Last week in the United States, more than 1 million COVID-19 cases were reported in a single day, schools resorted to virtual instruction, and COVID outbreaks among staff left hospitals struggling to attend to their ever-growing number of COVID patients. Also, the CDC endorsed Pfizer booster shots for teenagers, saying not only that every American 12 and up can get one, but that they should.
The latest recommendation on boosters feels like a natural response to the Omicron variant’s lightning-fast spread: With so many Americans getting exposed to the coronavirus, vaccination is more important than ever. Yet the risk-benefit calculus around third shots—particularly for teenage boys and young men—may be even more complicated than it was before the present surge in cases. The new variant’s knack for sneaking past immune protection, combined with its mildness relative to Delta, makes its actual value, in terms of harm averted, that much harder to assess. And whatever protection it does afford must still be weighed against the incremental (but very small) risk of heart inflammation that comes with each mRNA-vaccine injection. Simply put, Omicron has added substantial new uncertainty to what was already a difficult equation.
Inflammation of the heart muscle, called myocarditis, typically arises in children and young adults after they recover from a viral infection such as Coxsackievirus or adenovirus. It can cause chest pain, heart palpitations, and arrhythmias, and in the worst cases, fatal shock or heart failure. Patients with mild myocarditis might not get sick enough to need medical attention, but in some extremely unusual cases they may develop arrhythmias that lead to sudden death. Patrick Flynn, a pediatric cardiologist at Weill Cornell Medicine, told me that specialists haven’t figured out any risk factors for myocarditis besides sex—boys are more susceptible than girls—nor can they predict who will get very sick from the condition, or who might die from it without warning. “It’s really largely random,” he said.
Myocarditis associated with COVID-19 vaccines is rare, and tends to affect a very specific group: boys and men in their teens and early 20s who have received mRNA-based shots. It is overwhelmingly mild. As of last month, 265 reports that met the definition of myocarditis in kids ages 12 to 15 were filed to the Vaccine Adverse Event Reporting System, and 92 percent of the patients had recovered. Only a handful of fatal cases have been reported worldwide. Second shots have produced far more reports of myocarditis than first shots, at about 70 cases for every million 12-to-17-year-olds who finish their vaccine series. And early data from Israel, where teens have been eligible for boosters since last August, indicate that myocarditis rates might be lower after third doses than second doses.
All of these numbers are likely undercounts, Walid Gellad, a professor at the University of Pittsburgh School of Medicine, told me; one study from Oregon that has not yet been peer-reviewed looked for myocarditis cases that might have been missed by the standard surveillance system, and estimated the incidence among 12-to-39-year-old boys and men to be 195 cases per million second doses administered (and higher for men ages 18 to 24). But the study was working with small margins—just a handful of cases, in the population it examined, that might have been missed—and the exact degree of underestimation is difficult to pin down, Flynn said.
Even allowing for this bias in the stats, for the overwhelming majority of people—including boys and young men—the risks of developing myocarditis after a booster shot are minimal. Flynn said that the only patients he would consider advising not to take the shot would be those who had developed myocarditis after their second dose. But not all the experts I spoke with agreed. Paul Offit, the director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told me that getting boosted would not be worth the risk for the average healthy 17-year-old boy. Offit advised his own son, who is in his 20s, not to get a third dose. Even with Omicron’s ability to sidestep some of the protection vaccines provide, Offit said, he believes that his son is well protected against serious illness with two shots, so a third just isn’t necessary.
Young people are generally at much lower risk of severe COVID than older people, which is one of the reasons that boosting them was controversial to begin with. And if Omicron causes less severe disease than Delta, the benefit of boosters might be smaller still. But the United States is positively drowning in coronavirus right now. “It’s not a theoretical risk,” Gigi Gronvall, an immunologist at the Johns Hopkins Center for Health Security, told me. “You are going to get exposed to the actual virus.” Each individual teen’s risk of bad outcomes if they do get infected might be small, but each individual teen is also now much, much more likely to get infected in the first place, thanks in large part to Omicron. (Gronvall’s 14-year-old son has a booster appointment for this week.)
All those infections don’t have to be severe to be harmful. Missing school and work has real consequences for families. And MIS-C, a dangerous post-infection syndrome that can affect the heart (among other organs), has shown up in kids who had even mild bouts of COVID. Compared with MIS-C, Flynn said, the sort of myocarditis that vaccines have tended to cause is a walk in the park. “I think every pediatric cardiologist I’ve talked to would rather be seeing cases of vaccine myocarditis than ever seeing a case of MIS-C again,” he said. The latest CDC data indicate that two doses of the Pfizer vaccine were 91 percent effective at preventing MIS-C in 12-to-18-year-olds when Delta was king; it’s too early to tell what that number is in the Omicron era, or by how much a third dose might increase that protection. Gellad said that if MIS-C turns out to be much more common with Omicron, he might be convinced that every teen boy needs a booster. But for now, he thinks the benefits vary patient by patient. A teen who lives with an organ-transplant recipient, for example, might have more to gain from a booster than one whose household is otherwise made up of vaccinated-and-boosted adults with healthy immune systems.
In the long term, boosting could end up being more effective for teenagers, shot for shot, than it is for adults. Younger people have more robust immune systems, says Sallie Permar, the chair of pediatrics and a viral-infections specialist at Weill Cornell, so they may develop stronger post-vaccine protection as a result. In other viral diseases such as hepatitis C, HPV, and HIV, she told me, a vaccination or bout of infection in early childhood has been shown to confer longer-lasting immunity against more variants of the pathogen than an encounter later in life. The same could be true of SARS-CoV-2 and the COVID-19 vaccines, Permar said: You might be better off getting three doses before you’re all grown up.
For millions of young people in the U.S., this entire discussion is irrelevant: As of last Friday, 46 percent of 12-to-17-year olds, and 41 percent of 18-to-24-year-olds, are yet to be fully vaccinated. The benefits of getting those first two doses are beyond question. For the teen boys and young men who are staring down the possibility of a booster, setting up a dichotomy—avoiding Omicron versus avoiding myocarditis—amounts to a “false choice,” Gellad said. Men 18 and older can mitigate their myocarditis risk by choosing Pfizer’s shot over Moderna’s, given that the latter has been linked to higher myocarditis rates. And boys under 18, who are eligible for only the Pfizer jab, may eventually have an option to get a smaller booster dose, which should carry a smaller risk of side effects.
Omicron adds one more important wrinkle to decision making about boosters: It’s a reminder that our current best practices could change at any moment. Until the overwhelming majority of the world is vaccinated, new variants are likely to emerge from one season to the next. “If this is the last wave, then that’s great. And a lot of the questions that we’re asking and a lot of the answers that we’re struggling with become moot,” Flynn said. But if it’s not, then a third dose could provide essential protection against the next variant—and Americans who avoid a booster now could find themselves regretting their complacency.