The spectrum of side effects of spike-based COVID-19 vaccines is broader and more severe than generally recognised. Adverse cardiovascular events convincingly reflect the mode of action of the spikes, namely the downregulation of the cardiovascular protective angiotensin-converting enzyme 2
(ACE2), which leads to an increase in harmful angiotensin II concentrations and the associated consequences. A fundamental re-evaluation of the benefit-risk assessment of these novel vaccines is mandatory. Healthcare professionals should be educated about the consequences of spike-induced ACE2 downregulation, the resulting symptoms and therapeutic options.

Aims: The aim of this investigation was to determine whether the global and cardiovascular burden associated with spike-based Covid-19 vaccination has continued to increase.

Methods and results: An updated analysis of spontaneously reported individual cases with ADRs and their fatal outcomes associated with Covid-19 vaccines, as well as adverse cardiovascular events caused by the spike-inducing vaccine Tozinameran, was performed.

Data were retrieved from the EudraVigilance web reports of the European Medicines Agency (EMA). All evaluated adverse events correspond to the search terms of the EudraVigilance based on clinical characterisation.

The total number of individual cases (n=2256506; i.e. 2338/day) with adverse effects that were fatal in 2.3% (n=51740; i.e. 54 deaths/day), as well as the wide range of reports of cardiovascular adverse effects, have revealed the unusual magnitude and specificity of these events.

Tachycardia, arrhythmia, atrial fibrillation/flatter, bradyarrhythmia and impaired stimulus formation and conduction (n=57438 combined) dominated the cardiovascular side effect profile of Tozinameran, followed by blood pressure increase (n=25907), myo-/pericarditis (n=23775), heart failure, cardiomyopathy, cardiac flatter/fibrillation, cardiac arrest, circulatory collaps (n=16778 combined) and coronary artery disease/myocardial infarction (n=9912). The importance of acute cardiovascular reactions is underlined by the fact that deaths caused by them accounted for at least one third (35%) of all deaths associated with Tozinameran’s side effects

Based on individual assessment, ARBs are currently recommended in the treatment of spike-induced symptoms.

Conclusions: The spectrum of side effects of spike-based Covid-19 vaccines is more extensive and severe than is generally known, Adverse cardiovascular events convincingly reflect the mode of spike action, namely down-regulating of the cardiovascular protective enzyme ACE2 resulting in increasing Ang II concentrations. A fundamental re-evaluation of the benefit-risk assessment of these novel vaccines is mandatory. Health professionals should be educated about the consequences of spike-induced ACE2 downregulation, the resulting symptoms and therapeutic options.

The protective Angiotensin-Converting Enzyme 2 (ACE2) – essential part of the Renin-Angiotensin-Aldosterone System (RAAS) – is the target receptor for its physiological ligands Angiotensin I and II (Ang I/II) as well as for SARS-CoViruses and – spikes. It mediates Ang II degradation and is the precondition for SARS-CoVirus cell entry, spike-induced adverse reactions, and cytotoxic cell fusion. In spike-induced ACE2 downregulation, Ang II degradation is reduced with the consequence of increasing Ang II concentrations; the counter-regulatory protective Ang 1-7/AT2R/MAS axis is impaired.
The presented analysis provides a substantial body of evidence for the causal involvement of Ang II/activated RAAS in eliciting adverse reactions after application of spike-based vaccine. As an example, some serious organ disturbances or adverse reactions, in which the connection with an activated RAAS is obvious (cardiovascular and blood coagulation disorders, disorders of the nervous and muscular system, inflammatory reactions, auto-immunological, vascular and renal disorders), are presented and discussed.
Only a consistent refraining from any unfavorable influence on the highly complex RAAS enables harm avoidance. To limit or repair harm that has already occurred, RAAS inhibitors or recombinant ACE2 or ACE2 activators are suitable for spike-related symptoms. Based on individual assessment, the preference is currently for ARBs. An individualized approach depending on symptoms, individual conditions and differentiated diagnostics is essential.