Skipping Second Dose of mRNA COVID-19 Vaccine May Limit Myocarditis in Adolescents

Moving to just one dose of an mRNA-based COVID-19 vaccine for adolescents appears to limit associated rare cases of myocarditis, according to a study out of Hong Kong.

Of 43 vaccine-related myocarditis cases identified, none occurred after a single-dose policy was implemented, lead author Xue Li, PhD (Li Ka Shing Faculty of Medicine, University of Hong Kong), and colleagues report in a JAMA Pediatrics research letter.

They estimate that about nine myocarditis cases were prevented with the change, but acknowledge that the analysis is limited by the small sample size in the post-implementation population. They also point out that study covered a period of time before the Omicron variant started circulating and when there was little local transmission of SARS-CoV-2 thanks to strict nonpharmaceutical control measures and an “extremely low” risk of COVID-19-related death or complications among adolescents.

“Vaccination policy for adolescents should consider the trade-off between risks and benefits,” Li et al say. “In countries with large outbreaks and to [prevent] local transmission, the risk-benefit assessment would favor a two-dose regimen because the single-dose regimen provides suboptimal protection from severe outcomes associated with COVID-19. However, in settings with no evident local transmission and stringent infection control policies, single-dose mRNA vaccination might be a viable option for offering protection to adolescents from severe outcomes associated with COVID-19.”

Shortly after countries started rolling out COVID-19 vaccines in early 2021, reports began to emerge about cases of myocarditis developing in the days following the shots, particularly the mRNA-based vaccines from Pfizer/BioNTech and Moderna. As more data were collected, it became clear that such cases—though rare—were concentrated in younger males and generally had relatively benign clinical consequences. Still, because of the higher rates seen in younger age groups, some countries—including Norway, the United Kingdom, and Taiwan—suspended the second dose of the primary series for adolescents. In Hong Kong, it was recommended that those ages 12 to 17 should receive only one dose of Pfizer/BioNTech vaccine, starting September 15, 2021.

Li et al examined the temporal relationship between this policy shift and cases of myocarditis reported after receipt of the Pfizer/BioNTech vaccine by linking vaccination records and electronic health records for adolescents ages 12 to 17 who received at least one dose between March 10, 2021 (when the Hong Kong vaccination program began) and October 18, 2021, excluding individuals with a prior history of myocarditis. The analysis included 224,560 first doses and 162,518 second doses.

Overall, 43 adolescents (mean age 14.86 years; 88% male) had a myocarditis-related hospitalization after receipt of the vaccine; 84% occurred after the second dose. The incidence rates per 100,000 people were 3.12 and 22.15 after the first and second doses, respectively, with corresponding numbers needed to harm of 32,051 and 4,515. All 43 myocarditis cases occurred among the 202,315 adolescents vaccinated before the single-dose policy change, with none among the 22,245 who received shots after that point.

Refining the Benefit-Risk Balance

Though Hong Kong went with the single-dose approach, there are other potential ways to mitigate the already low risk of myocarditis without compromising on efficacy against COVID-19 in adolescents, and Li et al highlight a couple: use of a lower dosage for the two shots in the primary series or an extended interval between the doses.

The US Centers for Disease Control and Prevention (CDC) has warmed to the second option, stating in guidance updated earlier this week that “an 8-week interval may be optimal for some people ages 12 years and older, especially for males ages 12 to 39 years.” The 3- to 4-week interval that has been used for the mRNA-based vaccines remains recommended for “people who are moderately or severely immunocompromised; adults ages 65 years and older; and others who need rapid protection due to increased concern about community transmission or risk of severe disease.”

We’ve seen enough COVID and we’ve had enough tragedy already that we have to continue to be vigilant and try to keep ourselves as vaccinated as possible. Elizabeth Schlaudecker

Commenting for TCTMD, Elizabeth Schlaudecker, MD (Cincinnati Children’s Hospital Medical Center, OH), was supportive of the change for the younger age groups, indicating that a changing pandemic situation allows for more-tailored recommendations to better balance risks and benefits.

“When we were first vaccinating a year ago or more, we were trying to prevent as many deaths as possible as quickly as possible. We were trying to get the pandemic under control and . . . we wanted to get as many people in the population vaccinated as quickly and safely as possible,” she said. “But now it’s sort of a different strategy. We’re trying to look ahead and think: how can we protect people for longer periods of time, so we don’t see a surge in COVID as time goes by?”

Accumulating data, as reported by the CDC, support both the safety and effectiveness of spreading out the two doses for longer intervals.

“The advantage of this spacing out by 8 weeks or more is that we are actually likely getting the same protection but we’re getting it for longer,” Schlaudecker said. “We are seeing a big decrease in infections, [so] we really have that luxury of being able to make sure that we’re [administering vaccines] really safely and preventing myocarditis by spacing it, and hopefully getting a more long-lasting immune response, which is great.”

As for whether a single-dose strategy—like that used in Hong Kong—could be useful in the US, Schlaudecker was skeptical. “We’re very optimistic that numbers are down, and everyone is feeling very encouraged by that, but I don’t think that this is the end of COVID forever,” she said. “I think we will continue to see possibly new variants that emerge, and some of them will be with us for a while, so if that’s the case then I think . . . the risk of just partially vaccinating our population is greater than the risk of deciding that it would be better to get two doses. I’m on the side that I still think that we’ve seen enough COVID and we’ve had enough tragedy already that we have to continue to be vigilant and try to keep ourselves as vaccinated as possible.”