The Complexities of COVID-19 Vaccines: Exploring Heart Rhythm Disorders and the Molecular Pathway Behind


The global vaccination efforts against SARS-CoV-2 have undoubtedly been monumental in curbing the spread of the virus and mitigating the severity of the disease. Vaccines have played a crucial role in reducing hospitalizations and mortality rates, thereby safeguarding both healthcare systems and economies worldwide [1]. However, alongside the efficacy of vaccines, ensuring their safety remains paramount. As novel vaccines, particularly those based on mRNA technology, were rolled out, concerns arose regarding potential adverse effects, prompting rigorous post-approval monitoring.

In the midst of this landscape, reports emerged indicating a possible link between COVID-19 vaccination, particularly mRNA vaccines, and heart rhythm disorders, alongside other known side effects like myocarditis and pericarditis [3,4]. Despite myocarditis garnering significant attention, heart rhythm disorders have surfaced as an underexplored facet of vaccine-related complications, warranting thorough investigation [3,4]. Notably, unlike myocarditis, heart rhythm disorders haven’t been associated with other vaccines, adding complexity to the understanding of this phenomenon [3,4].

Epidemiological comparisons of heart rhythm disorder incidence pre- and post-vaccination have been hindered by challenges in data availability, compounded by the often asymptomatic nature of such arrhythmias [5,6]. Nonetheless, the significance of these disorders cannot be understated, particularly given the red flags raised in various studies [7,8,9,10,11,12,13].

Analyzing data from vigilance databases and case reports, several studies have shed light on the prevalence and risks associated with post-vaccine arrhythmias [11,13,14]. Findings have highlighted a higher incidence of arrhythmias compared to myocarditis, prompting the need for heightened clinical and scientific attention [11,13,14].

Moreover, investigations into the molecular pathways underlying vaccine-induced arrhythmias have revealed intriguing insights. The interaction between the spike protein, targeted by COVID-19 vaccines, and the ACE2 receptor, pivotal in cardiovascular homeostasis through the renin-angiotensin system (RAS), has been scrutinized [41]. Disruptions in ACE balance, triggered by vaccine-induced spike protein, may lead to inflammatory and thrombotic cascades, culminating in cardiovascular complications, including arrhythmias [41,42,43,44].

Furthermore, distinctions between vaccine platforms, such as mRNA and vector-based vaccines, underscore the complex interplay between innate immune responses and adverse reactions [69,70]. Understanding these nuances is crucial for delineating the unique risks posed by each vaccine type.

Of particular intrigue is the potential role of antibody-mediated immune responses in perpetuating long-term cardiac effects, reminiscent of those observed in viral infections [71,72]. Autoantibodies targeting ACE2, induced by COVID-19 or vaccination, may contribute to cardiac dysregulation, compounding the challenge of deciphering vaccine-related arrhythmias [75,76].

Notably, genetic predispositions and concomitant conditions, such as Brugada syndrome or tubulopathies, further underscore the multifactorial nature of vaccine-related arrhythmias [17,30,80,81]. These insights highlight the intricate interplay between vaccine components, host factors, and immune responses in shaping cardiac outcomes.

In clinical practice, management strategies, such as the use of metoprolol, have shown promise in mitigating vaccine-induced arrhythmias, underscoring the potential therapeutic avenues grounded in understanding the ACE pathway [83,84]. However, comprehensive investigations into the long-term implications and mechanistic underpinnings of vaccine-induced arrhythmias are imperative for informed decision-making and patient care.

The relationship between COVID-19 vaccines and cardiac arrhythmias

The relationship between COVID-19 vaccines, particularly mRNA vaccines, and cardiac arrhythmias has attracted significant attention in the medical community. A detailed exploration of this topic reveals nuanced findings about the risks associated with vaccination, as compared to the risks posed by COVID-19 infection itself.

Studies have identified a higher incidence of arrhythmias following COVID-19 vaccination compared to non-COVID-19 vaccines. A systematic review and meta-analysis, examining data from 36 studies involving over 1.5 billion vaccine doses, reported an incidence of arrhythmias at 291.8 cases per million doses for COVID-19 vaccines, significantly higher than the incidence after non-COVID-19 vaccines, which was reported at 9.9 cases per million doses. The risk of tachyarrhythmia was also notably higher following COVID-19 vaccination, particularly after the third dose. Despite these findings, the overall risk of arrhythmia following COVID-19 vaccination was considered relatively low and should be balanced against the benefits of vaccination and the risks posed by COVID-19 infection itself​​.

Further granularity is provided by a study published in Nature Medicine, which looked at myocarditis, pericarditis, and cardiac arrhythmias following vaccination or SARS-CoV-2 infection. This study highlighted that the increased risk of myocarditis associated with mRNA-based vaccines predominantly affects younger individuals under 40 years. Interestingly, the risk of arrhythmias was not elevated following a first or second dose of either the ChAdOx1 or BNT162b2 vaccine in individuals who had previously tested positive for SARS-CoV-2. The study also categorized cardiac arrhythmias, noting an increased risk for atrial fibrillation or flutter after the first dose of the mRNA-1273 vaccine, and for ventricular fibrillation after the second dose of the ChAdOx1 vaccine​​.

The Centers for Disease Control and Prevention (CDC) conducted an analysis using data from the PCORnet, encompassing the United States from January 2021 to January 2022. This analysis found that cardiac complications were higher following SARS-CoV-2 infection than after mRNA COVID-19 vaccination across all age groups for both males and females. The incidence of myocarditis or pericarditis post-vaccination was within expected ranges and was significantly lower than the incidence following infection. This aligns with findings from other studies indicating a higher risk of myocarditis following SARS-CoV-2 infection as compared to after vaccination​​.

While the data suggests a higher incidence of cardiac arrhythmias following COVID-19 vaccination compared to non-COVID-19 vaccines, the overall risk remains low. Importantly, the risk of cardiac complications, including arrhythmias, is higher following SARS-CoV-2 infection than from the vaccination itself. These findings underscore the need for a nuanced approach to understanding vaccine safety, balancing the risks of vaccination against the clear dangers posed by COVID-19 infection.


The comprehensive study conducted in England aimed to assess the association between COVID-19 vaccination and hospital admissions for cardiac arrhythmias among individuals aged 18 years and over who received at least one dose of the vaccines used for widespread immunization. This analysis, which included a vast dataset of 40 million vaccinated adults with 121 million doses administered, provided significant insights into the safety and effects of COVID-19 vaccines on cardiac health.

The study’s findings indicated an increased risk of admission for arrhythmia events, primarily palpitations or tachycardia, within 14 days following the second priming dose and the first booster dose of the two mRNA vaccines (BNT162b2 and mRNA-1273) in individuals aged 18-49. Specifically, the relative incidence (RI) of admission for these events was notably higher for the mRNA-1273 vaccine compared to the BNT162b2 vaccine, with significant statistical evidence supporting these associations (p < 0.001). However, it’s important to note that these arrhythmia events largely did not include myocarditis, a condition previously associated with mRNA COVID-19 vaccines in some reports.

Contrastingly, no increased risk of other cardiac arrhythmias, including cardiac arrest, was observed within 28 days of vaccination across any dose, age group, or vaccine type. This suggests that the specific findings related to palpitations and tachycardia do not extend to more severe cardiac outcomes. Additionally, the study highlighted that the risk of cardiac arrhythmias of all types, including cardiac arrest, was consistently elevated in individuals testing positive for SARS-CoV-2 infection, emphasizing the significant cardiovascular risks associated with the infection itself.

The analysis employed a self-controlled case series method, modified for fatal events, to estimate the incidence of cardiac events post-vaccination, taking into account various factors such as arrhythmia type, vaccine type, age group, and dose number. This methodological approach allowed for a robust examination of potential vaccine-associated risks while controlling for individual baseline risk factors.

In conclusion, the study provides reassuring evidence regarding the safety of the ChAdOx1 adenovirus vectored vaccine and the mRNA COVID-19 vaccines concerning serious cardiac arrhythmias. It underscores the favorable risk-benefit profile of mRNA booster vaccination, particularly in the context of the ongoing management of the COVID-19 pandemic. The findings contribute valuable information to the ongoing discussions about vaccine safety, offering evidence to guide public health decisions and vaccine recommendations​​​​.

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