Incidence, risk factors, natural history, and hypothesised mechanisms of myocarditis and pericarditis following covid-19 vaccination: living evidence syntheses and review.
Level 3 - non-randomized controlled study
Systematic review of observational cohorts and surveillance data rather than randomized trials
PubMed 35830976 · doi:10.1136/bmj-2021-069445
What was done
A living systematic review and evidence synthesis was conducted searching Medline, Embase, Cochrane Library, reference lists, and grey literature from October 2020 through January 2022. Large (>10,000 participants), population-based, or multisite observational and surveillance studies were evaluated for incidence and risk factors using modified Joanna Briggs Institute tools and GRADE certainty ratings. Case series (n≥5) were analyzed for clinical presentation, short-term course, and longer-term outcomes, alongside primary studies, opinions, letters, and reviews evaluating hypothesized mechanisms.
What was found
46 studies were included (14 on incidence, 7 on risk factors, 11 on characteristics and short-term course, 3 on longer-term outcomes, and 21 on mechanisms). Myocarditis incidence after mRNA vaccines was highest in males aged 12-17 years (50-139 cases per million; low certainty) and 18-29 years (28-147 per million; moderate certainty). In children aged 5-11 years and females aged 18-29 years, incidence after BNT162b2 was fewer than 20 cases per million (low certainty). Incidence after a third dose had very low certainty evidence. For individuals aged 18-29 years, incidence was probably higher after mRNA-1273 compared with BNT162b2 (moderate certainty). An interdose interval of ≥31 days (or ≥56 days in males aged 18-29 years) was associated with lower incidence than ≤30 days (low certainty). Most myocarditis cases in adolescents and adults involved males (>90%) with median age 20-30 years and symptom onset two to four days after dose two (71-100%). Most were hospitalized (≥84%) for two to four days. Three case series with three-month follow-up (n=38) suggested persistent echocardiogram abnormalities, ongoing symptoms, medication needs, or activity restrictions in >50% of patients. Sixteen hypothesized mechanisms had little direct supporting or refuting evidence.
Why it matters
This review synthesizes global evidence demonstrating that adolescent and young adult males have the highest risk of post-mRNA vaccine myocarditis, and that extended dosing intervals and product selection may mitigate this risk.
Limits
Certainty of evidence was low or very low for children aged 5-11 years, third doses, and longer-term outcomes. Long-term follow-up was limited to only three case series totaling 38 patients. Data on clinical risk factors and pericarditis were very limited, and the 16 hypothesized mechanisms lacked direct empirical evidence.
Cited by
- context COVID-19 vaccination caused myocarditis in young people at a rate of 1 in 5,000 to 1 in 10,000.