Immune Response and Molecular Mechanisms of Cardiovascular Adverse Effects of Spike Proteins from SARS-CoV-2 and mRNA Vaccines

Abstract

The SARS-CoV-2 (severe acute respiratory syndrome coronavirus responsible for the COVID-19 disease) uses the Spike proteins of its envelope for infecting target cells expressing on the membrane the angiotensin converting enzyme 2 (ACE2) enzyme that acts as a receptor. To control the pandemic, genetically engineered vaccines have been designed for inducing neutralizing antibodies against the Spike proteins. These vaccines do not act like traditional protein-based vaccines, as they deliver the message in the form of mRNA or DNA to host cells that then produce and expose the Spike protein on the membrane (from which it can be shed in soluble form) to alert the immune system. Mass vaccination has brought to light various adverse effects associated with these genetically based vaccines, mainly affecting the circulatory and cardiovascular system. ACE2 is present as membrane-bound on several cell types, including the mucosa of the upper respiratory and of the gastrointestinal tracts, the endothelium, the platelets, and in soluble form in the plasma. The ACE2 enzyme converts the vasoconstrictor angiotensin II into peptides with vasodilator properties. Here we review the pathways for immunization and the molecular mechanisms through which the Spike protein, either from SARS-CoV-2 or encoded by the mRNA-based vaccines, interferes with the Renin-Angiotensin-System governed by ACE2, thus altering the homeostasis of the circulation and of the cardiovascular system. Understanding the molecular interactions of the Spike protein with ACE2 and the consequent impact on cardiovascular system homeostasis will direct the diagnosis and therapy of the vaccine-related adverse effects and provide information for development of a personalized vaccination that considers pathophysiological conditions predisposing to such adverse events.

Pyrroloquinoline Quinone (PQQ): a novel approach to managing chronic inflammatory response syndrome and mitochondrial dysfunction

“…Chronic Inflammatory Response Syndrome (CIRS), most commonly associated with mould exposure, shares overlapping features with cytokine storm effects observed in COVID infection and long COVID 39 and mRNA vaccine injury. [40][41][42] With over 13 billion doses of COVID-19 vaccine administered, mRNA vaccines have helped prevent hospitalization and severe disease, but they do not provide sterilizing immunity, resulting in reinfections. In fact, recent research 42 raises serious concerns about the immune tolerance induced by mRNA vaccines and the virus, which could exacerbate the outcome of COVID-19 infections.…”

Desmoglein-2 and COVID-19 complications: insights into its role as a biomarker, pathogenesis and clinical implications

“…The pathogenic mechanism of SARS-CoV-2-related cardiovascular injury has gained significant attention due to its implications for patient outcomes during the COVID-19 pandemic. Two recent studies, one by Xu et al [79] and another by Bellavite et al [80], shed light on different aspects of this complex issue. Xu et al [79] highlightd that COVID-19, primarily considered a respiratory disease, can severely impact various organs, including the heart.…”

“…The interaction of spike proteins with ACE2 receptors can lead to reduced ACE2 activity, contributing to an increased level of angiotensin II, which can adversely affect the inflammation, coagulation and hydroelectrolytic systems. Imbalances in the kinin system, including the 'kinine storm' , have also been implicated in cardiovascular complications [80].…”

“…[79] and another by Bellavite et al . [80], shed light on different aspects of this complex issue. Xu et al .…”

“…On the other hand, Bellavite et al . [80] investigated the cardiovascular effects of genetically engineered vaccines developed to combat the pandemic. These vaccines utilize mRNA or DNA to induce the production of spike proteins, which are part of the SARS-CoV-2 envelope ().…”