A narrative review of coronavirus (COVID-19) vaccination and its implication in the development of coronary artery disease: an Indian perspective

Dear Editor,

In the wake of the post-pandemic era, the occurrence of sudden cardiac deaths has gained considerable attention, spreading through public discourse like wildfire, driven in part by media coverage. A direct or indirect connection has been forged in the collective consciousness, implicating vaccines as a potential cause. The primary objective of this review is to investigate this issue rigorously, aiming to discern whether there is any substantive link that can elucidate the notable increase in sudden cardiac deaths among the Indian populace in recent times.

Ironically, the most recent epidemiological study assessing the burden of cardiovascular diseases and the incidence of sudden cardiac death within the Indian population was published back in 2016, strikingly absent of any post-corona virus disease (COVID) epidemiological investigation. Consequently, a conspicuous void exists, void of the precise data requisite to substantiate the conjecture regarding the surge in post-COVID cardiovascular events and sudden cardiac fatalities as promulgated by media outlets. Nonetheless, the inexorable reality is the discernible surge in sudden cardiac deaths, a trend that was evidently infrequent merely a few years prior. In a meticulous forensic study spearheaded by Sharma et al., encompassing a comprehensive post-mortem assessment of sudden death cases spanning an 18-month period at a tertiary healthcare facility in India, findings unveiled a noteworthy 55% of sudden deaths attributed to cardiac causes, often characterized by significant coronary occlusions. Equally conspicuous were the demographics, with the study depicting a striking male predominance, with an approximate ratio of 11:1, and a median age of 44.5 years [1]. Sun et al. reported a 25% elevation in the incidence of cardiovascular events among young individuals following COVID vaccination within the Israeli population [2].

It is widely acknowledged that nearly 80–90% of sudden cardiac deaths can be traced back to ischemic events precipitated by coronary artery disease [3, 4]. Consequently, it appears judicious to scrutinize the impact of vaccines on the development of coronary artery disease and discern whether any discernible correlation emerges.

COVID-19 vaccines either contain deoxyribonucleic acid (DNA) delivered within non-replicating recombinant adenovirus vector–based systems or messenger RNA (mRNA) technology and lipid nanoparticle delivery systems. All of these vaccines encode the production of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S protein), ultimately triggering an immune response. This immune response, akin to infective endocarditis, can lead to cross-reactivity and foster a vascular immune response and hypercoagulopathy, rapidly obliterating coronary arteries [5]. A systematic review conducted by Fazlollahi et al. which encompassed 69 studies examining cardiac complications following COVID-19 vaccination identified myocarditis as the most prevalent post-vaccination sequel, with patients having a median age of 21 years and 92% of them being male. The majority of these cases (87.7%) manifested after the second dose of mRNA vaccines. Endomyocardial biopsy revealed widespread immune cell infiltration, including a cluster of differentiation 68 (CD68)-positive macrophages and lymphocytes. However, it is important to note that this study predominantly focused on the European population and was predominantly composed of case reports and case series, potentially introducing bias [6]. In a review study by Chen and Su, they concluded that post-vaccination myocardial infarction was more common in older males, with the initial dose of adenoviral vector vaccines seemingly playing a greater role in this complication [7]. In an institutional cohort and systematic review conducted in Singapore by Aye et al., the authors discovered that out of the 77 patients included in their pooled analysis, nearly half exhibited myocarditis, while the other half displayed significant coronary artery disease. Additionally, they proposed that elevated levels of immunoglobulin E (IgE) antibodies could be correlated with an increased risk factor for the development of coronary artery disease following vaccination [8].

In another publication from Italy by Baronti et al., the authors established a temporal association between COVID-19 vaccination and acute myocardial infarction, albeit in a small study population. The authors conducted post-mortem cardiac magnetic resonance imaging (MRI), histopathological, and genetic analyses, along with assessing the presence of anti-platelet factor 4 in a study group of patients who had previously received mRNA-based vaccines. Their findings conclusively established a positive correlation between vaccination and the development of coronary lesions in previously healthy, screened individuals [9].

In a comprehensive review study conducted by Yasmin et al., encompassing 81 articles involving 17,636 individuals who developed post-vaccine morbidity or mortality, a striking 79% of patients presented with thrombosis, while only 2% experienced myocardial infarction, and an additional 2.8% developed myocarditis. It is crucial to note that the follow-up periods in the included studies were relatively short, and the outlook may differ with a more extended mid-term follow-up post-vaccination [10]. A molecular-based study from France by Devaux et al. proposed an alternative mechanism, suggesting that in mRNA-based vaccine recipients already in the process of healing from a low-noise infection, molecular mimicry involving the virus spike protein can disrupt angiotensin-converting enzyme 2 (ACE2) function, leading to acute coronary syndrome in younger individuals [11].

In one of the only comprehensive studies of long-term adverse outcomes following COVID-19 infection (rather than vaccination), researchers Xie et al. drew upon data from the US Department of Veterans Affairs to construct a cohort comprising 153,760 individuals who had experienced COVID-19. Their findings definitively established a significant and substantial increase in the 1-year burden of coronary artery disease among survivors of COVID-19 in the USA. These individuals faced a nearly twofold elevated risk compared to their contemporaries in the same age group. The study attributed this heightened susceptibility to adverse cardiovascular outcomes following COVID-19 infection to a myriad of factors, including complement activation, coagulopathy, and microangiopathy, the downregulation of ACE2, dysregulation of the renin–angiotensin–aldosterone system, autonomic dysfunction, and elevated levels of pro-inflammatory cytokines [12].

Another condition, known as Kounis syndrome or allergic myocardial infarction, represents an acute coronary syndrome characterized by mast cell activation triggered by hypersensitivity, allergy, or anaphylactic reactions, which can occur following vaccination. This syndrome is more commonly associated with ST-elevation myocardial infarction (STEMI) [13]. Currently, Kounis syndrome is under rigorous scrutiny, with a multitude of ongoing research efforts aimed at establishing a definitive link between COVID-19 vaccine–induced acute coronary syndrome and this condition.

In the wake of the ongoing COVID-19 pandemic, the phenomenon of sudden cardiac deaths has garnered widespread attention, fuelled by media reports that have drawn a connection, direct or indirect, to COVID-19 vaccinations. Yet, as we delve into this intricate landscape, it becomes evident that there is a dearth of precise data that unequivocally substantiates this hypothesis. Despite this, a noticeable increase in sudden cardiac deaths has been observed in recent years, raising questions that demand scientific scrutiny. A comprehensive review of available research reveals a complex web of associations and possible mechanisms. COVID-19 vaccines, utilizing diverse technologies such as DNA delivered within non-replicating recombinant adenovirus vectors or mRNA, have one common goal: to stimulate the production of the SARS-CoV-2 spike (S) protein and, consequently, trigger an immune response. This immune response, much like infective endocarditis, has been postulated to potentially lead to cross-reactivity and promote vascular immune responses and hypercoagulopathy, resulting in the rapid occlusion of coronary arteries.

In conclusion, the landscape of COVID-19, vaccination, and cardiovascular implications is multifaceted and evolving. While intriguing associations have emerged, further comprehensive research is imperative to clarify these complex relationships and guide public health policies effectively.

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The authors certify that the research work did not receive any funding from any source.

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Institutional Review Board approval was not necessary because all the data were retrieved from public databases.

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