Cardiac Adverse Events Following COVID-19 Vaccination in Patients With Prior Vaccine-Associated Myocarditis
Background: Limited information exists to guide shared clinical decision making on COVID-19 vaccination in persons with a prior history of vaccine-associated myocarditis, pericarditis, or myopericarditis (VAMP). The objective of this retrospective observational case series was to characterize cardiac outcomes within 30 days following receipt of 1 or more COVID-19 vaccinations during 2021 in US service members diagnosed with prior non-COVID-19 VAMP between 1998 and 2019.
Methods: As part of the collaborative public health mission with the Centers for Disease Control and Prevention for enhanced vaccine adverse events surveillance, the Defense Health Agency Immunization Healthcare Division maintains a clinical database of service members and beneficiaries referred for suspected adverse events following immunizations. Cases in this database recorded between January 1, 2003, and February 28, 2022, were reviewed to identify individuals with prior VAMP who received a COVID-19 vaccine in 2021 and developed signs or symptoms suggestive of VAMP within 30 days following COVID-19 vaccination.
Results: Before the COVID-19 pandemic, 431 service members had verified VAMP. Among these 431 patients, 179 had records that confirmed receipt of a COVID-19 vaccine in 2021. Of these 179 patients, 171 (95.5%) were male. Their median age was 39 years (range, 21-67) at the time of COVID-19 vaccination. Most (n = 172; 96.1%) experienced their original VAMP episode after receipt of the live replicating smallpox vaccine. Eleven patients experienced cardiac-suggestive symptoms (chest pain, palpitations, or dyspnea) within 30 days of COVID-19 vaccination. Four patients met the criteria for recurrent VAMP. Three men aged 49, 50, and 55 years developed myocarditis within 3 days of an mRNA COVID-19 vaccine. One 25-year-old man developed pericarditis within 4 days of receiving an mRNA vaccine. All 4 COVID-19 recurrent VAMP cases fully recovered with minimal supportive care within weeks (myocarditis) to months (pericarditis).
Conclusions: As demonstrated by this case series, albeit rare, VAMP may reoccur after COVID-19 vaccination among patients who experienced cardiac injury after smallpox vaccination. The clinical characteristics and course of the 4 recurring cases were mild, appearing similar to the post-COVID-19 VAMP described in individuals without a history of VAMP. More research is warranted on factors that may predispose patients to vaccine-associated cardiac injury and which vaccine platforms or schedules may reduce the risk of recurrence among patients who have experienced these events.
Within 1 month of receipt of any COVID-19 vaccine, 11 individuals had documented symptoms suggesting cardiac involvement, specifically, chest pain, palpitations, or dyspnea. After cardiac evaluation, 4 patients met the criteria for VAMP after COVID-19 vaccination.10,11 Seven patients either did not meet the criteria for VAMP or had alternative causes for their symptoms.
Two men aged 49 and 50 years with a history of vaccine-associated myocarditis following smallpox vaccination (Dryvax and ACAM2000) developed myocarditis 3 days after their second dose of the Moderna vaccine. One of these patients received a Pfizer-BioNTech booster 10 months later with no recurrence of symptoms. A 55-year-old man with a history of vaccine-associated myocarditis following Dryvax vaccination developed myocarditis 2 days after his Pfizer-BioNTech booster. None of the patients who developed post-COVID-19 VAMP reported residual symptoms from their initial VAMP episode, which occurred 12 to 18 years earlier. All were hospitalized briefly for observation and had complete symptom resolution within 6 weeks.
A 25-year-old man developed pericarditis 4 days after his second Pfizer-BioNTech vaccination. His previous ACAM2000 vaccine-associated myocarditis occurred 3 years earlier, with no residual symptoms. Of note, he had a mild COVID-19 infection 78 days before the onset of his pericarditis. After the onset of his COVID-19 vaccine-associated pericarditis, he continued to experience transient bouts of chest pressure and exertional dyspnea that resolved within 7 months of onset.
The median interval between COVID-19 vaccine doses in those who developed post-COVID-19 VAMP was within the recommended mRNA vaccine dosing intervals of 3 to 4 weeks and was consistent with the median mRNA vaccine dosing intervals among the entire cohort.
Due to the small cohort size and other limitations of this study, the suggested rate of cardiac injury in this review (4 cases in 179 persons, or 2.2%) is an imprecise estimate of risk in a small population (95% CI, 0.1%-4.4%). While this rate may seem higher than expected within the general population after COVID-19 vaccination, it is lower than the estimated lifetime risk of recurrent myocarditis from any cause.6,12
