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INFECTIOUS DISEASE
Vaccination versus Active Infection: A Comparison of the Cardiovascular Risks
Medical writer: Christy Leung | Last updated: 26 August 2022 | In: COVID-19, Cardiovascular, SARS-CoV2, Infectious Disease
Article Keywords
COVID-19, SARS-CoV-2, vaccination, Infectious Disease, cardiovascular
Inflammation and homeostasis disruption, from either coronavirus disease 2019 (COVID-19) infection and vaccination, can give rise to cardiovascular pathology.11. Del Prete A, et al. Card Electrophysiol Clin. 2022;14(1):29-39. doi: 10.1016/j.ccep.2021.10.004 Transmitted by the SARS-CoV-2 virus, COVID-19 has been a global public health issue since 2020. Infection was predominantly caused by the wild-type strain and Alpha variant in 2020, followed by the Delta and Omicron variants in 2021 and 2022 respectively.2,32. Brainard J, et al. Infection. 2022:1-8. doi: 10.1007/s15010-022-01787-x.
3. Yale Medicine. Available online. https://www.yalemedicine.org/news/covid-19-variants-of-concern-omicron. Last accessed: 18 July 2022. At the same time, COVID-19 vaccines were invented; the inactivated CZ02 and mRNA BNT162b2 vaccines are available in Hong Kong. Cardiovascular events have been documented both post-infection and post-vaccination. The post-infection cardiovascular complications include acute myocardial infarction (MI), heart failure, arrhythmia, thromboembolism, and multisystem inflammatory syndrome (MIS) with cardiovascular manifestation, aside from myocarditis and pericarditis.11. Del Prete A, et al. Card Electrophysiol Clin. 2022;14(1):29-39. doi: 10.1016/j.ccep.2021.10.004. Myocardial infarction can be subdivided into Types 1 (by plaque instability) and 2 (myocardial oxygen supply-demand imbalance).44. Sabatine MS, et al. JAMA Cardiol. 2021;6(7):781. doi:10.1001/jamacardio.2021.0693. On the other hand, myocarditis and pericarditis are known post-vaccination complications.55. Block JP, et al. MMWR Morb Mortal Wkly RXep. 2022;71:517-23. doi:10.15585/mmwr.mm7114e1. The mRNA-1273 vaccination is associated with increased thromboembolism risk, but will be omitted in this article since it is not available locally.66. Mahgoub AE, et al. Cureus. 2022;14(2):e22179. doi:10.7759/cureus.22179.
Post-active COVID-19 cardiovascular complications may be explained by two mechanisms: hyperinflammatory state and renin-angiotensin system (RAS) dysregulation. The former affects both the cardiac and vascular components — proinflammatory cytokine secretion upon SARS-CoV-2 myocardial entry causes direct cell damage in myocarditis, while viral invasion at coronary artery endothelial cells triggers atherosclerotic plaque instability and subsequently rupture, causing Type 1 MI.11. Del Prete A, et al. Card Electrophysiol Clin. 2022;14(1):29-39. doi: 10.1016/j.ccep.2021.10.004 Meanwhile, RAS dysregulation is reflected by changes in the angiotensin-converting enzyme 2 (ACE2) receptor. Such receptors are omnipresent in the human body, for instance in the vascular endothelium, respiratory tract, myocardium, kidneys, and pancreas.1,71. Del Prete A, et al. Card Electrophysiol Clin. 2022;14(1):29-39. doi: 10.1016/j.ccep.2021.10.004.
7. Bhattarai A, et al. J Phys Chem Lett. 2021;12(20):4814-22. doi: 10.1021/acs.jpclett.1c01064. Viral entry via ACE2 receptors and subsequent intracellular replication not only damages host cells but also downregulates ACE2 receptor expression.11. Del Prete A, et al. Card Electrophysiol Clin. 2022;14(1):29-39. doi: 10.1016/j.ccep.2021.10.004 Reduced ACE2 (receptor) – Angiotensin II (Ang II) (ligand) binding implies unopposed Ang II effects, namely vasoconstriction, increased vascular permeability, and endothelial damage, altogether accounting for organ damage in MIS. The mechanism of post-vaccination myocarditis and pericarditis is less understood but postulated to be of autoimmune or hyperimmune causes.88. Pillay J, et al. BMJ. 2022; 378. doi: 10.1136/bmj-2021-069445. There are also isolated case reports of post-vaccination myocarditis as a result of accidental intravenous injection.9,109. Kadkhoda K. Vaccine. 2022;40(3):406-7.
10. Li C, et al. Clin Infect Dis. 2022;74(11):1933-50.
The diagnosis of cardiovascular complications follows a clinical-laboratory-radiological approach, in which the latter two are reflected by an elevated high-sensitivity troponin I (hs-TnI) level and myocardial oedema on cardiac magnetic resonance imaging respectively.11,1211. Madjid M, et al. JAMA Cardiol. 2020;5(7):831-40. doi:10.1001/jamacardio.2020.1286.
12. Tijmes FS, et al. Radiology: Cardiothoracic Imaging. 2021;3(6). doi: 10.1148/ryct.210252
Despite the fact that both active infection and vaccination lead to cardiovascular complications, these two events differ in incidence rate. According to a study by Barda et al, the risk ratio of myocarditis post-vaccination (3.24, 95% CI 1.55-12.44) is lower than that following infection (18.28, 95% CI 3.95-25.12).1313. Barda N, et al. N Engl J Med. 2021;385:1078-90. doi: 10.1056/NEJMoa2110475. Moreover, active infection but not COVID-19 vaccination was associated with increased risks in other cardiovascular events, namely arrhythmia, thromboembolism (deep vein thrombosis and pulmonary embolism), and acute myocardial infarction, reflected by positive risk difference values.1313. Barda N, et al. N Engl J Med. 2021;385:1078-90. doi: 10.1056/NEJMoa2110475. High-risk groups for post-vaccination myocarditis include adolescent and young adult males post-second dose, and those who have had more severe infections.14,1514. Husby A & Køber L. Lancet. 2022;389(10342):2168-9. doi:10.1016/S0140-6736(22)00842-X
15. Nature. Available online. https://www.nature.com/articles/d41586-022-00403-0. Last accessed: 18 July 2022. Age was not found to be a predictor for post-infection cardiovascular events.1515. Nature. Available online. https://www.nature.com/articles/d41586-022-00403-0. Last accessed: 18 July 2022. Severe COVID-19 patients are more likely to include those unvaccinated.1616. McMenamin ME, et al. Lancet Infect Dis. 2022. doi:10.1016/S1473-3099(22)00345-0.
Both active COVID-19 infection and vaccination bring about cardiovascular risks. However, active SARS-CoV-2 infections are more sinister and with a higher incidence of cardiovascular events, especially in those with more severe disease and when compared to COVID-19 vaccines. Vaccinations therefore should be recommended to minimise the risk of severe cardiovascular complications. Additional precautionary measures can be taken, including practicing good personal hygiene, complying with quarantine restrictions to avoid active infection, and waiting for at least 30 days between two doses of COVID-19 vaccination to minimise post-vaccination risks.88. Pillay J, et al. BMJ. 2022; 378. doi: 10.1136/bmj-2021-069445.
Reference
- Del Prete A, et al. Card Electrophysiol Clin. 2022;14(1):29-39. doi: 1016/j.ccep.2021.10.004.
- Brainard J, et al. Infection. 2022:1-8. doi: 10.1007/s15010-022-01787-x.
- Yale Medicine. Available online. https://www.yalemedicine.org/news/covid-19-variants-of-concern-omicron. Last accessed: 18 July 2022.
- Sabatine MS, et al. JAMA Cardiol. 2021;6(7):781. doi:10.1001/jamacardio.2021.0693.
- Block JP, et al. MMWR Morb Mortal Wkly RXep. 2022;71:517-23. doi:15585/mmwr.mm7114e1.
- Mahgoub AE, et al. Cureus. 2022;14(2):e22179. doi:10.7759/cureus.22179.
- Bhattarai A, et al. J Phys Chem Lett. 2021;12(20):4814-22. doi: 1021/acs.jpclett.1c01064.
- Pillay J, et al. BMJ. 2022; doi: 10.1136/bmj-2021-069445.
- Kadkhoda K. Vaccine. 2022;40(3):406-7.
- Li C, et al. Clin Infect Dis. 2022;74(11):1933-50.
- Madjid M, et al. JAMA Cardiol. 2020;5(7):831-40. doi:10.1001/jamacardio.2020.1286.
- Tijmes FS, et al. Radiology: Cardiothoracic Imaging. 2021;3(6). doi: 1148/ryct.210252.
- Barda N, et al. N Engl J Med. 2021;385:1078-90. doi:1056/NEJMoa2110475.
- Husby A & Køber L. Lancet. 2022;389(10342):2168-9. doi:1016/S0140-6736(22)00842-X.
- Nature. Available online. https://www.nature.com/articles/d41586-022-00403-0. Last accessed: 18 July 2022.
- McMenamin ME, et al. Lancet Infect Dis. 2022. doi:1016/S1473-3099(22)00345-0.
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This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).
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