According to available data, by 30 September 2022, 68% of the world’s population had received at least one dose of the COVID-19 vaccine, and 12.74 billion doses had been administered [1]. The vaccines most commonly administered were Comirnaty (Pfizer/BioNTech), Covishield (Astrazeneca), CoronaVac (Sinovac), Spikevax (Moderna), and Jcovden (Johnson & Johnson) [2]. Of these, approximately 30% of the doses produced by 22 January 2022 were in the form of a novel vaccine with a synthetic N1-methyl-pseudoiridinylated mRNA encapsulated in a lipid nanoparticle (LNP) [3].

LNPs are a new technology that was not used in vaccine delivery until the emergency use authorization (EUA) of the Pfizer/BioNTech BNT162b2 and Moderna mRNA-1273 COVID-19 vaccines [4]. This was also unprecedented in the approval process, being the fastest for any vaccine [5], leaving many concerns with regard to long-term safety [6], which was difficult to evaluate due to the unblinding of the initial clinical trials [7].

Whilst the delivery technology of LNPs have previously been used to deliver small molecules, it has only recently been used to deliver RNA. LNPs are advantageous for targeting brain tissue, as they can cross the blood–brain barrier (BBB) [8,9]. The first drug used and LNP to deliver RNA was a small interfering RNA (siRNA)-based drug, known as Onpattro (Alnylam Pharmaceuticals), first approved in 2018 for the treatment of polyneuropathies [10].

Given both the novelty of the technology and the paucity of data on which approval was based (which was also subject to data integrity issues [11]), long-term effects cannot be definitively ruled out, especially because many of the foundational claims on which approval was based have been contested by recent experiments [12,13,14]. For example, in contrast to claims that the injection stayed at the injection site [15], and that spike protein would only be expressed for a short period of time (based on the lability of non-pseudouridylated RNA [16]), the contents and products of the COVID-19 vaccines have been found in the blood stream of most vaccinees studied within hours to days [12].

The first claim was based on Intramuscular administration [15], and the second claim was based on the lability of RNA [17], with a typical RNA half-life of minutes [18]; however, biodistribution studies have found significant expression of spikes in other tissues and organs [12], and researchers have found both vaccine mRNA and spike protein (which is encoded by the vaccine sequence) two months post-administration [14], and even up to four months post-vaccination [13]. One preprint study of people with SARS-CoV-2 negative post-vaccination Long COVID-19-like symptoms showed spike protein persistence, on average, 105 days post vaccination [19]. Long COVID-19 patients (post SARS-CoV-2 infection) show spike protein persistence up to 15 months [20]. Another study showed spike protein persistence in the gut of long COVID-19 patients, but not in the bloodstream.

Spike proteins can be packaged in exosomes [13], possibly resulting in inflammation and immune activation [21,22] in organs and tissues distant from the injection site [13]. Extracellular vesicles are capable of crossing the blood–brain barrier [23], and LNPs, as well as exosomes, will exchange more readily in small diameter vessels with low flow rates (i.e., capillaries and small vessels) [24]. Importantly, the spike protein seems to additionally impact blood–brain barrier permeability [25,26]. These results challenge the initial mechanistic foundation on which the presumption of safety is contingent.

Compared with other vaccines, COVID-19 vaccines have a much higher adverse event rate [27]. Histopathological findings and autopsies of those dying post-vaccination support the causative role of the vaccine in deaths [28], most commonly from vascular-related events. Pharmacovigilance programs in several countries have observed a safety signal for myocarditis in the COVID-19 vaccinated population [29,30,31]. A US survey found that 19% of myocarditis cases had not recovered at 90 days after onset [32]. In addition, screening of BNT162b2 vaccine recipients among boys aged 13–18 in a Thai study revealed that 2.3% of the boys had at least one elevated cardiac biomarker or positive lab assessment, and 29% had at least one cardiac manifestation, such as tachycardia, palpitation, or myopericarditis [33]. Given this information, and given the ubiquitous use of COVID-19 vaccines, it is possible that widespread subclinical damage exists in the COVID-19 vaccinated population. Structurally, the spike protein, particularly the receptor-binding domain (RBD) of the S1 subunit, has attracted much attention, as it is the most prominent aspect of the viral capsid [34] (It consists of spike (S) and nucleocapsid (N)) glycoproteins. Cell entry is mediated by the binding of Spike RBD to the Angiotensin Converting Enzyme II (ACE2) [35]. Therefore, by preventing this binding through allosteric inhibition, it is possible to prevent the entry of SARS-CoV-2 virions into the cell and subsequent infection [36].

2. Pathophysiology

2.1. Mechanisms of Harm