Original Research

Cardiac Adverse Events Following COVID-19 Vaccination in Patients With Prior Vaccine-Associated Myocarditis

Fed Pract. 2023 January;40(1):6-10 | doi:10.12788/fp.0354

Author(s):

Jay R. Montgomery, MD

Donna L. Hoffman, MSN

Margaret A. Ryan, MD

Rachel U. Lee, MD

Laurie A. Housel, MSN

Renata J. Engler, MD

Limone C. Collins, MD

John E. Atwood, MD

Leslie T. Cooper, MD

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.

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References

2. Engler RJ, Nelson MR, Collins LC Jr, et al. A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination. PLoS One. 2015;10(3):e0118283. doi:10.1371/journal.pone.0118283

3. Faix DJ, Gordon DM, Perry LN, et al. Prospective safety surveillance study of ACAM2000 smallpox vaccine in deploying military personnel. Vaccine. 2020;38(46):7323-7330. doi:10.1016/j.vaccine.2020.09.037

4. Montgomery J, Ryan M, Engler R, et al. Myocarditis following immunization with mRNA COVID-19 vaccines in members of the US military. JAMA Cardiol. 2021;6(10):1202-1206. doi:10.1001/jamacardio.2021.2833

5. Witberg G, Barda N, Hoss S, et al. Myocarditis after Covid-19 vaccination in a large health care organization. N Engl J Med. 2021;385(23):2132-2139. doi:10.1056/NEJMoa2110737

6. Oster ME, Shay DK, Su JR, et al. Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from December 2020 to August 2021. JAMA. 2022;327(4):331-340. doi:10.1001/jama.2021.24110

7. Su JR, McNeil MM, Welsh KJ, et al. Myopericarditis after vaccination, Vaccine Adverse Event Reporting System (VAERS), 1990-2018. Vaccine. 2021;39(5):839-845. doi:10.1016/j.vaccine.2020.12.046

8. Mei R, Raschi E, Forcesi E, Diemberger I, De Ponti F, Poluzzi E. Myocarditis and pericarditis after immunization: gaining insights through the Vaccine Adverse Event Reporting System. Int J Cardiol. 2018;273:183-186. doi:10.1016/j.ijcard.2018.09.054

9. Centers for Disease Control and Prevention (CDC). Update: cardiac-related events during the civilian smallpox vaccination program—United States, 2003. MMWR Morb Mortal Wkly Rep. 2003;52(21):492-496.

10. Gargano JW, Wallace M, Hadler SC, et al. Use of mRNA COVID-19 vaccine after reports of myocarditis among vaccine recipients: update from the Advisory Committee on Immunization Practices—United States, June 2021. MMWR Morb Mortal Wkly Rep. 2021;70(27):977-982. doi:10.15585/mmwr.mm7027e2

11. Sexson Tejtel SK, Munoz FM, Al-Ammouri I, et al. Myocarditis and pericarditis: case definition and guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. 2022;40(10):1499-1511. doi:10.1016/j.vaccine.2021.11.074

12. Sagar S, Liu PP, Cooper LT Jr. Myocarditis. Lancet. 2012;379(9817):738-747. doi:10.1016/S0140-6736(11) 60648-X

13. Heymans S, Cooper LT. Myocarditis after COVID-19 mRNA vaccination: clinical observations and potential mechanisms. Nat Rev Cardiol. 2022;19(2):75-77. doi:10.1038/s41569-021-00662-w

14. Cohen JI, Hohman P, Fulton R, et al. Kinetics of serum cytokines after primary or repeat vaccination with the smallpox vaccine. J Infect Dis. 2010;201(8):1183-1191. doi:10.1086/651453

15. Minocha PK, Better D, Singh RK, Hoque T. Recurrence of acute myocarditis temporally associated with receipt of the mRNA COVID-19 vaccine in an adolescent male. J Pediatr. 2021;238:321-323. doi:10.1016/j.jpeds.2021.06.035

16. Umei TC, Kishino Y, Watanabe K, et al. Recurrence of myopericarditis following mRNA COVID-19 vaccination in a male adolescent. CJC Open. 2022;4(3):350-352. doi:10.1016/j.cjco.2021.12.002

17. Pasha MA, Isaac S, Khan Z. Recurrent myocarditis following COVID-19 infection and the mRNA vaccine. Cureus. 2022;14(7):e26650. doi:10.7759/cureus.26650

18. Block JP, Boehmer TK, Forrest CB, et al. Cardiac complications after SARS-CoV-2 infection and mRNA COVID-19 vaccination—PCORnet, United States, January 2021-January 2022. MMWR Morb Mortal Wkly Rep. 2022;71(14):517-523. Published 2022 Apr 8. doi:10.15585/mmwr.mm7114e1

Vaccinations have substantially reduced morbidity and mortality from many infectious diseases. Despite the clear value of vaccinations in public health, efforts to better understand adverse events (AEs) following immunization are important to sustain public trust and vaccine confidence. Noninfectious inflammation of the heart may manifest as myocarditis or pericarditis, or occasionally, with shared signs and symptoms of each, as myopericarditis. This is a rare AE following some immunizations. Vaccine-associated myocarditis, pericarditis, or myopericarditis (VAMP) has been most clearly associated with smallpox vaccines and mRNA COVID-19 vaccines.^1-6 Although extremely rare, VAMP also has been associated with other vaccines.^7,8 Limited information exists to guide shared clinical decision making on COVID-19 vaccination in persons with a history of VAMP. It is unknown whether individuals with a history of VAMP are at higher risk for developing a recurrence or experiencing a more severe outcome following COVID-19 vaccination.

Methods

As part of the collaborative public health mission with the Centers for Disease Control and Prevention (CDC) for enhanced vaccine AE surveillance, the Defense Health Agency Immunization Healthcare Division (IHD) maintains a clinical database of service members and beneficiaries referred for suspected AEs following immunizations. A review of all AEs following immunization cases in this database from January 1, 2003, through February 28, 2022, identified individuals meeting the following criteria: (a) VAMP prior to receipt of COVID-19 vaccine; (b) receipt of COVID-19 vaccine in 2021; and (c) medical documentation in available electronic health records sufficient to describe health status at least 30 days following COVID-19 vaccination.⁹ If medical entries suggested cardiac symptoms following a COVID-19 vaccine, additional information was sought to verify VAMP based on current published criteria.^10,11 Both the initial VAMP cases and the suspected COVID-19 VAMP cases were adjudicated by a team of vaccine experts and specialists in immunology, cardiology, and preventive medicine.

This retrospective review was approved and conducted in accordance with the Walter Reed National Military Medical Center Institutional Review Board protocol #20664. All individuals with recurrent VAMP consented to share their health records and clinical details.

Results

Among 9260 cases in the IHD database, 431 met the case definition for VAMP.

Within this cohort, 179 individuals had records available that confirmed receipt of a COVID-19 vaccine in 2021 and described their health status for at least 30 days after vaccination (Figure). Vaccines associated with the initial VAMP episode included 172 smallpox (64 Dryvax and 108 ACAM2000), 3 influenza, 1 Tdap, 1 anthrax, and 2 multiple vaccines. Subsequent COVID-19 vaccines received included 95 Pfizer-BioNTech, 71 Moderna, and 13 Janssen. Thirty-six patients also received mRNA vaccine boosters.

Among the 179 patients included in this analysis, 171 (96%) were male. Their median age was 39 years at the time of COVID-19 vaccination.

The Table describes the cohort’s history of VAMP and subsequent experience with COVID-19 vaccination. Prior VAMP presentations included 99 cases of myocarditis, 39 cases of pericarditis, and 41 cases showing mixed features of myocarditis and pericarditis (myopericarditis).

References

1. Decker MD, Garman PM, Hughes H, et al. Enhanced safety surveillance study of ACAM2000 smallpox vaccine among US military service members. Vaccine. 2021;39(39):5541-5547. doi:10.1016/j.vaccine.2021.08.041

2. Engler RJ, Nelson MR, Collins LC Jr, et al. A prospective study of the incidence of myocarditis/pericarditis and new onset cardiac symptoms following smallpox and influenza vaccination. PLoS One. 2015;10(3):e0118283. doi:10.1371/journal.pone.0118283

3. Faix DJ, Gordon DM, Perry LN, et al. Prospective safety surveillance study of ACAM2000 smallpox vaccine in deploying military personnel. Vaccine. 2020;38(46):7323-7330. doi:10.1016/j.vaccine.2020.09.037

4. Montgomery J, Ryan M, Engler R, et al. Myocarditis following immunization with mRNA COVID-19 vaccines in members of the US military. JAMA Cardiol. 2021;6(10):1202-1206. doi:10.1001/jamacardio.2021.2833

5. Witberg G, Barda N, Hoss S, et al. Myocarditis after Covid-19 vaccination in a large health care organization. N Engl J Med. 2021;385(23):2132-2139. doi:10.1056/NEJMoa2110737

6. Oster ME, Shay DK, Su JR, et al. Myocarditis cases reported after mRNA-based COVID-19 vaccination in the US from December 2020 to August 2021. JAMA. 2022;327(4):331-340. doi:10.1001/jama.2021.24110

7. Su JR, McNeil MM, Welsh KJ, et al. Myopericarditis after vaccination, Vaccine Adverse Event Reporting System (VAERS), 1990-2018. Vaccine. 2021;39(5):839-845. doi:10.1016/j.vaccine.2020.12.046

8. Mei R, Raschi E, Forcesi E, Diemberger I, De Ponti F, Poluzzi E. Myocarditis and pericarditis after immunization: gaining insights through the Vaccine Adverse Event Reporting System. Int J Cardiol. 2018;273:183-186. doi:10.1016/j.ijcard.2018.09.054

9. Centers for Disease Control and Prevention (CDC). Update: cardiac-related events during the civilian smallpox vaccination program—United States, 2003. MMWR Morb Mortal Wkly Rep. 2003;52(21):492-496.

10. Gargano JW, Wallace M, Hadler SC, et al. Use of mRNA COVID-19 vaccine after reports of myocarditis among vaccine recipients: update from the Advisory Committee on Immunization Practices—United States, June 2021. MMWR Morb Mortal Wkly Rep. 2021;70(27):977-982. doi:10.15585/mmwr.mm7027e2

11. Sexson Tejtel SK, Munoz FM, Al-Ammouri I, et al. Myocarditis and pericarditis: case definition and guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine. 2022;40(10):1499-1511. doi:10.1016/j.vaccine.2021.11.074

12. Sagar S, Liu PP, Cooper LT Jr. Myocarditis. Lancet. 2012;379(9817):738-747. doi:10.1016/S0140-6736(11) 60648-X

13. Heymans S, Cooper LT. Myocarditis after COVID-19 mRNA vaccination: clinical observations and potential mechanisms. Nat Rev Cardiol. 2022;19(2):75-77. doi:10.1038/s41569-021-00662-w

14. Cohen JI, Hohman P, Fulton R, et al. Kinetics of serum cytokines after primary or repeat vaccination with the smallpox vaccine. J Infect Dis. 2010;201(8):1183-1191. doi:10.1086/651453

15. Minocha PK, Better D, Singh RK, Hoque T. Recurrence of acute myocarditis temporally associated with receipt of the mRNA COVID-19 vaccine in an adolescent male. J Pediatr. 2021;238:321-323. doi:10.1016/j.jpeds.2021.06.035

16. Umei TC, Kishino Y, Watanabe K, et al. Recurrence of myopericarditis following mRNA COVID-19 vaccination in a male adolescent. CJC Open. 2022;4(3):350-352. doi:10.1016/j.cjco.2021.12.002

17. Pasha MA, Isaac S, Khan Z. Recurrent myocarditis following COVID-19 infection and the mRNA vaccine. Cureus. 2022;14(7):e26650. doi:10.7759/cureus.26650

18. Block JP, Boehmer TK, Forrest CB, et al. Cardiac complications after SARS-CoV-2 infection and mRNA COVID-19 vaccination—PCORnet, United States, January 2021-January 2022. MMWR Morb Mortal Wkly Rep. 2022;71(14):517-523. Published 2022 Apr 8. doi:10.15585/mmwr.mm7114e1

Cardiac Adverse Events Following COVID-19 Vaccination in Patients With Prior Vaccine-Associated Myocarditis

References

Methods

Results

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