The complication was generally rare, but is more commonly seen with the Moderna versus Pfizer / BioNTech COVID-19 vaccine.
In one of the largest studies to date investigating the incidence of myocarditis following mRNA-based COVID-19 vaccination, the risk of complication – although generally low – was higher among people receiving the Moderna syringe than it was with it from Pfizer / BioNTech, researchers report.
Men aged 16 to 24 were most likely to develop vaccine-associated myocarditis within 28 days of vaccination, and in this group, the estimated number of excess events per 100,000 vaccine recipients between four and seven after a second dose of the Pfizer / BioNTech shot and between 9 and 28 after a second dose of the Moderna shot.
The difference between mRNA vaccines, according to previous research, has now been confirmed in one of the best available data sources – total national registry data of more than 23.1 million people living in Denmark, Finland, Norway and Sweden, according to senior author Rickard Ljung, MD, PhD (Swedish Medicines Agency, Uppsala, Sweden).
“The risk is clearly higher for Moderna,” Ljung told TCTMD, adding that the higher amount of mRNA in that shot versus that from Pfizer / BioNTech may explain the difference. He noted that “not only in Sweden but also in Finland and in Norway, the public health authorities have changed the recommendations [to advise] does not use Moderna, at least for younger men. “
Some other countries have followed suit. Advisers to the US Centers for Disease Control and Prevention (CDC) discussed the issue at a meeting in February, as reported by CNBCalthough the CDC has not issued a recommendation to limit the use of the Moderna vaccine to certain age groups.
The higher incidence of myocarditis with the Moderna shot should be considered in the context of other research suggesting that the vaccine may provide greater protection against SARS-CoV-2 than the Pfizer / BioNTech vaccine, the study authors state: “This risk should be balanced against the benefits of protecting against serious COVID-19 disease. “
Myocarditis and Pericarditis Rare in general
After countries began rolling out the mRNA vaccines, which have been shown to safely reduce the risk of severe COVID-19 outbreaks, reports of myocarditis associated with vaccination began to emerge. Subsequent research has established a clear link between the Moderna and Pfizer / BioNTech vaccines and an increased risk of myocarditis, where cases are grouped according to the second dose and among younger men. The clinical course in affected patients has generally been mild. Other analyzes have established that there is a risk of myocarditis / pericarditis caused by COVID-19 the infection itself exceeds the risk after vaccination, even in younger men.
The current survey – published online Wednesday before print in JAMA cardiology, with lead author Øystein Karlstad, MScPharm, PhD (Norwegian Institute of Public Health, Oslo, Norway) – dives into the question by collecting data on residents aged 12 and older from four Nordic countries. The study period ran from 27 December 2020, when national vaccination campaigns were launched, to 5 October 2021, the day before the Swedish health authorities recommended the use of the Moderna vaccine for men and women under 30 years of age. Cases of myocarditis and pericarditis were identified using diagnostic codes.
During the study period, 81% of subjects received at least one vaccine dose – 65% with the Pfizer / BioNTech vaccine, 10% with the Moderna vaccine and 6% with the Oxford / AstraZeneca syringe.
In the 28 days after vaccination or during unvaccinated periods, 1,077 cases of myocarditis and 1,149 cases of pericarditis were identified. Both the first and second doses of the mRNA vaccines were associated with a higher risk of these complications compared to unvaccinated periods, especially in the first 7 days after the second dose and among men.
Among those on a homologous schedule (same vaccine for both doses), the second dose was associated with a higher risk of myocarditis compared to unvaccinated periods, both for the Pfizer / BioNTech shot (adjusted incidence ratio). [IRR] 1.75; 95% CI 1.43-2.14) and the Moderna vaccine (adjusted IRR 6.57; 95% CI 4.64-9.28). Both figures were higher for men versus women.
Men aged 16 to 24 were most at risk with adjusted IRRs of 5.31 and 13.83 after the second dose of the Pfizer / BioNTech and Moderna vaccines, respectively. The number of excess events per 100,000 vaccinated in this group were 5.55 and 18.39 with the two vaccines. Excess events peaked at 27.49 per 100,000 vaccine recipients among young men who received a mixed series involving a Pfizer / BioNTech first dose followed by a Moderna second dose.
In general, there were similar estimates for pericarditis, the authors report.
Deaths in patients with myocarditis were rare, they say, citing a 28-day mortality rate of 0.8% among unvaccinated cases, 0.2% after another Pfizer / BioNTech dose and 4.5% after another Moderna dose. . There were no deaths associated with myocarditis in persons under 40 years of age.
“Although studies of the long-term prognosis of vaccine-associated cases of myocarditis are lacking and urgent need, some evidence suggests that 28-day risk of death, hospitalization rates and development of heart failure appear low, especially in younger age groups,” the researchers write.
Ljung added: “It is not clear that this myocarditis after vaccination should be more severe than a normal myocarditis. I think that is important. And it is also important to know that most of the myocarditis you can get is generally quite mild. Although it is a serious event, it is not usually a life-threatening event. “
Balancing risks and benefits
In an accompanying note, Ann Marie Navar, MD, PhD (UT Southwestern Medical Center, Dallas, TX), Vice Editor for Diversity, Equality and Inclusion of JAMA cardiologyand Robert Bonow, MD (Northwestern University Feinberg School of Medicine, Chicago, IL), editor of the journal, look at the clinical implications of the results.
First, “older adults who have the highest risk of COVID-19 complications appear to have an extremely low risk of vaccine-associated myocarditis,” they point out, adding that “the benefits of immunization in those older than 40 year clearly outweighs the risks. “
Navar and Bonow suggest that considerations may be different in younger people, especially men, where the risk of myocarditis is much higher. Young men, they say, may choose the shot from Pfizer / BioNTech over the one from Moderna to reduce the risk of myocarditis, and health professionals may consider recommending that approach to certain groups, “including young men and other individuals for whom myocarditis concerns constitutes a barrier to immunization. “
However, like the authors of the study, Navar and Bonow advise to weigh the lower risk of myocarditis with the Pfizer / BioNTech vaccine against the possibly improved protection against severe COVID-19 outcomes with the Moderna vaccine.
And with a broader view, they say that “the risk of myocarditis after COVID-19 immunization is real, but this low risk must be seen in the context of the overall benefit of vaccine,” both at the individual level and at the population level.
Vaccination prevents serious outcomes up to and including deaths of recipients and “helps reduce the spread of society, reduce the chances of new variants emerging, protect people who are immunocompromised, and ensure that our health care system can continue to care for our society,” Navar and Bonow write.