Is Heart Inflammation a Hurdle to Vaccinating Kids?

The most reliable way to inflame the heart is to bother it with a virus. Many types of viruses can manage it—coxsackieviruses, flu viruses, herpesviruses, adenoviruses, even the new coronavirus, SARS-CoV-2. Some of these pathogens bust their way straight into cardiac tissue, damaging cells directly; others rile up the immune system so overzealously that the heart gets caught in the crossfire. Whatever the cause, the condition is typically mild, but can occasionally be severe enough to permanently compromise the heart, requiring lifesaving interventions including ventilators or organ transplants; in very rare cases, it’s fatal.

That is decidedly not what we’re seeing in the CDC’s recent reports. The agency has confirmed more than 500 cases of myocarditis or pericarditis—inflammation of the heart itself or of the lining that shrouds it—in people younger than 30 who recently received Pfizer-BioNTech’s or Moderna’s two-shot COVID-19 vaccines. These events are, so far, not matching the most terrifying versions of the condition, which have been observed with coronavirus infections. Rather, compared with more typical cases of myocarditis, the ones linked to the vaccines, on average, involve briefer symptoms and speedier recoveries, even with less invasive treatments. Still, the incidents are showing up in the few days that follow each vaccine’s second dose at higher-than-expected rates, especially in boys and young men, and no one is yet sure why.

The CDC’s Advisory Committee on Immunization Practices, or ACIP, met last week to weigh the risks and benefits of keeping the vaccines in circulation among the nation’s eligible youngest. It rapidly reached a familiar verdict: The perks of immunization far outweigh the potential drawbacks of these side effects and others. Days later, the FDA appended a warning about the rare events onto its fact sheets for the vaccines. Most of the experts I spoke with enthusiastically backed both agencies’ decisions without reservation. Vaccines, they said, remain our most powerful defensive tool against the coronavirus; if anything, staying unimmunized is the bigger gamble when it comes to severe organ inflammation. But several of them also noted that this particular side effect, and the country’s response to it, represents a new type of stumbling block for our inoculations.

The shots themselves, which are excellent, haven’t changed. But the context in which we’re deploying them has. This potential side effect is the first to concentrate like this in children, who are still relatively new to COVID-19 vaccination. Post-vaccine myocarditis still isn’t well defined; neither are the full consequences of pediatric COVID-19. For more than a year now, the pandemic has forced people to pit a pile of risky unknowns against another pile of risky unknowns, but anything that concerns kids’ health is bound to make tensions run particularly high. A recent Kaiser Family Foundation poll found that recent news of heart problems was a top-of-mind concern for many parents, who are often less likely to vaccinate their children than themselves.

The country’s situation is also very different from when the vaccines first arrived. Different types of shots are probably on their way, offering alternative routes to vaccination, perhaps without this particular risk. More versions of the virus are on our doorstep as well, and experts can’t confidently forecast our fates through the fall and winter. We are, once again, engaged in a game of pandemic chess, one that’s not getting much easier over time. We’re still figuring out the pieces we’re handling, and the crafty opponent on the other side; we’re relearning the rules, and the landscape of our board. And this next round, some of the most prominent players are our kids.

That the recent cases of post-vaccination myocarditis are relatively mild is, to start, “very reassuring,” said Judith Guzman-Cottrill, a pediatric-infectious-disease physician at Oregon Health & Science University (OHSU), who helped identify some of the earliest instances of inflammation back in April. Symptoms have lasted just a couple of days; most of the inflammation has been fairly straightforward to treat. According to Katherine Poehling, a pediatrician at Wake Forest Baptist Medical Center and an ACIP member, no deaths or severe outcomes had been reported at the time of last week’s meeting. “This is not like any myocarditis I’m used to seeing,” said Grace Lee, a pediatrician at Stanford and a member of ACIP. Though most of the identified patients have been hospitalized, “it’s because we wanted to monitor them, out of an abundance of caution,” said Sallie Permar, the chair of pediatrics at Weill Cornell Medicine and New York–Presbyterian Komansky Children’s Hospital. Many of these patients were discharged after receiving little more than over-the-counter pain medication as therapy. “Even the kids are asking, ‘Why am I going to the hospital?’” Permar said.

But vaccine-induced heart inflammation of any severity still warrants concern, especially without a known root cause. Myocarditis and pericarditis, which mysteriously skew young and male, can arise from an array of triggers, including bacteria and fungi as well as medications and autoimmune disease, but many cases go entirely unexplained. There’s no curative, or even standard, treatment for either condition; doctors try to manage symptoms and tamp down inflammation, said John Jarcho, a cardiovascular-medicine specialist at Brigham and Women’s Hospital, in Boston.

Cases related to vaccines are more puzzling still. Only a few immunizations have previously been linked to heart inflammation, among them the smallpox vaccine, which looks nothing like the jabs we’re doling out now. Researchers remain unsure what’s triggering the body to act out, or which children, especially which adolescent boys, might be most vulnerable. Mark Slifka, a vaccinologist at OHSU, told me he suspects the inflammation is caused by a bit of friendly fire—an extreme manifestation of the side effects already known to come with the Pfizer and Moderna vaccines, especially after the second injection. Perhaps immune cells are pumping out excessive alarm signals that marshal forces to the heart, or maybe the body’s defenders, confused by a vaccine ingredient, mistakenly wallop cardiac tissue. (Kids’ immune systems are generally feistier than adults’.)

We also don’t yet know whether these brief bouts of inflammation are leaving lasting damage, perhaps through subtle scarring of the heart, said Jeremy Asnes, a co-director of Yale New Haven Children’s Hospital Heart Center. His team has seen about a dozen adolescents with the conditions and will conduct follow-ups over the next several months. Guzman-Cottrill is doing the same in Oregon.

All of these factors make the risk of this complication tough to quantify, and several researchers have criticized the CDC’s recent evaluation. But most of the experts I spoke with said that the calculations still come out strongly in favor of vaccination, in part because of another set of disconcerting ambiguities, this time on the side of the virus.

SARS-CoV-2 does, on average, cause less severe disease in kids. But less is no longer a terribly comforting qualifier. Millions of young people have been infected; thousands  have been hospitalized; more than 300 younger than age 18 have died. We still don’t know how many kids hit by the virus will go on to develop long COVID, and the CDC has also logged more than 4,000 cases of a severe inflammatory complication called MIS-C. This condition can itself involve severe myocarditis—far worse than the cases that typically follow vaccination—and seems to carry a 1 percent fatality rate. It also disproportionately impacts people of color. “If you think about all the risks that come with getting COVID itself, those are way more common” than the very low myocarditis rates we’re seeing with vaccines, Permar told me. “If you’re playing the numbers, every time you would choose to vaccinate your child to prevent disease.”

Not all experts have taken the same stance; some have argued that there’s no rush to vaccinate kids. Coronavirus transmission in the United States has, after all, been dropping for months. But while absolute numbers of infections are down, the face of COVID-19 in this country has shifted. With vaccines concentrated among older adults, younger individuals are now shouldering more of the nation’s coronavirus burden: About a third of the infections reported to the CDC in May were in people ages 12 to 29, many of them unvaccinated. And the low spread we’re seeing right now won’t necessarily hold against the rise of highly contagious variants like Delta. It’s a terrible time to lose the momentum we’ve gained. “I’m not looking at transmission rates now,” Guzman-Cottrill told me. “I’m looking at what might happen in fall and winter.” Vaccination would shield kids, as well as those around them; immunizing more today means better protection later, even if we can’t yet see the threats on the horizon.

Read: The 3 simple rules that underscore the danger of Delta

Doctors are carefully monitoring new cases that come their way. If the inflammation they’re seeing continues to be mild, Asnes said, the people who experience it might be able to leave the hospital even earlier, or never check in at all. But if there’s an unexpected uptick in severity, experts will reassess.

More vaccine options could also change these calculations. For now, Pfizer is the only COVID-19 shot that can be used in children. But other vaccines with gentler side-effect profiles, including those from J&J and Novavax, could be easier on the heart, OHSU’s Slifka said.

In the interim, some experts have floated the notion of tinkering with Pfizer and Moderna dosing to safeguard younger heart tissue. Vinay Prasad, a hematologist-oncologist at UC San Francisco who has been very critical of the CDC’s evaluation of heart inflammation, told me he’d like to see the agency consider skipping second doses, or trimming doses down for at-risk populations. Neither of those strategies has been rigorously tested, though. Dose-reducing revisions run the risk of blunting protection, which might have contributed to the failure of the CureVac mRNA vaccine. Forgoing second doses could also backfire: Repeat shots seem crucial for conferring strong protection against variants like Delta.

Then again, kids aren’t just tiny adults, and adapting vaccines to their needs isn’t just a matter of bending down to stick a needle in a shorter, smaller person. Youthful immune systems react more enthusiastically to certain inoculations, which can mean more side effects, or simply that they need less vaccine to mount a defense. Several existing vaccines, such as the ones we use for chickenpox/shingles and tick-borne encephalitis, come in lower doses for children; Moderna and Pfizer are adopting this same strategy in their clinical trials for kids under 12. As they’re ushered into younger populations, our vaccines can be expected to undergo some growing pains.

The key, experts told me, is to stay flexible. Everyone’s chess board will end up looking a little different. Yale pediatrician Thomas Murray, whose two older children have already gotten their shots, told me he’s weighing the options with his younger son, who will soon turn 12. “We’ll engage in shared decision making,” he said. “I don’t want him to have to worry about him getting COVID.” Cornell’s Permar told me her family heard of the myocarditis reports the day before her 12-year-old son, Sam, was scheduled to receive his second dose of Pfizer. “We didn’t question it,” she said. “Looking at the numbers, there are so many more benefits of my son getting the vaccine.” Still, she kept a close eye on him for a few days after his shot.