糖心vlog

To the Editor The case series by Dr Oster and colleagues described adverse event reports of myocarditis following SARS-CoV-2 messenger RNA (mRNA) vaccination from the Vaccine Adverse Event Reporting System (VAERS).¹ The authors purported to answer the question 鈥淲hat is the risk of myocarditis after an RNA-based COVID-19 vaccination in the US?鈥� However, it is not possible to calculate risk or incidence rates from passive surveillance. Due to reporting regulations and limitations of passive surveillance, VAERS reports are a biased subset of events.

A reporting rate that is higher than an expected or background rate can, at best, be interpreted as a signal to investigate. Many factors introduce bias, including some intrinsic to passive surveillance (eg, underreporting and reporting bias) and others extrinsic to passive surveillance (eg, detection bias). Therefore, VAERS reports should not be considered a valid substitute for incidence cases. Despite these limitations, Oster and colleagues concluded that 鈥渢he risk of myocarditis after receiving mRNA-based COVID-19 vaccines was increased across multiple age and sex strata鈥�.鈥�¹

Retrospective cohort studies about mRNA COVID-19 vaccinations based on health care records have reported incidence rates of vaccine-associated myocarditis well above VAERS-reported rates, with the highest incidence among young male individuals after the second dose of vaccine. The incidence rate of a confirmed myocarditis diagnosis, within 7 days of a second mRNA vaccine dose, was 565.9 events per 1 million person-years among male individuals aged 12 to 39 years.² Israeli studies, which used a combination of active and passive surveillance and a 30-day risk window, reported the risk of myocarditis after the second mRNA COVID-19 vaccine dose as 80.9 per 1 million in male individuals aged 12 to 15 years, 150.7 per 1 million in male individuals aged 16 to 19 years, and 108.6 per 1 million in male individuals aged 20 to 24 years.^3,4

Studies of myocarditis following smallpox vaccination suggest that these retrospective studies may still have underestimated the risk of mRNA vaccine-associated myocarditis, perhaps substantially. A prospective study reported a substantially higher incidence of confirmed myocarditis after smallpox vaccination (463 cases per 100鈥�000 persons) compared with the incidence rate based on a combination of active, passive, and sentinel surveillance (16.11 cases per 100鈥�000 persons).⁵ Furthermore, only 2 of the 5 men diagnosed as having incident myocarditis in the prospective study of smallpox vaccination had sought medical care outside of the study protocol, and almost 3% of participants (2868 cases per 100鈥�000) met the study definition for possible subclinical myocarditis. Given the heterogeneity in severity and presentation of myocarditis, absent prospective cohort studies with long-term follow-up, the risk of myocarditis after SARS-CoV-2 vaccination and its implications remain unknown.

Corresponding Author: Sheila R. Weiss, PhD, Exponent, 1150 Connecticut Ave NW, Ste 1100, Washington, DC 20036 (sweiss@exponent.com).

Conflict of Interest Disclosures: Dr Weiss reported consulting work with Pfizer and AstraZeneca.