In a recent study published in the Journal of the American College of Cardiology, researchers compared the prognosis of myocarditis developing after BNT162b2 messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccination with viral myocarditis over six months.

Background

Studies have reported an association of COVID-19 mRNA vaccines with myocarditis globally. The prognostic outcomes of post-vaccination myocarditis are reportedly mild compared to myocarditis acquired otherwise, such as post-influenza infections.

Amid the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, non-pharmaceutical mitigation strategies like social distancing have significantly reduced counts of circulating pathogens capable of inducing myocarditis like the influenza virus. Thus, data for comparing the prognosis of myocarditis cases among COVID-19 mRNA vaccinees and viral infection-associated myocarditis are limited.

About the study

In the present territory-wide retrospective cohort study, researchers examined the probable prognostic differences between individuals diagnosed with myocarditis following BNT162b2 vaccinations and individuals diagnosed with viral illness-associated myocarditis.

Routine healthcare records in Hong Kong’s hospital authority electronic public healthcare database were linked to the health department’s population-based COVID-19 vaccination records for identifying cases of myocarditis post-mRNA COVID-19 vaccinations. The inpatient records and COVID-19 vaccination records were matched based on the pseudo-identification numbers allotted by the health department and hospital authority.

Beginning from the date of Pfizer-BioNTech’s BNT162b2 COVID-19 vaccination rollout in Hong Kong, 6 March 2021, individuals 12 years of age admitted to hospitals with myocarditis in ≤28.0 days of BNT162b2 vaccinations were assessed for being included in the post-BNT162b2- vaccination-myocarditis cohort.

Other individuals diagnosed with myocarditis between 1 January 2000 and 31 December 2019 were assessed for being allotted to the viral illness-associated myocarditis group for comparative evaluation. The diagnosis of myocarditis and the prognostic outcomes were based on the international classification of diseases, ninth clinical modification (ICD-9-CM) codes.

Follow-up assessments were performed from the index date (myocarditis diagnosis date) until the study outcome, death, six-month follow-up period, or 31 March 2022, whichever occurred first. Individuals infected by SARS-CoV-2, based on positive PCR (polymerase chain reaction) reports, during the ongoing episode were excluded from the analysis. The team also excluded cases without increased troponin levels during index hospitalizations and individuals with a history of any investigated outcomes before the respective index dates.

The incidence rates of study outcomes such as any-cause deaths, dilated cardiomyopathy, cardiac failure, post-discharge healthcare utilization, heart transplants, intensive care unit (ICU) admissions, A & E attendance, and subsequent hospitalizations were assessed using multivariable Cox proportional hazard-based modeling, and the adjusted hazard ratios (HR) were calculated. The study covariates adjusted for included age, sex, Charlson comorbidity index scores, previous year’s healthcare use, and cardiovascular medications prescribed in the previous year.

Results

By 31 March 2022, 8,896,843 BNT162b2 vaccine doses were administered to 3,979,103 patients of 12 years and above in Hong Kong. Between 1 January 2000 and 31 December 2019, 1,483 myocarditis cases were documented, of which 119 cases were of post-BNT162b2 vaccination myocarditis. After applying the eligibility criteria, 866 individuals were considered for the final analysis, comprising 104 (12%) patients with post-mRNA COVID-19 vaccination myocarditis and 762.0 (88.0%) patients with viral infection-associated myocarditis. The post-BNT162b2 vaccination myocarditis incidence was estimated as 2.6 among every 100,000 vaccinees.

Among post- BNT162b2 vaccination myocarditis cases, 92% (n=96) of individuals had been administered ≥1.0 prime dose 68 [65%] received double-dose vaccinations), whereas only eight individuals had been administered triple-dose (booster) vaccinations. More men than women comprised both study groups with the exception of elder individuals. Among elders, greater cardiovascular medicine usage, greater healthcare use in the previous year (including hospitalizations, outpatient department consultations, and A&E attendance), and greater comorbidity scores were noted among individuals with post-BNT162b2 vaccination myocarditis.

During six months of following-up, 1.0% (one out of 104 individuals) with post-BNT162b2 vaccination myocarditis and 11% (84 out of 762 individuals) with a viral infection–associated myocarditis died. One dilated cardiomyopathy case and two cases of cardiac failure were reported among BNT162b2 vaccinees with myocarditis, compared to 28 dilated cardiomyopathies and 93 cardiac failure cases among the viral infection–associated myocarditis group individuals, respectively. The post-COVID-19 vaccination myocarditis group demonstrated 92.0% lower death risks (adjusted hazard ratio 0.1).

Similar findings were obtained after restricting the analysis to individuals aged between 18 years and 59 years (adjusted HR 0.1). Confining myocarditis post-mRNA COVID-19 vaccinations to cases occurring within two weeks of receiving BNT162b2 vaccines, the team observed a statistically significant association with a greater number of hospitalizations (adjusted HR 1.8). Increasing the period to 56.0 days, the death reports resembled initial reports (adjusted HR 0.2).

Conclusion

Overall, the study findings showed significantly lesser mortality rates among individuals diagnosed with myocarditis post-COVID-19 mRNA vaccination than individuals with viral infection-associated myocarditis. The prognosis of the iatrogenic health condition might be of lesser severity compared to natural viral infection-associated myocarditis.