaccines’ safety profile. That nearly 9-million 12- to 17-year-olds have completed their regimen has, for many, demonstrated the Pfizer shot’s safety. But some possible issues have surfaced that weren’t evident in the much smaller trial. In June, US health advisers met to discuss a link between mRNA vaccines and myocarditis and pericarditis — inflammation of the heart muscle and its surrounding membrane, respectively.
The CDC had noticed a spike in cases, particularly among male teenagers, with more than 1,200 counted at the time of the meeting. Its data showed there was only a 0.00126% chance that those 12 to 39 years old would develop either heart condition within 21 days of being administered their second dose, and most who develop the condition quickly recover after treatment and rest. The agency’s advisers noted that Covid-caused conditions such as MIS-C pose a greater threat. And with the Delta variant “more readily impacting younger people”, as the CDC, the American Academy of Pediatrics and other organisations said in a joint statement, that small risk shouldn’t deter families from heading to the clinic. In the UK, by contrast, the heart risks informed its decision not to give the shot to healthy children yet.
The discussion will be even trickier when it comes to younger children. Pfizer is expected to report its trial data on those age five to 11 as soon as September, and on those age two to four shortly thereafter, potentially clearing the way for an EUA before the end of the year. Gruber, the Pfizer executive, estimates that data for the six- to 24-month-old group will be ready as soon as October. The new trial results — which will be based on a dose one-third the size of that for adults for children age five to 11 and one-tenth for children under five — will look different from previous ones. Because there are now fewer Covid cases in the US than in 2020’s northern hemisphere winter, Pfizer likely won’t report efficacy data that compares cases among vaccinated participants against those in a placebo group. Instead it will assess the immune response the shot prompts.
Is it fair to vaccinate somebody and expose them to the very small risk of the vaccine if the benefit is predominantly for the population?
— Nigel Curtis
This method is often used to validate paediatric vaccines, but the absence of clear efficacy numbers along the lines the public has grown accustomed to for Covid vaccine trials will be one more new variable for parents to consider. Despite the long-term risks to younger children who get the disease, it hasn’t been seen in them in numbers suggesting as urgent a need to vaccinate them for their own health, for reasons that still aren’t properly understood. (Hypotheses include that the cells controlling blood-clotting are healthier and therefore less susceptible to infection, that they have fewer of the receptor cells that allow the virus to gain entry and that their immune systems are innately stronger.) It’s also not known at what age children might become more vulnerable.
“I don’t think that we know the accurate balance of benefit and harm from these vaccines in young children,” says H Cody Meissner, a paediatric infectious disease expert at Tufts University School of Medicine and an FDA adviser. It’s important to compare the potential for adverse effects against the potential for Covid hospitalisations, he adds. “If it’s higher, then we’re causing more harm than we’re preventing.”
The more the argument for vaccinating younger children rests on getting to herd immunity, the more officials and scientists will have to consider the ethics involved. The question becomes: “Is it fair to vaccinate somebody and expose them to the very small risk of the vaccine if the benefit is predominantly for the population?” says Nigel Curtis, a paediatric infectious diseases physician and researcher at the University of Melbourne and Murdoch Children’s Research Institute. “I’m just amazed by how people are so certain about what the right thing to do is.”
To quell concerns about safety, Meissner suggests the FDA first grant a full biologics licence for the shot in younger children, rather than an EUA, before expanding the rollout. Pfizer is likely to get full approval for those 16 and up as soon as this northern hemisphere autumn, but it will take longer to get it for those who are younger, as the FDA requires six months of safety data. Waiting could fundamentally change the rollout, however, helping sway parents worried about legitimate side effects and dispelling concerns, unfounded though they may be, about unapproved technology. It could also give officials cover to mandate vaccines in schools without quite so much fear of retribution.
Marks, the FDA director responsible for vaccines, says, “As we get down below age 12, we’re going to be looking even more critically at the safety data, so that we make sure that we’re very convinced that the children are getting as much direct benefit as they possibly can.” To that end, US regulators have asked Pfizer and Moderna to at least triple the size of the under-12 trials.
“The other worry,” Marks says, “is that it’s been a little while since we had a new Greek letter.”
Rod Jenkins, the local public-health director, and his team in Durham have done meticulous geomapping, cross-referencing neighbourhoods with the highest rates of social vulnerability and lowest vaccination rates to determine where to place pop-up clinics for teens. Then they make sure community organisers are running the show. Hillside, a historically black high school, was chosen as a site through this model, along with a fun park that has a go-kart track and a roller rink. The aim is to bring in not only children but their parents, too. “How awkward would it be to see your kids vaccinated, with their TikToks and their school’s town halls, and you yourself not be, as a caretaker?” Jenkins asks.
If the vaccination campaign is a marathon, we’re at Mile 20, he says solemnly. It’s the toughest part of the race, especially with Covid cases and hospitalisations rising once more. Jenkins has a final sprint planned for the four days before children return to the classroom: a back-to-school immunisation event at Durham County Memorial Stadium. “I’m really weary,” he says. “We don’t want to have a situation where kids have to vacate the classrooms.”
For John Osorio Vasquez, the patchwork rollout means he won’t likely be able to forgo his mask in the classroom, as he’d hoped to at his summer job. Durham Public Schools (DPS) require face coverings for students and staff, regardless of whether they’ve been vaccinated — an approach the CDC backed in late July. “Many of our families, teachers and staff feel more secure with universal masking,” says DPS spokesperson Chip Sudderth. No vaccine mandate is in the offing, at least for now, which means carrying on with the painstaking process of persuading everyone to get their shots.
But where adults are weary and wary, children remain hopeful. John’s brother, Diego, already feels freer. His father has long promised to take him to El Salvador. John has been a handful of times, and it’s finally Diego’s turn. The country has recently faced a surge in cases, but with a shield of protection, Diego thinks his odds have improved. He grins. “It’s a good time to get my vaccine.”
Bloomberg Businessweek. Bloomberg News. More stories like this are available on bloomberg.com.
Would you like to comment on this article?
Sign up (it's quick and free) or sign in now.
Please read our Comment Policy before commenting.