The rapid development and deployment of COVID-19 genetic vaccines have raised significant concerns regarding their safety and potential to trigger immune reactions against self-tissues. This paper provides a comprehensive histopathologically supported analysis of how the synthesis of the vaccine-derived spike protein can trigger such reactions beyond the injection site, characterized by robust immune cell recruitment. We examine these immune responses based on histopathological evidence that delineates a pattern consistent with self-directed immune activity, including vaccine-associated myocarditis. In this regard, we report two representative cases, marked by immune-cell infiltration, triggered by the synthesis of the vaccine-derived spike protein in the myocardium and in the liver, respectively. Additionally, we provide a detailed characterization of the process and the immune cells involved in these reactions, based on histopathological findings. Understanding these mechanisms is essential for accurately assessing the potential implications of these vaccination technologies on human health. By emphasizing the need for further research into the pharmacokinetics and off-target effects of COVID-19 genetic vaccines, this paper aims to deepen our understanding of their safety profiles and inform future vaccine development.