Expanded Spectrum and Increased Incidence of Adverse Events Linked to COVID-19 Genetic Vaccines: New Concepts on Prophylactic Immuno-Gene Therapy, Iatrogenic Orphan Disease and Platform-Inherent Challenges

The mRNA- and DNA-based “genetic” COVID-19 vaccines can induce a broad range of adverse events (AEs), with statistics showing significant variation depending on timing and data analysis methods. Focusing only on lipid nanoparticle-enclosed mRNA (mRNA-LNP) vaccines, this review traces the evolution of statistical conclusions on AE prevalence and incidence associated with these vaccines, from initial underestimation of atypical, severe toxicities to recent claims suggesting the possible contribution of Covid-19 vaccinations to the excess deaths observed in many countries over the past few years. Among hundreds of different AEs listed in Pfizer’s pharmacovigilance survey, the present analysis categorizes the main symptoms according to organ systems, nearly all being affected. Using data from the US Vaccine Adverse Event Reporting System and a global vaccination dataset, a comparison of the prevalence and incidence rates of AEs induced by genetic versus flu vaccines revealed an average 26-fold increase in AEs with genetic vaccines. The difference is especially pronounced in the case of severe ‘Brighton-listed’ AEs, which are also observed in COVID-19 and post-COVID conditions. Among these, the increases of incidence rates relative to flu vaccines, given as x-fold rises, were 1,152x, 455x, 226x, 218x, 162x, 152x; and 131x, for myocarditis, thrombosis, death, myocardial infarction, tachycardia, dyspnea, and hypertension, respectively. The review delineates the concepts that genetic vaccines can be regarded as prophylactic immuno-gene therapies, and that the chronic disabling AEs might be categorized as iatrogenic orphan diseases. It also examines the unique vaccine characteristics that could be causally related to abnormal immune responses potentially leading to adverse events and complications. These new insights may contribute to improving the safety of this platform technology and assessing the risk-benefit balance of various products.