Postvaccine “spikeopathy:” what is the long-term neurological risk?

The coronavirus disease 2019 (COVID-19) pandemic prompted the development of a new therapeutic era: that of RNA and DNA vaccines. In contrast to conventional vaccines based on the direct administration of a weakened or inactivated infectious agent, mRNA pseudovaccines provide the human body’s cells with the instructions on how to produce a component against which the immune system needs to defend itself. To make this mode of operation possible, lipid nanoparticles are used to coat the mRNA and transport it into the body’s cells. Once the mRNA is released into the cell, it is translated into a protein (the viral spike protein, in the case of the vaccine against severe acute respiratory syndrome coronavirus 2) by structures called ribosomes. The protein thus produced is intended to trigger an immune response, in which the spike protein is recognized as foreign and is targeted by specific antibodies.

Despite the message of safety and effectiveness that has accompanied the novel COVID-19 vaccines,[1] high incidences of adverse events were soon reported. One of these adverse events, named as post-vaccine “spikeopathy,” was quickly listed by the US Food and Drug Administration and comprised a large number of peripheral, central and autonomous neurological disorders, such as Guillain–Barré syndrome, peripheral facial palsy, acute disseminated encephalomyelitis, transverse myelitis, meningitis, convulsions/seizures, stroke and cerebral venous thrombosis, narcolepsy and cataplexy, and long COVID-19 syndrome.[2] The main mechanism underlying these disorders appears to be deregulation of the renin–angiotensin–aldosterone system (RAAS) via hyperactivity of the angiotensin II type I receptors; the latter is reportedly responsible for prohypertensive, pro-inflammatory, pro-oxidant, prothrombotic, proangiogenic, prohypoxemic, profibrotic, and prohypertrophic effects, among others.[3]

Although the short-term damage to the nervous system induced by postvaccine spikeopathy has been well documented, a worryingly large number of questions concerning the medium and long term remain to be addressed and have obscured the initial general optimism. Indeed, many potentially harmful scientific aspects of this recent technology deserve to be highlighted. They concern (i) the quantity of RNA to be delivered, which varies greatly from one product to another and leads one to suspect that the optimal dose for administration has not been the subject of in-depth research, (ii) the way of controlling the quantity of spike protein produced in the body (which must depend on a multitude of variables, and particularly ones with interindividual differences) and the lifespans of the mRNA and the circulating spike protein (which appears to be degraded less quickly than expected), (iii) the dissemination of the vaccine to parts of the body other than the injection site (the deltoid muscle), which provides a large number of sites (particularly in the brain) for production of the spike protein, and (iv) the putative reverse transcription of mRNA into DNA, which literally means the integration of viral genetic material into the genome of our cells – potentially leading to a “chronic infection,” long-term cellular dysfunction (promoting the development of cancer), and even genetic mutations.

The results of animal studies have recently shown than besides the RAAS deregulation, other pathophysiological mechanisms could also disrupt the nervous system’s normal functioning and thus could contribute to the possible development of serious diseases in the medium or long term. These mechanisms include inhibition of the cholinergic anti-inflammatory pathway (which leads to amyloidogenic inhibition and might contribute to neurodegenerative disorders), elevated expression of alpha-synuclein (an aggregation-prone protein that is additionally implicated in the pathogenesis of Lewy bodies), facilitation of the accumulation of toxic prion-like fibrils in neurons, demyelination (impacting the structure and function of neuronal networks), excess formation of reactive oxygen species (ROS) and thus compromised mitochondrial function, and astrocyte inflammation. Finally, the lipid nanoparticles that coat the spike protein mRNA can cross the blood–brain barrier and potentially have direct neurotoxic effects (such as oxidative stress, apoptosis, inflammation, and probably, genotoxicity through the induction of ROS).[4]

The results of a recent large-scale clinical study appear to confirm the fears raised by the lab work and suggest a potential link between COVID-19 vaccination (particularly mRNA vaccines) and elevated incidences of Alzheimer’s disease and mild cognitive impairment.[5]

This highlights the need for further research to elucidate the relationship between vaccine-induced immune responses and neurodegenerative processes, advocating for continued monitoring and investigation of the long-term neurological impacts of vaccines.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.