- Historical shifts in hospital use (and thereby in disease incidence rates), which is probably during a pandemic, could skew the magnitude of the association.
- 9 However, one case series, published in 2022, of adolescent patients found persistence of radiographic abnormalities at follow-up examinations, which could be cause for concern.
- Other mechanisms have been suggested, yet hard evidence explaining the association is absent.
Rare cases of young men in Israel developing myocarditis quickly after immunisation with the Pfizer-BioNTech mRNA vaccine against SARS-CoV-2 were first reported in April 2021 by foreign news outlets as reported by The Lancet.
Short-term myocarditis
Since then, many observational studies from Asia, Europe, the Middle East, and North America have found COVID-19 mRNA vaccination to be associated with short-term increased risk of myocarditis.
Furthermore, this association has been established using multiple types of analysis, including comparisons of observed-to-expected rates, case-control studies, self-controlled case series, and cohort studies.
In The Lancet, Hui-Lee Wong and colleagues robustly replicate the previous findings using large-scale US health plan claims data.
Notably, the new study uses data from four health plan databases, covering more than 100 million individuals.
Of these, 15 148 369 were aged 18–64 years and registered to have received a COVID-19 mRNA vaccine (53·1% male and 13·0% aged 18–25 years).
Tendency to higher risk
Furthermore, the study supports the previous finding that the association is principally short-term.
Although not significantly different, the study found a tendency towards a higher risk of myocarditis after vaccination with mRNA-1273 in a head-to-head comparison with BNT162b2 (with an adjusted incidence rate ratio of 1·43 [95% CI 0·88–2·34] among men aged 18–25 years).
Despite being both stringent and relevant, the study by Wong and colleagues has some limitations.
Historical shifts in hospital use (and thereby in disease incidence rates), which is probably during a pandemic, could skew the magnitude of the association.
Third, the use of claims databases as the source of study material provides a little specification of the demographic composition of the study population, with no information on the race, ethnicity, or socioeconomic background of the individuals studied.
Rare cases
There are still two major unanswered research questions: firstly, are there any long-term consequences of vaccine-associated myocarditis; and secondly, what is the biological mechanism linking COVID-19 mRNA vaccination to these rare cases of acute myocarditis and pericarditis?
The clinical presentations of myocarditis after COVID-19 mRNA vaccination have been predominantly mild and few patients have required intensive treatment.
However, the patients who followed up had excellent clinical outcomes, suggesting minimal chronic morbidity attributable to vaccine-associated myocarditis.
Other mechanisms have been suggested, yet hard evidence explaining the association is absent.
Future mechanistic studies into potential mechanisms are therefore warranted and could provide valuable insight, leading to even safer COVID-19 mRNA vaccines.
LK reports speaker’s fees from AstraZeneca, Bayer, Boehringer, Novartis, and Novo Nordisk unrelated to the area of work discussed in this Comment.
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Source: The Lancet
