The teenager arrived at the Oregon Health & Science University Hospital in late April with chest pains that had started suddenly. An MRI showed myocarditis: a swelling of the heart muscle. It’s something doctors at the Portland hospital see in young people a handful of times a year, says Judith Guzman-Cottrill, a pediatric infectious disease physician.
But the timing caught her attention: Just a few days before his symptoms started, the boy had received his second dose of Pfizer’s COVID-19 vaccine. A couple weeks later, Guzman-Cottrill received a call from a colleague in Atlanta who told her about a similar patient with myocarditis that started two days after his second Pfizer shot. The same day, she got news via email of two more such cases in Connecticut.
“Myocarditis in itself is not something so extremely rare that we thought this must be a new illness or new disease,” she says. “But when I heard about what was at that point four new cases—all healthy boys who developed chest pain, I thought, this seems almost too much to be coincidence.”
As of June 11, the U.S. Centers for Disease Control and Prevention has recorded 323 confirmed cases of myocarditis and pericarditis, a related condition, among people ages 12 to 29, mostly documented within a week after each patient had received one of the mRNA COVID-19 vaccines made by Pfizer-BioNTech and Moderna. That figure, announced this week by the CDC’s Advisory Committee on Immunization Practices, revises the previous count to include data from children ages 12 to 15, a group that gained authorization to get the Pfizer vaccine in May.
So far, post-vaccination myocarditis has been most commonly reported among people in their late teens and early 20s, according to the committee’s report. The condition is more likely to occur after the second dose, and it happens more often in boys and young men than in girls and women.
Overall, rates of post-vaccination myocarditis and pericarditis are higher than rates normally seen from other causes, Tom Shimabukuro, of the CDC’s COVID-19 Vaccine Task Force, said during the June 23 committee meeting announcing the results. But cases are still infrequent, and the vast majority of patients have responded quickly to treatment.
“This is still a rare event,” Shimabukuro said. “Reassuringly, the available outcome data indicate that patients recover from symptoms and do well.”
What is myocarditis?
When young people develop myocarditis or pericarditis (inflammation of the lining around the heart), the cause is often a viral infection. Enteroviruses such as hand-foot-and-mouth disease are among the most common triggers, and those infections are most common in the summertime, says Jeremy Asnes, chief of pediatric cardiology at the Yale School of Medicine in New Haven, Connecticut. There is also evidence of myocarditis after smallpox vaccination.
To get a handle on the apparent uptick of myocarditis in teenagers back in April, Guzman-Cottrill and colleagues took a detailed look at the experiences of seven healthy boys, ages 14 to 19, who sought care for chest pain in April or May. For all of them, symptoms began within four days after receiving the second dose of the Pfizer-BioNTech COVID-19 vaccine. Testing confirmed myocarditis or pericarditis. All seven recovered quickly, and three received common pain relievers such as ibuprofen as their only treatment, the team reported in a paper this month.
Those findings echoed several other case reports from the U.S. and Israel, which have suggested that post-vaccination myocarditis happens most often in younger people, especially men, says Matthew Oster, a pediatric cardiologist and epidemiologist at Children's Healthcare of Atlanta and a member of the CDC's COVID-19 Vaccine Task Force, who spoke at the ACIP meeting. Across those reports, cases have generally been mild, and recovery tends to be relatively rapid, with hospital discharge in two to four days instead of six, as is common with more traditional cases.
“It seems to disappear more quickly than typical myocarditis,” Oster said at the meeting. “I’m optimistic about that.”
The new data are consistent with that previous evidence. Of the 323 confirmed cases so far, 309 were hospitalized, Shimabukuro said. Among those, 295 have been discharged and 218 have recovered from all symptoms. Nine remain hospitalized and two are in the ICU. Most reports of myocarditis came within the first few days after vaccination, especially after the second dose. Cases peak in people in their late teens and early 20s and taper off after age 50.
The CDC’s numbers are also in line with what doctors report seeing in their own institutions. At his hospital in New Haven, Asnes says, his team has cared for 10 patients with post-vaccination myocarditis under age 21 and about the same number over 21. Stuart Berger, a pediatric cardiologist at the Northwestern University Feinberg School of Medicine in Chicago, says his group has seen six cases of confirmed myocarditis, mostly in boys ages 16 and up. All have been mild and included chest pain that went away quickly.
“This has been the experience that that the CDC has described,” says Berger, who is also a spokesperson for the American Academic of Pediatrics. “And it has been the experience that our colleagues and other institutions have described.”
Detecting rare side effects
Using data from the Vaccine Adverse Event Reporting System (VAERS), which allows anyone to report any potential issue related to vaccines, and the Vaccine Safety Datalink, which uses electronic health data from nine health care organizations around the country, the ACIP team calculated a rate of 12.6 cases of myocarditis or pericarditis per million within 21 days after the second dose of any mRNA vaccine in people ages 12 to 39.
The CDC continues to investigate reports submitted to VAERS, and Shimabukuro cautioned against focusing too much on the estimated case rate to guide decision-making in clinical settings. But in interviews, experts say the risk appears to be low compared to the number of vaccines administered.
As of June 22, more than three million 16- and 17-year-olds had received at least one dose of a vaccine in the U.S., and more than four million 12- to 15-year-olds had begun vaccination. “That denominator is very reassuring to me,” says Guzman-Cottrill, whose 16- and 13-year-olds have been vaccinated, including one with an autoimmune condition.
Rates of myocarditis have not been exploding, she adds, even as vaccine numbers grow. “Our emergency rooms are not filled with teenagers with chest pain.”
Link between vaccines and myocarditis
Scientists still don’t know how the vaccine might be causing myocarditis. One leading theory, Oster said, involves a cytokine response—the reaction of inflammatory molecules that rally immune cells to fight. That could explain why the condition appears so quickly after vaccination when it happens. Clinical trials have shown elevated rates of side effects such as fever, muscle aches, chills, and fatigue in young people compared with older adults, and those symptoms are caused by inflammation, Guzman-Cottrill says. So, it would make sense for myocarditis to be another inflammatory response at the most severe end.
The mechanism after vaccination is different from what happens in reaction to enteroviruses, Asnes adds. Instead of the direct invasion of a virus into the heart tissue, it’s the immune system itself that affects the heart after vaccination.
“There must be some cross-reactivity in some patients between their immune response to the vaccine and their heart muscles,” he says.
Facilities have taken different approaches to treating post-vaccination myocarditis, ranging from over-the-counter pain medication to intravenous medications and steroids. More clarity on mechanisms, as well as long-term follow-up studies, should help clarify the best treatment strategies. Further study may also explain why the condition is more common among males and how long recovery should be expected to take. Guzman-Cottrill plans to rescan her seven patients in August, three months after their initial diagnosis.
Given the latest numbers and the still-real risk of severe complications from COVID-19 among young people, including multisystem inflammatory syndrome, experts continue to recommend vaccination for teenagers.
“In the patients in this age group that we saw who were adversely affected by COVID, there were some very severe cases, so I still think that vaccination is appropriate,” Asnes says. “Like with any new therapy, we have to keep our eyes open. And that's what we're doing.