The most common serious adverse event related to mRNA COVID-19 vaccines in young people is myocarditis. The prognosis of vaccine-related myocarditis appears to be favourable compared to viral myocarditis, with data from Hong Kong suggesting a 92% lower mortality risk [
28]. The clinical course for most cases is mild, although abnormalities were still present in 54% of patients followed for at least 90 days since onset in a US study, with 68% cleared to return to physical activity [
29]. Whilst many studies of the rates of myocarditis following COVID-19 vaccination provide population-wide estimates, the risks are highly dependent on age, gender, previous doses of vaccination, and possibly interval and dose of vaccine administered. Risks for females are only slightly elevated compared to expected rates and are higher in adolescent and young females than older females, with a risk around 2 to 3 per 100,000 doses [
30‐
32]. The risk in males is higher, with a significantly increased risk between the ages of 12 and 30 which is highest after the second or third dose of vaccine. Rates also appear to be higher following mRNA-1273, although this has not been as widely used in children [
30]. For adolescent males, rates after the second dose of BNT162b2 range from 6.7 to 15 per 100,000 [
30‐
32]. There are limited data following third doses, but a Canadian study estimated a rate of 7 per 100,000 (observed to expected case ratio (OER) of 139.8 (95% CI 28.8–408.6) which was higher than following the second dose (OER 134.29, 95%CI 61.4 to 254) [
31]. Data is more scarce for children aged under 12 years, but myocarditis appears to be less common in this age group, with one systematic review estimating an incidence of 1.8 per million [
33]. It is unclear whether lower rates are a function of lower biological risk, a lower dose of vaccine, and/or reduced ascertainment in younger children. It is also unclear how previous antigen exposure through infection impacts risk, as most studies assume an infection naive cohort and do not address prior exposure from infection.
Many studies which attempt to compare the rates of myocarditis after vaccination versus COVID-19 infection overestimate the rates following infection, as the denominator is comprised only of cases detected via testing. It is well known that most infections of COVID-19 go undetected due to the low symptom burden, and so the true myocarditis rate following infection is likely to be several times smaller than estimated in these studies, by a factor of 5 to 10 [
34].