Cardiovasc Prev Pharmacother.  2023 Oct;5(4):134-143. 10.36011/cpp.2023.5.e17.

COVID-19 vaccination–related cardiovascular complications

• Cho JY
• Kim KH

• KMID: 2547304
• DOI: http://doi.org/10.36011/cpp.2023.5.e17

Abstract

The global response to the COVID-19 pandemic has led to rapid vaccine development and distribution. As vaccination efforts continue, concerns have arisen regarding potential adverse events associated with COVID-19 vaccination. This article examines emerging evidence on adverse events, including myocarditis, pericarditis, and thrombotic complications, in relation to COVID-19 vaccination. Reports of myocarditis and pericarditis cases following messenger RNA vaccines have sparked interest, with discussions revolving around potential mechanisms and genetic predispositions. The contrasting findings on pericarditis risk postvaccination highlight the complexity of studying this phenomenon. Thrombotic events, particularly vaccine-induced thrombotic thrombocytopenia, have garnered attention, prompting investigations into antibody responses and mechanisms. This article underscores the importance of ongoing research, collaboration, and data analysis for accurately understanding adverse events. While the COVID-19 vaccination campaign may have ended, it is still vital to maintain vigilance, collect comprehensive data and foster interdisciplinary collaboration to uphold vaccine safety and steer public health strategies in the upcoming period.

Keyword

COVID-19; Vaccination; Cardiovascular diseases; Adverse cardiac events

Figure

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  Fig. 1. COVID-19 vaccination–related cardiovascular complications.

Reference

1. Witberg G, Barda N, Hoss S, Richter I, Wiessman M, Aviv Y, et al. Myocarditis after COVID-19 vaccination in a large health care organization. N Engl J Med. 2021; 385:2132–9.

2. Patone M, Mei XW, Handunnetthi L, Dixon S, Zaccardi F, Shankar-Hari M, et al. Risks of myocarditis, pericarditis, and cardiac arrhythmias associated with COVID-19 vaccination or SARS-CoV-2 infection. Nat Med. 2022; 28:410–22.

3. Cho JY, Kim KH, Lee N, Cho SH, Kim SY, Kim EK, et al. COVID-19 vaccination-related myocarditis: a Korean nationwide study. Eur Heart J. 2023; 44:2234–43.

4. Block JP, Boehmer TK, Forrest CB, Carton TW, Lee GM, Ajani UA, 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; 71:517–23.

5. Oster ME, Shay DK, Su JR, Gee J, Creech CB, Broder KR, et al. Myocarditis cases reported after mRNA-Based COVID-19 vaccination in the US from December 2020 to August 2021. JAMA. 2022; 327:331–40.

6. Fiolet T, Kherabi Y, MacDonald CJ, Ghosn J, Peiffer-Smadja N. Comparing COVID-19 vaccines for their characteristics, efficacy and effectiveness against SARS-CoV-2 and variants of concern: a narrative review. Clin Microbiol Infect. 2022; 28:202–21.

7. Pillay J, Gaudet L, Wingert A, Bialy L, Mackie AS, Paterson DI, et al. Incidence, risk factors, natural history, and hypothesised mechanisms of myocarditis and pericarditis following COVID-19 vaccination: living evidence syntheses and review. BMJ. 2022; 378:e069445.

8. Heymans S, Cooper LT. Myocarditis after COVID-19 mRNA vaccination: clinical observations and potential mechanisms. Nat Rev Cardiol. 2022; 19:75–7.

9. Husby A, Hansen JV, Fosbol E, Thiesson EM, Madsen M, Thomsen RW, et al. SARS-CoV-2 vaccination and myocarditis or myopericarditis: population based cohort study. BMJ. 2021; 375:e068665.

10. Mevorach D, Anis E, Cedar N, Bromberg M, Haas EJ, Nadir E, et al. Myocarditis after BNT162b2 mRNA vaccine against COVID-19 in Israel. N Engl J Med. 2021; 385:2140–9.

11. Bozkurt B, Kamat I, Hotez PJ. Myocarditis with COVID-19 mRNA vaccines. Circulation. 2021; 144:471–84.

12. Diaz GA, Parsons GT, Gering SK, Meier AR, Hutchinson IV, Robicsek A. Myocarditis and pericarditis after vaccination for COVID-19. JAMA. 2021; 326:1210–2.

13. Vdovenko D, Eriksson U. Regulatory role of CD4+ T cells in myocarditis. J Immunol Res. 2018; 2018:4396351.

14. Anderson EJ, Rouphael NG, Widge AT, Jackson LA, Roberts PC, Makhene M, et al. Safety and immunogenicity of SARS-CoV-2 mRNA-1273 vaccine in older adults. N Engl J Med. 2020; 383:2427–38.

15. Hanson PJ, Liu-Fei F, Ng C, Minato TA, Lai C, Hossain AR, et al. Characterization of COVID-19-associated cardiac injury: evidence for a multifactorial disease in an autopsy cohort. Lab Invest. 2022; 102:814–25.

16. Thurner L, Kessel C, Fadle N, Regitz E, Seidel F, Kindermann I, et al. IL-1RA antibodies in myocarditis after SARS-CoV-2 vaccination. N Engl J Med. 2022; 387:1524–7.

17. Lai FT, Li X, Peng K, Huang L, Ip P, Tong X, et al. Carditis after COVID-19 vaccination with a messenger RNA vaccine and an inactivated virus vaccine: a case-control study. Ann Intern Med. 2022; 175:362–70.

18. Cassimatis DC, Atwood JE, Engler RM, Linz PE, Grabenstein JD, Vernalis MN. Smallpox vaccination and myopericarditis: a clinical review. J Am Coll Cardiol. 2004; 43:1503–10.

19. Curcio R, Gandolfo V, Alcidi R, Giacomino L, Campanella T, Casarola G, et al. Vaccine-induced massive pulmonary embolism and thrombocytopenia following a single dose of Janssen Ad26.COV2.S vaccination. Int J Infect Dis. 2022; 116:154–6.

20. Schultz NH, Sorvoll IH, Michelsen AE, Munthe LA, Lund-Johansen F, Ahlen MT, et al. Thrombosis and thrombocytopenia after ChAdOx1 nCoV-19 vaccination. N Engl J Med. 2021; 384:2124–30.

21. Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic thrombocytopenia after ChAdOx1 nCov-19 vaccination. N Engl J Med. 2021; 384:2092–101.

22. Scully M, Singh D, Lown R, Poles A, Solomon T, Levi M, et al. Pathologic antibodies to platelet factor 4 after ChAdOx1 nCoV-19 vaccination. N Engl J Med. 2021; 384:2202–11.

23. See I, Su JR, Lale A, Woo EJ, Guh AY, Shimabukuro TT, et al. US case reports of cerebral venous sinus thrombosis with thrombocytopenia after Ad26.COV2.S vaccination, March 2 to April 21, 2021. JAMA. 2021; 325:2448–56.

24. Al-Rasbi S, Al-Maqbali JS, Al-Farsi R, Al Shukaili MA, Al-Riyami MH, Al Falahi Z, et al. Myocarditis, pulmonary hemorrhage, and extensive myositis with rhabdomyolysis 12 days after first dose of Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine: a case report. Am J Case Rep. 2022; 23:e934399.

25. Jabagi MJ, Botton J, Bertrand M, Weill A, Farrington P, Zureik M, et al. Myocardial infarction, stroke, and pulmonary embolism after BNT162b2 mRNA COVID-19 vaccine in people aged 75 years or older. JAMA. 2022; 327:80–2.

26. Bocchino M, Rea G, Buonocore A, Lieto R, Mazzocca A, Di Domenico A, et al. Combination of acute exacerbation of idiopathic nonspecific interstitial pneumonia and pulmonary embolism after booster anti-COVID-19 vaccination. Respir Med Case Rep. 2022; 38:101674.

27. Alshammari F, Abuzied Y, Korairi A, Alajlan M, Alzomia M, AlSheef M. Bullous pemphigoid after second dose of mRNA- (Pfizer-BioNTech) COVID-19 vaccine: a case report. Ann Med Surg (Lond). 2022; 75:103420.

28. Kyaw H, Shajahan S, Gulati A, Synn S, Khurana S, Nazar N, et al. COVID-19 mRNA vaccine-associated myocarditis. Cureus. 2022; 14:e21009.

29. Huynh A, Kelton JG, Arnold DM, Daka M, Nazy I. Antibody epitopes in vaccine-induced immune thrombotic thrombocytopaenia. Nature. 2021; 596:565–9.

30. Greinacher A, Selleng K, Palankar R, Wesche J, Handtke S, Wolff M, et al. Insights in ChAdOx1 nCoV-19 vaccine-induced immune thrombotic thrombocytopenia. Blood. 2021; 138:2256–68.

31. Baker AT, Boyd RJ, Sarkar D, Teijeira-Crespo A, Chan CK, Bates E, et al. ChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome. Sci Adv. 2021; 7:eabl8213.

32. Korea Disease Control and Prevention Agency (KDCA). COVID-19 vaccination adverse event status report (week 130). KDCA; 2023.

33. Hippisley-Cox J, Patone M, Mei XW, Saatci D, Dixon S, Khunti K, et al. Risk of thrombocytopenia and thromboembolism after COVID-19 vaccination and SARS-CoV-2 positive testing: self-controlled case series study. BMJ. 2021; 374:n1931.

34. Cari L, Fiore P, Naghavi Alhosseini M, Sava G, Nocentini G. Blood clots and bleeding events following BNT162b2 and ChAdOx1 nCoV-19 vaccine: an analysis of European data. J Autoimmun. 2021; 122:102685.

35. Cari L, Alhosseini MN, Fiore P, Pierno S, Pacor S, Bergamo A, et al. Cardiovascular, neurological, and pulmonary events following vaccination with the BNT162b2, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines: an analysis of European data. J Autoimmun. 2021; 125:102742.

36. Klein NP, Lewis N, Goddard K, Fireman B, Zerbo O, Hanson KE, et al. Surveillance for adverse events after COVID-19 mRNA vaccination. JAMA. 2021; 326:1390–9.

37. Simpson CR, Shi T, Vasileiou E, Katikireddi SV, Kerr S, Moore E, et al. First-dose ChAdOx1 and BNT162b2 COVID-19 vaccines and thrombocytopenic, thromboembolic and hemorrhagic events in Scotland. Nat Med. 2021; 27:1290–7.

38. Houghton DE, Wysokinski W, Casanegra AI, Padrnos LJ, Shah S, Wysokinska E, et al. Risk of venous thromboembolism after COVID-19 vaccination. J Thromb Haemost. 2022; 20:1638–44.

39. Burn E, Roel E, Pistillo A, Fernandez-Bertolin S, Aragon M, Raventos B, et al. Thrombosis and thrombocytopenia after vaccination against and infection with SARS-CoV-2 in Catalonia, Spain. Nat Commun. 2022; 13:7169.

40. Nicholson M, Goubran H, Chan N, Siegal D. No apparent association between mRNA COVID-19 vaccination and venous thromboembolism. Blood Rev. 2022; 56:100970.

41. Pottegard A, Lund LC, Karlstad O, Dahl J, Andersen M, Hallas J, et al. Arterial events, venous thromboembolism, thrombocytopenia, and bleeding after vaccination with Oxford-AstraZeneca ChAdOx1-S in Denmark and Norway: population based cohort study. BMJ. 2021; 373:n1114.

42. Barda N, Dagan N, Ben-Shlomo Y, Kepten E, Waxman J, Ohana R, et al. Safety of the BNT162b2 mRNA COVID-19 vaccine in a nationwide setting. N Engl J Med. 2021; 385:1078–90.

43. Health Insurance Review and Assessment Service (HIRA). September 29, "World Heart Day": heart diseases by the numbers [Internet]. HIRA; 2021 [cited 2023 Sep 1]. Available from: https://www.hira.or.kr/bbsDummy.do?pgmid=HIRAA020041000100&brdScnBltNo=4&brdBltNo=10428&pageIndex=1#none.

44. Tajstra M, Jaroszewicz J, Gąsior M. Acute coronary tree thrombosis after vaccination for COVID-19. JACC Cardiovasc Interv. 2021; 14:e103–4.

45. Lim Y, Kim MC, Kim KH, Jeong IS, Cho YS, Choi YD, et al. Case report: acute fulminant myocarditis and cardiogenic shock after messenger RNA coronavirus disease 2019 vaccination requiring extracorporeal cardiopulmonary resuscitation. Front Cardiovasc Med. 2021; 8:758996.

46. van den Hoogen P, van den Akker F, Deddens JC, Sluijter JP. Heart failure in chronic myocarditis: a role for microRNAs? Curr Genomics. 2015; 16:88–94.