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Food and Chemical Toxicology 164 (2022) 113008

Contents lists available at ScienceDirect

Food and Chemical Toxicology
journal homepage: www.elsevier.com/locate/foodchemtox

Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role ofG-quadruplexes, exosomes, and MicroRNAs
Stephanie Seneff a, *, Greg Nigh b, Anthony M. Kyriakopoulos c, Peter A. McCullough daComputer Science and Artificial Intelligence Laboratory, MIT, Cambridge, MA, USA, 02139
Immersion Health, Portland, OR, 97214, USAc
Research and Development, Nasco AD Biotechnology Laboratory, Department of Research and Development, Sachtouri 11, 18536, Piraeus, GreecedTruth for Health Foundation, Tucson, AZ, USAb

A R T I C L E I N F O

A B S T R A C T

Handling Editor: Dr. Jose Luis Domingo

The mRNA SARS-CoV-2 vaccines were brought to market in response to the public health crises of Covid-19. The
utilization of mRNA vaccines in the context of infectious disease has no precedent. The many alterations in thevaccine mRNA hide the mRNA from cellular defenses and promote a longer biological half-life and high pro­duction of spike protein. However, the immune response to the vaccine is very different from that to a SARS-CoV2 infection. In this paper, we present evidence that vaccination induces a profound impairment in type I
interferon signaling, which has diverse adverse consequences to human health. Immune cells that have taken up
the vaccine nanoparticles release into circulation large numbers of exosomes containing spike protein along withcritical microRNAs that induce a signaling response in recipient cells at distant sites. We also identify potential
profound disturbances in regulatory control of protein synthesis and cancer surveillance. These disturbances
potentially have a causal link to neurodegenerative disease, myocarditis, immune thrombocytopenia, Bell’s
palsy, liver disease, impaired adaptive immunity, impaired DNA damage response and tumorigenesis. We show
evidence from the VAERS database supporting our hypothesis. We believe a comprehensive risk/benefit
assessment of the mRNA vaccines questions them as positive contributors to public health.

Keywords:
SARS-CoV-2 mRNA vaccines
Type I interferon Response
Exosomes
G-quadruplexes
microRNAs
Cancer

1. Introduction
Vaccination is an endeavor to utilize non-pathogenic material tomimic the immunological response of a natural infection, thereby
conferring immunity in the event of pathogen exposure. This goal has
been primarily pursued through the use of both whole organism andattenuated virus vaccines. Use of fragments of virus or their protein
products, referred to as “subunit vaccines,” has been more technicallychallenging (Bhurani et al., 2018). In any event, an implicit assumption
behind the deployment of any vaccination campaign is that the vaccine
confers the effects of a ‘benign infection,’ activating the immune systemagainst future exposure, while avoiding the health impacts of actual
infection.
Much of the literature on this related to COVID-19 suggests that theimmune response to mRNA-based vaccination is similar to naturalinfection. A preprint study found “high immunogenicity of BNT162b2
vaccine in comparison with natural infection.” The authors found there

to be many qualitative similarities though quantitative differences(Psichogiou et al., 2021a). Jhaveri (2021) suggests that mRNA vaccines
do what infection with the virus does: “The protein is produced andpresented in the same way as natural infection.” The U.S. Centers for
Disease Control and Prevention (CDC) makes the case based upon
antibody titers generated by prior infection vs. vaccination, in addition
to production of memory B cells, to argue that the immune response tovaccination is analogous to the response to natural infection (Centers for
Disease Control and Prevention, 2021a). It is this similarity in the hu­
moral immune response to vaccination vs natural infection, paired withboth trial and observational data demonstrating reduced risk of infec­
tion following vaccination, that stands as the justification for the massvaccination campaign.
Our paper summarizes the current literature on mRNA and its effects
on the molecular biology within human cells. We recognize that there isa wide range of opinions in this nascent phase of mRNA technology.
Given its widespread deployment ahead of basic work on so many of the* Corresponding author.
E-mail addresses: seneff@csail.mit.edu (S. Seneff), drnigh@immersionhealthpdx.com (G. Nigh), antkyriak@gmail.com (A.M. Kyriakopoulos), peteramccullough@gmail.com (P.A. McCullough).
https://doi.org/10.1016/j.fct.2022.113008
Received 9 February 2022; Received in revised form 3 April 2022; Accepted 8 April 2022
Available online 15 April 2022
0278-6915/© 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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Food and Chemical Toxicology 164 (2022) 113008

mechanisms we discuss here, we believe that our work is important forproviding a broad understanding of present and future reviews that
relate to the burgeoning preclinical molecular work being done in thisarea.
In this paper, we explore the scientific literature suggesting thatvaccination with an mRNA vaccine initiates a set of biological events
that are not only different from that induced by infection but are inseveral ways demonstrably counterproductive to both short- and longterm immune competence and normal cellular function. These vacci­
nations have now been shown to downregulate critical pathways related
to cancer surveillance, infection control, and cellular homeostasis. They
introduce into the body highly modified genetic material. A preprint hasrevealed a remarkable difference between the characteristics of theimmune response to an infection with SARS-CoV-2 as compared with the
immune response to an mRNA vaccine against COVID-19 (Ivanova et al.,2021). Differential gene expression analysis of peripheral dendritic cells
revealed a dramatic upregulation of both type I and type II interferons(IFNs) in COVID-19 patients, but not in vaccinees. One remarkable
observation they made was that there was an expansion of circulatinghematopoietic stem and progenitor cells (HSPCs) in COVID-19 patients,
but this expansion was notably absent following vaccination. A striking
expansion in circulating plasmablasts observed in COVID-19 patientswas also not seen in the vaccinees. All of these observations are
consistent with the idea that the anti-COVID-19 vaccines actively sup­press type I IFN signaling, as we will discuss below. In this paper we will
be focusing extensively, though not exclusively, on vaccination-induced
type I IFN suppression and the myriad downstream effects this has on therelated signaling cascade.
Since long-term pre-clinical and Phase I safety trials were combinedwith Phase II trials, then phase II and III trials were combined (Kwok,
2021); and since even those were terminated early and placebo arms
given the injections, we look to the pharmacosurveillance system andpublished reports for safety signals. In doing so, we find that that evi­
dence is not encouraging. The biological response to mRNA vaccination
as it is currently employed is demonstrably not similar to naturalinfection. In this paper we will illustrate those differences, and we will
describe the immunological and pathological processes we expect are
being initiated by mRNA vaccination. We will connect these underlying
physiological effects with both realized and yet-to-be-observed mor­bidities. We anticipate that implementation of booster vaccinations on awide scale will amplify all of these problems.
The mRNA vaccines manufactured by Pfizer/BioNTech and Moderna
have been viewed as an essential aspect of our efforts to control the
spread of COVID-19. Countries around the globe have been aggressively
promoting massive vaccination programs with the hope that such efforts
might finally curtail the ongoing pandemic and restore normalcy. Gov­
ernments are reticent to consider the possibility that these injections
might cause harm in unexpected ways, and especially that such harmmight even surpass the benefits achieved in protection from severe
disease. It is now clear that the antibodies induced by the vaccines fadein as little as 3–10 weeks after the second dose (Shrotri et al., 2021), suchthat people are being advised to seek booster shots at regular intervals(Centers for Disease Control and Prevention, 2021b). It has also become
apparent that rapidly emerging variants such as the Delta and now the
Omicron strain are showing resistance to the antibodies induced by thevaccines, through mutations in the spike protein (Yahi et al., 2021).
Furthermore, it has become clear that the vaccines do not prevent
transmission of the disease, but can only be claimed to reduce symptom
severity (Kampf, 2021a). A study comparing vaccination rates with
COVID-19 infection rates across 68 countries and 2947 counties in the
United States in early September 2021, found no correlation between
the two, suggesting that these vaccines do not protect from spread of thedisease (Subramanian and Kumar, 2947). Regarding symptom severity,even this aspect is beginning to be in doubt, as demonstrated by anoutbreak in an Israeli hospital that led to the death of five fully vacci­
nated hospital patients (Shitrit et al., 2021). Similarly, Brosh-Nissimov

et al. (2021) reported that 34/152 (22%) of fully vaccinated patientsamong 17 Israeli hospitals died of COVID-19.
The increasing evidence that the vaccines do little to control disease
spread and that their effectiveness wanes over time make it even moreimperative to assess the degree to which the vaccines might cause harm.
That SARS-CoV-2 modified spike protein mRNA vaccinations have bio­
logical impacts is without question. Here we attempt to distinguish those
impacts from natural infection, and establish a mechanistic frameworklinking those unique biological impacts to pathologies now associatedwith vaccination. We recognize that the causal links between biologicaleffects initiated by mRNA vaccination and adverse outcomes have notbeen established in the large majority of cases.
2. Interferons: an overview with attention to cancer
surveillance
Discovered in 1957, interferon (IFN) earned its name with therecognition that cells challenged by attenuated influenza A virus createda substance that “interfered with” a subsequent infection by a live virus(Lindenmann, 1982). IFN is now understood to represent a very large
family of immune-modulating proteins, divided into three types,
designated as type I, II, and III based upon the receptors each IFN in­teracts with. Type I IFN includes both IFN-α and IFN-β, and this type isthe most diverse, being further divided into seventeen subtypes. IFN-α
alone has thirteen subtypes currently identified, and each of those isfurther divided into multiple categories (Wang et al., 2017a). Type I
IFNs play a powerful role in the immune response to multiple stressors.
In fact, they have enjoyed clinical therapeutic value as a treatment op­
tion for a variety of diseases and conditions, including viral infections,solid tumors, myeloproliferative disorders, hematopoietic neoplasms
and autoimmune diseases such as multiple sclerosis (Passegu and Ernst,
2009).
As a group, IFNs play exceedingly complicated and pleiotropic roles
that are coordinated and regulated through the activity of the family of
IFN regulatory factors, or IRFs (Kaur and Fang, 2020). IRF9 is mostdirectly involved in anti-viral as well as anti-tumor immunity and ge­
netic regulation (Alsamman and El-Masry, 2018; Huang et al., 2019;
Zitvogel et al., 2015).
Closely related to this are plasmacytoid dendritic cells (pDCs), a raretype of immune cell that circulate in the blood but migrate to peripheral
lymphoid organs during a viral infection. They respond to a viral
infection by sharply upregulating production of type I IFNs. The IFN-α
released in the lymph nodes induces B cells to differentiate into plas­mablasts. Subsequently, interleukin-6 (Il-6) induces plasmablasts to
evolve into antibody-secreting plasma cells (Jego et al., 2003). Thus,
IFNs play a critical role in both controlling viral proliferation andinducing antibody production. Central to both antiviral and anticancer
immunity, IFN-α is produced by macrophages and lymphocytes wheneither is challenged with viral or bacterial infection or encounters tumor
cells (De Andrea et al., 2002). Its role as a potent antiviral therapy has
been recognized in the treatment of hepatitis C virus complications(Feng et al., 2012), Cytomegalovirus infection (Delannoy et al., 1999),
chronic active ebola virus infection (Sakai et al., 1998), inflammatory
bowel disease associated with herpes virus infection (Ruther et al.,1998), and others.
Impaired type I IFN signaling is linked to many disease risks, mostnotably cancer, as type I IFN signaling suppresses proliferation of bothviruses and cancer cells by arresting the cell cycle, in part throughupregulation of p53, a tumor suppressor gene, and various cyclindependent kinase inhibitors (Musella et al., 2017; Matsuoka et al.,1998). IFN-α also induces major histocompatibility (MHC) class 1 anti­
gen presentation by tumor cells, causing them to be more readily
recognized by the cancer surveillance system (Heise et al., 2016;
Sundstedt et al., 2008). The range of anticancer effects initiated by IFN-α
expression is astounding and occurs through both direct and indirect
mechanisms. Direct effects include cell cycle arrest, induction of cell2

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Food and Chemical Toxicology 164 (2022) 113008

differentiation, initiation of apoptosis, activation of natural killer andCD8+ T cells, and others (Schneider et al., 2014).
The indirect anticancer effects are predominantly carried out
through gene transcription activation of the Janus kinase signal trans­
ducer and activator of transcription (JAK/STAT) pathway. IFN-α bind­ing on the cell surface initiates JAK, a tyrosine kinase, to phosphorylate
STAT1 and STAT2 (Asmana Ningrum, 2014). Once phosphorylated,these STATs form a complex with IRF9, one of a family of IRFs that playa wide range of roles in oncogene regulation and other cell functions(Takaoka et al., 2008). It is this complex, named IFN-stimulated gene
factor 3 (ISGF3), that translocates to the cell nucleus to enhance theexpression of at least 150 genes (Schneider et al., 2014). IRF9 has beensuggested to be the primary member of the IRF family of proteins
responsible for activation of the IFN-α antiproliferative effects, and thatappears to be through its binding to the tumor necrosis factor-related
apoptosis-inducing ligand (TRAIL) receptor 1 and 2 (TRAIL-R1/2)(Tsuno et al., 2009). IRF7 is another crucial member of the IRF family ofproteins involved early in the response to a viral infection. It is normally
expressed in low amounts but is strongly induced by ISGF3. IRF7 also
undergoes serine phosphorylation and nuclear translocation to further
activate the immune response. IRF7 has a very short half-life, so its
gene-induction process is transient, perhaps to avoid overexpression of
IFNs (Honda et al., 2006).
Once TRAIL is bound by IRF9, it is then able to act as a ligand for
Death Receptor 4 (DR4) or DR5, initiating a cascade of events involving
production of caspase 8 and caspase 3, and ultimately triggering
apoptosis (Sayers, 2011). Dysregulation of this pathway, through sup­pression of either IFN-α or IRF9 and the resulting failure to bind
TRAIL-R, has been associated with several hematologic malignancies(Testa, 2010) and has been shown to increase the metastatic potential inanimal models of melanoma, colorectal cancer, and lymphoma (Finn­berg and El-Deiry, 2008).
IFN-α both initiates and orchestrates a wide range of cancer sup­pressing roles. Dunn et al. (2005) showed that IFN-α plays an active rolein cancer immunoediting, its locus of action being hematopoietic cells
that are “programmed” via IFN-α binding for tumor surveillance. It is via
the exceedingly complex interactions between type I IFNs and IRF7 andIRF9 in particular that a great deal of antiproliferative effects are carriedout. This is evidenced by the large number of studies showing increased
tumor growth and/or metastases associated with a wide number ofcancer types.
For example, Bidwell et al. (2012) found that, among over 800 breast
cancer patients, those with high expression of IRF7-regulated genes had
significantly fewer bone metastases, and they propose assessment ofthese IRF7-related gene signatures as a way to predict those at greatest
risk. Use of microRNA to target IRF7 expression has also been shown toenhance breast cancer cell proliferation and invasion in vitro (Li et al.,2015). Zhao et al. (2017) found a similar role for IRF7 in relation to bonemetastases in a mouse model of prostate cancer. Regarding theanti-cancer mechanism behind IRF7 expression, Solis et al. (2006) foundthat IRF7 induces transcription of multiple genes and translation of theirdownstream protein products including TRAIL, IL-15, ISG-56 and CD80,
with the noted therapeutic implications.
IRF9, too, has a central role to play in cancer surveillance and pre­vention. Erb et al. (2013) demonstrated that IRF9 is the mediatorthrough which IL-6 augments the anti-proliferation effects of IFN-α
against prostate cancer cells. Tian et al. (2018) found IRF9 to be a key
negative regulator of acute myeloid leukaemia cell proliferation andevasion of apoptosis. It does so, at least in part, through acetylation of
the master regulatory protein p53.
Both IFN-α and IRF9 are also apparently necessary for the cancerpreventative properties of a fully functional BRCA2 gene. In a study
presented as an abstract at the First AACR International Conference on
Frontiers in Basic Cancer Research, Mittal and Chaudhuri (2009)
describe a set of experiments which show for the first time that BRCA2
expression leads to increased IFN-α production and augments the signaltransduction pathway resulting in the complexing of IRF9, STAT1 and
STAT2 described previously. Two years prior, Buckley et al. (2007) had
established that BRCA1 in combination with IFN-γ promotes type I IFNs
and subsequent production of IRF7, STAT1, and STAT2. Thus, theexceedingly important cancer regulatory genes BRCA1 and BRCA2 relyon IRF7 and IRF9, respectively, to carry out their protective effects.
Rasmussen et al. (2021) reviewed compelling evidence that deficiencies
of either IRF7 or IRF9 lead to significantly greater risk of severe
COVID-19 illness. Importantly, they also note that evidence suggests
type I IFNs play a singularly important role in protective immunity
against COVID-19 illness, a role that is shared by multiple cytokines inmost other viral illnesses including influenza.
As will be discussed in more detail below, the SARS-CoV-2 spikeglycoprotein modifies host cell exosome production. Transfection ofcells with the spike protein’s gene and subsequent SARS-CoV-2 spike
protein production results in those cells generating exosomes containing
microRNAs that suppress IRF9 production while activating a range ofpro-inflammatory gene transcripts (Mishra and Banerjea, 2021). Since
these vaccines are specifically designed to induce high and ongoingproduction of SARS-CoV-2 spike glycoproteins, the implications areominous. As described above, inhibition of IRF9 will suppress TRAIL andall its regulatory and downstream apoptosis-inducing effects. IRF9
suppression via exosomal microRNA should also be expected to impair
the cancer-protective effects of BRCA2 gene activity, which depends onthat molecule for its activity as described above. BRCA2-associatedcancers include breast, fallopian tube, and ovarian cancer for women,
prostate and breast cancer for men, acute myeloid leukaemia in chil­dren, and others (National Cancer Institute, 2021).
Vaccination has also been demonstrated to suppress both IRF7 and
STAT2 (Liu et al., 2021). This can be expected to interfere with thecancer-protective effects of BRCA1 as described above. Cancers associ­ated with impaired BRCA1 activity include breast, uterine, and ovariancancer in women; prostate and breast cancer in men; and a modest in­crease in pancreatic cancer for both men and women (Cancer risk andBRCA1 gene, 2021).
Reduced BRCA1 expression is linked to both cancer and neuro­
degeneration. BRCA1 is a well-known breast cancer susceptibility gene.
BRCA1 inhibits breast cancer cell proliferation through activation of
SIRT1 and subsequent suppression of the androgen receptor (Zhang
et al., 2016). In a study conducted by Suberbielle et al. (2015), reduced
levels of BRCA1 were found in the brains of Alzheimer’s patients.
Furthermore, experiments with knocking down neuronal BRCA1 in thedentate gyrus of mice showed that DNA double-strand breaks wereincreased, along with neuronal shrinkage and impairments in synaptic
plasticity, learning and memory.
Analysis detailed in a recent case study on a patient diagnosed with arare form of lymphoma called angioimmunoblastic T cell lymphoma
provided strong evidence for unexpected rapid progression of lympho­
matous lesions after administration of the BNT162b2 mRNA booster
shot (Goldman et al., 2021). Comparisons of detailed metrics for hy­
permetabolic lesions conducted immediately before and 21 days after
the vaccine booster revealed a five-fold increase after the vaccine, withthe post-booster test revealing a 2-fold higher activity level in the rightarmpit compared to the left one. The vaccine had been injected on theright side. It is worth pointing out in this regard that lymphoid malig­nancies have been associated with suppression of TRAIL-R1 (MacFar­
lane et al., 2005).
Given the universally recognized importance of optimally func­
tioning BRCA1/2 for cancer prevention and given the central role of the
TRAIL signal transduction pathway for additional cancer surveillance,
the suppression of IRF7 and IRF9 through vaccination and subsequent
SARS-CoV-2 spike glycoprotein production is extremely concerning forlong-term cancer control in SARS-CoV-2 mRNA genetic vaccine injected
populations.

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3. Considerations in the design of mRNA vaccines

markers to assess the early activation of innate immune mechanisms andthe underlying reactogenicity under the BIOVACSAFE consortium pro­
tocols (Forni and Mantovani, 2021; Weiner et al., 2019). However, tothe best of our knowledge these safety protocols have not been includedin the assessment of induced innate immunity by the SARS-CoV-2 mRNA
genetic vaccines (Mulligan et al., 2020).
In this regard, in the case of SARS-CoV-2 BNT162b2 mRNA vaccine,unlike the immune response induced by natural SARS-CoV-2 infection,
where a robust interferon response is observed, those vaccinated with
BNT162b2 mRNA vaccines developed a robust adaptive immune
response which was restricted only to memory cells, i.e., an alternativeroute of immune response that bypassed the IFN mediated pathways(Mulligan et al., 2020). Furthermore, due to subsequent mutations in the
SARS-CoV-2 spike protein, there is a substantial loss of neutralizing
antibodies induced by the BNT162b2 mRNA vaccine compared to those
conferred by the SARS-CoV-2 mutants alone (Collier et al., 2021). In that
respect, as vaccine developers admit: “Vaccine RNA can be modified byincorporating 1-methylpseudouridine, which dampens innate immune
sensing and increases mRNA translation in vivo.” (Mulligan et al., 2020;
Katalin Karikó et al., 2008). Bearing in mind the multiple mutations that
SARS-CoV-2 develops, as for example in the Brazil outbreaks (Timmers
et al., 2021), an effective immune response that prevents the spread of
SARS-CoV2 mutants necessarily involves the development of a robust
IFN-I response as a part of the innate immune system. This response also
requires the involvement of a functional NF-κB response. Unfortunately,
spike glycoprotein overexpression dismantles the NF-κB pathway re­sponses, and this molecular event can be augmented by
spike-protein-coding mRNAs (Kyriakopoulos and McCullough, 2021;
Jiang and Mei, 2021).
For successful mRNA vaccine design, the mRNA needs to be encap­
sulated in carefully constructed particles that can protect the RNA fromdegradation by RNA depolymerases. The mRNA vaccines are formulated
as lipid nanoparticles containing cholesterol and phospholipids, with themodified mRNA complexed with a highly modified polyethylene glycol(PEG) lipid backbone to promote its early release from the endosome
and to further protect it from degradation (Hou et al., 2021). The hostcell’s existing biological machinery is co-opted to facilitate the natural
production of protein from the mRNA through endosomal uptake of alipid particle (Hou et al., 2021). A synthetic cationic lipid is added aswell, since it has been shown experimentally to work as an adjuvant todraw immune cells to the injection site and to facilitate endosomal
escape. de Beuckelaer et al. (2016) observed that “condensing mRNA
into cationic lipoplexes increases the potency of the mRNA vaccine
evoked T cell response by several orders of magnitude.” Anotherimportant modification is that they replaced the code for two adjacentamino acids in the genome with codes for proline, which causes the
spike glycoprotein to stay in a prefusion stabilized form (Wrapp et al.,2020).
The SARS-CoV-2 spike glycoprotein mRNA is further “humanized”
with the addition of a guanine-methylated cap, 3′ and 5′ untranslated
regions (UTRs) copied from those of human proteins, and finally a longpoly(A) tail to further stabilize the RNA (Kyriakopoulos and McCul­lough, 2021). In particular, researchers have cleverly selected the 3′ UTR
taken from globins which are produced in large quantities by erythro­cytes, because it is very effective at protecting the mRNA from degra­
dation and maintaining sustained protein production (Orlandini vonNiessen et al., 2019). This is to be expected, since erythrocytes have nonucleus, so they are unable to replace the mRNAs once they aredestroyed. Both the Moderna and the Pfizer vaccines adopted a 3′ UTR
from globins, and the Pfizer vaccine also uses a slightly modified globin
5′ UTR (Xia, 2021). de Beuckelaer et al. (2016) aptly summed up theconsequences of such modifications as follows: “Over the past years,
technical improvements in the way IVT [in vitro transcribed] mRNAs areprepared (5′ Cap modifications, optimized GC content, improved polyA
tails, stabilizing UTRs) have increased the stability of IVT mRNAs tosuch extent protein expression can now be achieved for days after direct

Over the last three decades, the mRNA technological platform aimed
to develop effective and safe nucleic acid therapeutic tools is said to haveovercome serious obstacles on the coded product instability, the over­whelming innate immunogenicity, and on the delivery methodologies(Pardi et al., 2018). One of the major success stories of mRNA use as a
genetic vaccination tool is on the introduction of robust immunity
against cancer (Van Lint et al., 2015). In addition, the potential ofmRNAs to restore or replace various types of proteins in cases of rare
genetic metabolic disorders like Fabry disease has offered great potential
therapeutic alternatives where no other medication has proved to be
successful (Martini and Guey, 2019). However, in the case of mRNA use
as genetic vaccines against infectious diseases, the preliminary safety
investigations seemed to be premature for a world-wide use in thegeneral population (Pardi et al., 2018; Doulberis et al., 2021).
Although there are essential epitopes on other SARS-CoV-2 proteins
where an antibody response could have provided essential immunoge­
nicity, well known from SARS-CoV-1 (Gordon et al., 2020), the primary
goal of the developers of the SARS-CoV-2 mRNA vaccines was to design
a vaccine that could induce a robust antibody response exclusively to the
spike glycoprotein. Such antibodies, especially IgA in the nasopharynx,
should cause the invading viruses to be quickly cleared before they could
invade host cells, thus arresting the disease process early on. As statedsuccinctly by Kaczmarek et al. (2021):“The rationale behind vaccination is to provide every vaccinatedperson with protection against the SARS-CoV-2 virus. This protection isachieved by stimulating the immune system to produce antibodies
against the virus and to develop lymphocytes that will retain memory
and the ability to fight off the virus for a long time.” However, since
vaccination is given parenterally, IgG is the principal antibody class thatis raised against the SARS-CoV-2 spike glycoprotein, not IgA (Wisnewski
et al., 2021).
Vaccines generally depend upon adjuvants such as aluminum andsqualene to provoke immune cells to migrate to the injection site
immediately after vaccination. In the history of mRNA vaccine devel­
opment, it was initially hoped that the mRNA itself could serve as its
own adjuvant. This is because human cells recognize viral RNA as
foreign, and this leads to upregulation of type I IFNs, mediated via toll
like receptors such as TLR3, TLR7 and TLR8 (Karik ó et al., 2005).
However, with time it became clear that there were problems withthis approach, both because the intense reaction could cause flu-like
symptoms and because IFN-α could launch a cascade response thatwould lead to the breakdown of the mRNA before it could produce
adequate amounts of SARS-CoV-2 spike glycoprotein to induce an im­
mune response (de Beuckelaer et al., 2016). A breakthrough came when
it was discovered experimentally that the mRNA coding for the spike
protein could be modified in specific ways that would essentially fool thehuman cells into recognizing it as harmless human RNA. A seminal
paper by Karikó et al. (2005) demonstrated through a series of in vitro
experiments that a simple modification to the mRNA such that all uri­dines were replaced with pseudouridine could dramatically reduce
innate immune activation against exogenous mRNA. Andries et al.
(2015) later discovered that 1-methylpseudouridine as a replacement
for uridine was even more effective than pseudouridine and could
essentially abolish the TLR response to the mRNA, preventing the acti­
vation of blood-derived dendritic cells. This modification is applied inboth the mRNA vaccines on the market (Park et al., 2021).
Rather prophetically, the extensive review by Forni and Mantovani(2021) has raised serious questions about the development of innate
immunity by the mRNA SARS-CoV-2 genetic vaccinations. As the au­thors declared: “Due to the short development time and the novelty ofthe technologies adopted, these vaccines will be deployed with several
unresolved issues that only the passage of time will permit to clarify.”
Subsequently, the authors recommended including certain molecules
such as the long pentraxin PTX3 as representative humoral immunity
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in vivo administration of the mRNA.”
However, the optimized analogue cap formation of synthetic mRNAs
inevitably forces the recipient cells to undergo a cap-dependent pro­longed translation, ignoring homeostatic demands of cellular physiology(Kyriakopoulos and McCullough, 2021). The cap 2’-O methylation car­ried out by cap 2′ -O methyltransferase (CMTR1) serves as a motif thatmarks the mRNA as “self,” to prevent recognition by IFN-induced RNA
binding proteins (Williams et al., 2020). Thus, the mRNA in the vac­cines, equipped with the cap 2’-O methylation motif, evades detection as
a viral invasion. Furthermore, the overwhelming impetus for cells toperform a single and artificial approach to translation according to therobust capping and synthetic methylations of mRNAs in vaccines isfundamentally associated with disease progression due to differential
rather than normal signaling of pattern recognition receptors (PRRs)(Leung and Amarasinghe, 2016).
The regulatory process controlling mRNA translation is extremelycomplex, and it is highly disturbed in the context of mRNA vaccines(Kyriakopoulos and McCullough, 2021; Leung and Amarasinghe, 2016).
Briefly, the idea is for mRNA vaccines to achieve the intended goal (i.e.,
production of the modified spike protein) through a stealth strategy thatbypasses the natural immunological response to RNA-type viral infec­
tion. Injected lipid nanoparticles containing mRNA are brought to thecell interior via endocytosis. The mRNA escapes its lipid carrier andmigrates to the ribosome, where it is abundantly translated into its final
protein product, following an optimized program for producing large
quantities of a specific protein over an extended period of time. These
modified SARS-CoV-2 spike glycoproteins then follow one of three pri­mary pathways. Some are proteolytically degraded and fragments arebound by MHC class I molecules for surface presentation to cytotoxic
T-cells. A second pathway has those same spike glycoprotein fragments
bind MHC class II molecules, move to the cell surface, and activate
T-helper cells. A final pathway has soluble spike glycoproteins extruded
from the cell in exosomes, where they can be recognized by B-cell-ac­
tivated spike-glycoprotein-specific antibodies (Chaudhary et al., 2021).
A recent early-release study has found that the mRNA in the COVID19 vaccines is present in germinal centers in secondary lymphoid tissue
long after the vaccine is administered, and that it continues to synthesize
spike glycoprotein up to at least sixty days post-vaccination (Röltgen
et al., 2022). This suggests that immune cells taking up the mRNA in thearm muscle migrate into the lymph system to the lymph nodes, pre­sumably in order to expose B-cells and T-cells to the toxic antigen. The
persistence of the mRNA in the lymph nodes and its sustained synthesisof SARS-CoV-2 spike glycoprotein reflect the clever engineering
involved in the mRNA technology, as described above.
In the end, it is through utilization of nanolipids and sophisticatedmRNA technology that the normal immune response to exogenous RNA
is evaded in order to produce a strong antibody response against an
exogenous RNA virus.

The altered codon assignments within the mRNA template dramaticallyincrease the quantity of polypeptides and/or proteins produced (Mauro
and Chappell, 2014). Synonymous codon replacement also results in achange in the multifunctional regulatory and structural roles of resulting
proteins (Shabalina et al., 2013). For this reason, codon optimization has
been cautioned against due to its consequent changes causing pertur­
bation in the secondary conformation of protein products with poten­
tially devastating effects on their resulting immunogenicity, efficacy andfunction (Zhou et al., 2013; Agashe et al., 2013). Notably, various
human diseases are the result of synonymous nucleotide polymorphisms(McCarthy et al., 2017).
In an experiment where GC-rich and GC-poor versions of mRNAtranscripts for heat shock protein 70 were configured in the context ofidentical promoters and UTR sequences, it was found that GC-rich genes
were expressed several-fold to over a hundred-fold more efficiently thantheir GC-poor counterparts (Kudla et al., 2006). This is partly because allof the preferred mammalian codons have G or C nucleotides in the third
position. It is also well documented that AU-rich elements in the 3’ UTRs
can destabilize mRNA (Otsuka et al., 2019). What may be of particularconcern is the fact that GC enrichment content in vaccine mRNAs results
in an enhanced ability for potential G-quadruplex (pG4) formations inthese structures, and this could cause onset of neurological disease(Wang et al., 2021). Remarkably, the human prion protein (PrP) genetic
sequence contains multiple G4 forming motifs, and their presence may
form the missing link in the initial conversion of PrP to the misfolded
form, PrPsc (Olsthoorn, 2014). PrP binding to its own mRNA may be theseed that causes the protein to misfold. This observation is particularly
concerning in light of the fact that the SARS-CoV-2 spike glycoprotein
has prion-like characteristics (Tetz and Tetz, 2022).
On the one hand, the GC content has a key role in the modulation oftranslation efficiency and control of mRNA expression in mammals(Babendure et al., 2006). Especially during translation initiation, the GC
content operating as a cis-acting mRNA element orchestrates the 43S
ribosomal pre-initiation complex attachment and thereafter the assem­
bly of the eukaryotic translation initiation factor 4F (eIF4F) complex.
One representative example of this system in action is the regulation of αand β globin mRNA expression through their 5′ untranslated regions(5′ UTRs) (Babendure et al., 2006).
On the other hand, the presence of pG4s in RNAs is implicated incancer biology as key determinants of the regulation of G4 RNA binding
proteins such as helicase (Herdy et al., 2018). Generally, the G-quad­ruplexes in RNAs have essential roles in a) the regulation of gene
expression, b) the localization of ribonuclear proteins, c) the mRNA
localization and d) the regulation of proto-oncogene expression (Fayet al., 2017).
Regarding SARS-CoV-2, relevant studies reveal overwhelming simi­
larities between SARS-CoV-2 pG4s, including in RNA coding for SARSCoV-2 spike glycoprotein, and those sequenced in the human tran­
scriptome (Zhang et al., 2020). Thus, it can be inferred that synthetic
mRNAs in vaccines carrying more pG4 structures in their coding
sequence for SARS-CoV-2 spike glycoprotein will amplify and compound
the potential post-transcriptional disorganization due to G4-enriched
RNA during natural SARS-CoV-2 infection. Moreover, the cellular
nucleic acid binding protein (CNBP), which is the main cellular proteinthat binds to the SARS-CoV-2 RNA genome in human-infected cells(Schmidt et al., 2021), binds to and promotes the unfolding of
SARS-CoV-2 G4s formed by both positive and negative sense template
strands of the SARS-CoV-2 RNA genome. A similar modulation of CNBP
on vaccine mRNA G4s and promotion of G4 equilibrium towards
unfolded conformations create favorable conditions for miRNA binding,and this will have a direct impact on miRNA-dependent regulation ofgene expression (Rouleau et al., 2017).
The negative-sense RNAs are intermediate molecules produced by
the replicase transcriptase complex (RTC) formed by the nonstructuralproteins of coronaviruses (including SARS-CoV-2) to provide efficiency
in replication and transcription (Bezzi et al., 2021; Sola et al., 2015).

4. GC enrichment and potential G4 (pG4) structures in vaccine
mRNAs
Recently, members of our team investigated possible alterations insecondary structure of mRNAs in SARS-CoV-2 vaccines due to codon
optimization of synthetic mRNA transcripts (McKernan et al., 2021).
This study has shown that there is a significant enrichment of GC content
in mRNAs in vaccines (53% in BNT162b2 and 61% in ModernamRNA-1273) as compared to the native SARS-CoV-2 mRNA (36%). The
enriched GC content of mRNAs is the result of codon optimization per­formed during the development of the mRNAs used in SARS-CoV-2
vaccines, apparently without determining the effect on secondary
structures, particularly the Guanine quadruplex (G quadruplex) forma­tion (McKernan et al., 2021).
Codon optimization describes the production of synthetic, codonoptimized polypeptides and proteins used in biotechnology therapeu­
tics (such as the synthetic mRNAs used for SARS-CoV-2 vaccination).
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This, however, introduces another potentially serious complication
associated with vaccination. Co-infection with other negative sense RNA
viruses such as hepatitis C (Jaubert et al., 2018) or infection by othercoronaviruses contemporaneous with vaccination periods would pro­vide the necessary machinery of RTC to reproduce negative sense in­termediates from synthetic mRNAs and therefore amplify the presenceof pG4s by negative sense templates. This would result in further epi­
transcriptomic dysregulation (Spiegel et al., 2020).
Summarizing the topic to this point, the enrichment of GC content invaccine mRNA will inevitably lead to an increase in the pG4 content of
the vaccines. This, in turn, will lead to dysregulation of the G4-RNAprotein binding system and a wide range of potential diseaseassociated cellular pathologies including suppression of innate immu­
nity, neurodegeneration, and malignant transformation (Herdy et al.,2018).
Concerning the post translational dysregulation due to emergence of
new G4 structures introduced by vaccination, one other important issue
related to miRNA regulation and pG4s arises. In miRNA structures,
hundreds of pG4 sequences are identified (Rouleau et al., 2018). In theirunfolded conformation, as during binding to their respective targets in 3′
to 5′ sequences of mRNAs, miRNAs switch off the translation of theirrespective target mRNA. Alternatively, when in the presence of a G4
ligand, the translation of their target mRNAs is promoted (Chan et al.,2018). Moreover, a vast number of putative miRNA binding sites overlap
with G4s in 3’ UTRs of mRNAs as there are at least 521 specific miRNAs
that are predicted to bind to at least one of these G4s. Overall, 44,294
potential G4-miRNA binding sites have been traced to possess putative
overlapping G4s in humans (Rouleau et al., 2017).
As described elsewhere, during the cellular translation of vaccine
mRNAs, an increased assembly of a number of RNA binding protein
helicases, such as eIF4A bound to eIF4G, will occur (Kyriakopoulos andMcCullough, 2021). The presence of increased pG4s in synthetic mRNAs
can potentially amplify binding of RNA binding proteins and miRNAs.
This form of molecular crowding of protein components (helicases) withgreat affinity for G4 binding (Rouleau et al., 2017) will decrease thenumber of RNA binding proteins binding G4s normally available for
miRNA regulation. This loss of RNA binding proteins as well as miRNAavailability for regulation by binding to G4s can dramatically alter thetranslational regulation of miRNAs present in cells and thereby disrupt
essential regulation of oncogene expression. An example is the
p16-dependent regulation of the p53 tumor suppressor protein (Rouleau
et al., 2017; Al-Khalaf and Aboussekhra, 2018).
This process is exceedingly complicated yet tantamount to cellular
homeostasis. So, again, it merits summarizing. If pG4s accumulate, as
would be expected with an increased amount of GC content in thevaccine mRNA, this would have an effect of increasing potential G4
structures available during translation events and this can affect miRNApost-transcriptional regulation. This, in turn, would either favor greater
expression of the oncogenes related to a range of cancers, or drive cells
towards apoptosis and cell death (Weldon et al., 2018). The case study
described earlier in this paper strongly supports the hypothesis thatthese injections induce accelerated lymphoma progression in follicular
B-cells (Goldman et al., 2021).
miRNA binding recognition patterns are imperfectly complementary
to their target regions, and for this reason they are referred to as “master
regulators,” since one miRNA affects a plethora of different targets(Rouleau et al., 2018). The multitude of pG4s in the mRNA of the vac­cine would predictably act as decoys, distracting miRNAs from theirnormal function in regulating human protein expression. The increase in
G4 targets due to the vaccine would decrease the availability of miRNAs
to target human-expressed G4s for regulation of gene expression. Thiscan result in downregulation of miRNA expression which is implicatedin cardiovascular pathology (Small and Olson, 2011), onset of neuro­
degeneration (Abe and Bonini, 2013), and/or cancer progression (Farazi
et al., 2013).
In most respects within epitranscriptomic machinery, miRNAs are

involved in translation repression. One example, vital for cellular
normal housekeeping, is that of Mouse double minute 2 homolog(MDM2), a physical negative regulatory protein of p53. P53 itself isconsidered the master regulator of the cellular tumor suppression
network of genes. P16 controls the expression of many miRNAs, and, via
miR-141 and mIR-146b-5p binding to MDM2 mRNA, it induces thenegative regulation of MDM2, thus enabling p53 ubiquitination andpromotion of cell survival upon DNA damage events (Al-Khalaf andAboussekhra, 2018). Dysregulation of miRNAs that control MDM2
suppression of p53 would predictably lead to an increased risk to a rangeof cancers (Ozaki and Nakagawara, 2011).
5. Type I IFNs and COVID-19
Type I IFNs play an essential role in fighting viral infections, anddeficiencies in type I IFN signaling have been associated with pooroutcomes from COVID-19 in multiple studies. These cases are often
associated with autoantibodies to type I IFNs. As reviewed below, type I
IFNs have been used with some success in treating severe COVID-19,
particularly if administered very early in the disease process. If, asargued above, the mRNA vaccines interfere with type I IFN signaling,
this could lead to increased susceptibility to COVID-19 in the two weeks
following the first vaccine, before an antibody response has been
initiated.
Cells infected with a virus detect the presence of virus replication
through a number of pattern recognition receptors (PRRs), which serve
as sentinels sensing aberrant RNA structures that often form during viral
replication. These receptors respond by oligomerizing and subsequently
inducing type I IFNs, ultimately upregulating a large number of proteins
involved in suppressing viral proliferation (Janeway and Medzhitov,2002).
A multi-author study by researchers in Paris, France, involving acohort of 50 COVID-19 patients with varying degrees of disease severity,
revealed that patients with severe disease were characterized by a highly
impaired type I IFN response (Hadjadj et al., 2020). These patients had
essentially no IFN-β and low IFN-α production and activity. This was
associated with a persistent blood viral load and an exacerbated in­flammatory response, characterized by high levels of tumor necrosis
factor α (TNF-α) and Il-6. The authors proposed type I IFN therapy as apotential treatment option. A paper by several researchers in the UnitedStates also identified a unique and inappropriate inflammatory response
in severe COVID-19 patients, characterized by low levels of both type I
and type III IFNs along with elevated chemokines and elevated expres­sion of Il-6 (Blanco-Melo et al., 2020).
Type I IFNs have even been proposed as a treatment option for severe
COVID-19. In a hamster model, researchers exposed hamsters to SARSCoV-2 and induced an inflammatory response in the lungs and systemic
inflammation in distal tissues. They found that intranasal administrationof recombinant IFN-α resulted in a reduced viral load and alleviation ofsymptoms (Hoagland et al., 2021). A retrospective cohort study of 446
COVID-19 patients determined that early administration of IFN-α2b was
associated with reduced in-hospital mortality. However, late IFN ther­apy increased mortality and delayed recovery, revealing that earlyadministration of interferon therapy is essential for a favorable response(Wang et al., 2020a).
A surprising number of people have neutralizing autoantibodies
against type I IFNs, although the underlying etiology of this phenome­
non is not understood. A study using longitudinal profiling of over
600,000 peripheral blood mononuclear cells and transcriptome
sequencing from 54 patients with COVID-19 and 26 controls found anotable lack of type I IFN-stimulated gene responses in myeloid cells
from patients with critical disease (van der Wijst et al., 2021).
Neutralizing autoantibodies against type I IFNs were found in 19% of
patients with critical disease, 6% of patients with severe disease, and 0%of patients with moderate disease. Another study based in Madrid, Spain
revealed that 10% of patients with severe COVID-19 disease had
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autoimmune antibodies to type I IFNs (Troya et al., 2021). A
multi-author study based in France found that COVID-19 mortality wassignificantly more frequent in patients with neutralizing autoantibodies
against type I interferon than those without neutralizing antibodies(55% vs. 23%) (Chauvineau - Grenier et al., 2022). Finally, Stertz andHale (2021) note that, whether due to autoantibodies or perhaps
loss-of-function polymorphisms associated with interferon systemgenes, deficiencies in interferon production are associated with as manyas 15% of all life-threatening COVID-19 cases.

extracellular vesicles (EVs) that are constantly released by one cell andlater taken up by another cell, which could be in a distant organ. Smallvesicles known as exosomes, formed inside endosomes, are similar insize to viruses, and are released through exocytosis into the extracellularspace to subsequently circulate throughout the body (Yoshikawa et al.,2019). Exosomes can deliver a diverse collection of biologically active
molecules, including mRNA, microRNAs (miRNAs), proteins, and lipids(Ratajczak and Ratajczak, 2016). During a viral infection, infected cells
secrete large quantities of exosomes that act as a communication
network among the cells to orchestrate the response to the infection(Chahar et al., 2015).
In a collaborative effort by a team of researchers from Arizona andConnecticut, it was found that people who were vaccinated with themRNA vaccines acquired circulating exosomes containing the SARSCoV-2 spike glycoprotein by day 14 following vaccination (Bansal
et al., 2021). They also found that there were no circulating antibodies
to the spike glycoprotein fourteen days after the first vaccine. After thesecondvaccine,however,thenumberof
circulating
spike-glycoprotein-containing exosomes increased by up to a factor of
12. Furthermore, antibodies first appeared on day 14. The exosomespresented spike glycoprotein on their surface, which, the authors
argued, facilitated antibody production. When mice were exposed to
exosomes derived from vaccinated people, they developed antibodies tothe spike glycoprotein. Interestingly, following peak expression, thenumber of circulating spike-glycoprotein-containing exosomes
decreased over time, in step with the decrease in the level of antibodies
to the spike glycoprotein.
Exosomes exist as a part of the mRNA decay mechanism in close
association under stress conditions with stress granules (SGs) and Pbodies (PBs) (Decker and Parker, 2012; Kothandan et al., 2020). Underconditions of vaccine-mRNA-induced translation, which could be called“excessive dependence on cap-dependent translation,” there is an
obvious resistance to promotion and assembly of the large decapping
complex (Kyriakopoulos and McCullough, 2021), and therefore resis­
tance against physiological mRNA decay processes (Decker and Parker,2012). This would mean that the fate of particular synthetic mRNAs that
otherwise would be determined by the common cellular strategy formRNA turnover involving messenger ribonucleinproteins (mRNPs) is
being omitted (Borbolis and Syntichaki, 2015).
Furthermore, under conditions of over-reliance on cap-dependenttranslation by the synthetic mRNAs in SARS-CoV-2 vaccines (Kyr­iakopoulos and McCullough, 2021), many native mRNAs holding
considerable IRES and specific methylations (m6A) in their structure
will favorably choose cap-independent translation, which is strongly
linked to mRNA decay quality control mechanisms (Han and Choe,
2020). In this sense, considerable deadenylated mRNA products as wellas products derived from mRNA metabolism (decay) are directly linked
to exosome cargoes (Borbolis and Syntichaki, 2015).
An example of dependence on cap-dependent translation is describedin T-cell acute lymphoblastic leukaemia (T-ALL). Due to mechanistic
target of rapamycin C (mTORC)-1 over-functioning in T-ALL, the cells
are driven completely towards cap-dependent translation (Girardi and
De Keersmaecker, 2015). An analogous condition is described by Kyr­
iakopoulos and McCullough (2021). Even in this highly aggressive
cancerous state, during inhibition of cap-dependent translation in T-ALL
cells, there is a rapid reversion to cap-independent translation (Girardi
and De Keersmaecker, 2015). Similarly, a picornavirus infection (Janget al., 1990) drives cells towards cap-independent translation due toinhibition of components of eIF4F complex and pluralism of IRES in viralRNA.
In humans, there is an abundance of mostly asymptomatic picorna­
virus infections like the Safford Virus with an over 90% seroprevalencein young children and adults (Zoll et al., 2009). In either case, whether
an apoptotic event due to a stress-like condition (Rusk, 2008) or anmRNA-cap-driven-like carcinomatous effect (De Paolis et al., 2021), themiRNA levels will be increased due to the increased epitranscriptomic

6. Are the methylation strategies for cellular housekeeping
generally omitted by vaccine mRNAs?
Methylation of mRNAs has been evolutionarily devised to control
translation of transcripts and therefore expression of genes by a complex
cascade of methylator (writers), de-methylator (eraser) and reader
proteins. Adenosine methylation is the most abundant epitranscriptomic
mRNA modification, and it occurs at multiple sites across the mRNA
molecule (Zaccara et al., 2019). A key methylation of adenosine“N6-methyladenosine (m6A)” specifically in the 5′ UTR of mRNAs reg­ulates normal cell physiology, the inflammatory response and cancer
progression. The role and mechanisms of m6A in human disease isextensive, and it is excellently covered in other comprehensive reviews(Yang et al., 2020; Knuckles and Bühler, 2018). Foremost among these,
the SARS-CoV-2 molecular vaccination induces cell stress conditions, as
is described by the elevated NF-κB signaling after vaccination (Liu et al.,2021; Koo et al., 2010).
Under conditions of cellular stress, which can be induced by a viral
infection or disease states such as cancer, m6A mediates mRNAs toundergo translation preferentially in a cap-independent way (Meyer
et al., 2015). As discussed previously, this is opposite to the impact ofmRNA SARS-CoV-2 vaccination, which drives cells toward a cap-de­pendent translation. Furthermore, under diversified conditions ofcellular stress, there is an overwhelming induction oftranscriptome-wide addition of m6A that causes an increased number ofmRNAs to possess 5′ UTRs enriched with m6A (Meyer et al., 2015).
Eukaryotic translation initiation factor 4E (eIF4E) is the initial
mRNA cap-binding protein that directs ribosomes to the cap structure ofmRNAs, in order to initiate translation into protein. The dependence on
cap-dependent translation of vaccine mRNAs will consume a surplus ofeIF4E availability needed to translate an unnaturally high number ofsynthetic mRNAs. However, cap-independent translation takes place
without requiring eIF4E to be bound to eIF4F. The competition for ri­
bosomes will shift towards the cap-independent translation of tran­
scripts, since the mRNAs undergoing cap-independent translation are
equipped, apart from internal ribosome entry sites (IRES), with special
binding motifs that bind to factors that actively recruit mRNAs to theribosome cap-independent translational enhancers (CITEs) (Shatsky
et al., 2018).
Furthermore, this also means that eIF4E, which is a powerful onco­
gene regulator and cell proliferation modulator, will sustain its activities
by this competition for an unnaturally prolonged period of time, trying
to counterbalance the competition between robustly-capped mRNAs in
vaccines and IRES-containing mRNAs (Kyriakopoulos and McCullough,2021; Svitkin et al., 2005). This type of condition results in dysregula­tion of co-transcriptional m6A mRNA modifications and seriously links
to molecular progressions of various cancers (Han and Choe, 2020), as
well as creating predisposing conditions for subsequent viral infections(Svitkin et al., 2005).
We next consider the impact of mRNA-vaccination-derived SARSCoV-2 spike glycoprotein on the cellular IFN system via massive exo­
some production.
7. Exosomes and MicroRNAs
An important communication network among cells consists of7

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cause vocal cord paralysis associated with difficulty swallowing(dysphagia) difficulty speaking (dysphonia) and/or shortness of breath(dyspnea) (Gould et al., 2019; Erman et al., 2009). We will return tothese specific pathologies in our review of VAERS data below.
HEK293 cells were originally derived from cultures taken from thekidney of a human fetus several decades ago and immortalized throughinfection with adenovirus DNA. While they were extracted from thekidney, the cells show through their protein expression profile that they
are likely to be of neuronal origin (Shaw et al., 2002). This suggests thatneurons in the vagus nerve would respond similarly to the SARS-CoV-2
spike glycoprotein. Thus, the available evidence strongly suggests that
endogenously produced SARS-CoV-2 spike glycoprotein creates adifferent microRNA profile than does natural infection with
SARS-CoV-2, and those differences entail a potentially wide range ofdeleterious effects.
A central point of our analysis below is the important distinction
between the impact of vaccination versus natural infection on type I IFN.
While vaccination actively suppresses its production, natural infection
promotes type I IFN production very early in the disease cycle. Thosewith preexisting conditions often exhibit impaired type I IFN signaling,which leads to more severe, critical, and even fatal COVID-19. If theimpairment induced by the vaccine is maintained as antibody levels
wane over time, this could lead to a situation where the vaccine causes amore severe disease expression than would have been the case in theabsence of the vaccine.
Another expected consequence of suppressing type I IFN would bereactivation of preexisting, chronic viral infections, as described in
Section 9.

functioning and enhanced mRNA decay. Because of the high demand forgene expression, high levels of certain miRNAs will be expected to becontained in exosomes via P bodies (Yu et al., 2016).
Also, under conditions of overwhelming production of SARS-CoV-2
spike glycoprotein due to SARS-CoV-2 molecular vaccination, it wouldof course be expected that a significant proportion of over-abundant
intracellular spike glycoproteins would also be exported via exosome
cargoes (Wei et al., 2021).
Mishra and Banerjea (2021) investigated the role of exosomes in thecellular response of SARS-CoV-2 spike-transfected cells. They wrote in
the abstract:“We propose that SARS-CoV-2 gene product, Spike, is able to modify
the host exosomal cargo, which gets transported to distant unin­
fected tissues and organs and can initiate a catastrophic immune
cascade within Central Nervous System (CNS).”
Their experiments involved growing human HEK293T cells in cul­
ture and exposing them to SARS-CoV-2 spike gene plasmids, which
induced synthesis of spike glycoprotein within the cells. They foundexperimentally that these cells released abundant exosomes housing
spike glycoprotein along with specific microRNAs. They then harvested
the exosomes and transferred them to a cell culture of human microglia(the immune cells that are resident in the brain). They showed that the
microglia readily took up the exosomes and responded to the microRNAs
by initiating an acute inflammatory response. The role of microglia incausing neuroinflammation in various viral diseases, such as Human
Immunodeficiency Virus (HIV), Japanese Encephalitis Virus (JEV), andDengue, is well established. They proposed that long-distance cell-cellcommunication via exosomes could be the mechanism by which
neurological symptoms become manifest in severe cases of COVID-19.
In further exploration, the authors identified two microRNAs thatwere present in high concentrations in the exosomes: miR-148a andmiR-590. They proposed a specific mechanism by which these two
microRNAs would specifically disrupt type I interferon signaling,
through suppression of two critical proteins that control the pathway:ubiquitin specific peptidase 33 (USP33) and IRF9. Phosphorylated
STAT1 and STAT2 heterodimers require IRF9 in order to bind IFNstimulated response elements, and therefore IRF9 plays an essential
role in the signaling response. The authors showed experimentally thatmicroglia exposed to the exosomes extracted from the HEK293 culture
had a 50% decrease in cellular expression of USP33 and a 60% decreasein IRF9. They further found that miR-148a specifically blocks USP33 andmiR-590 specifically blocks IRF9. USP33 removes ubiquitin from IRF9,and in so doing it protects it from degradation. Thus, the two microRNAs
together conspire to interfere with IRF9, thus blocking receptor response
to type I interferons.
A study by de Gonzalo-Calvo et al. (2021) looked at the microRNA
profile in the blood of COVID-19 patients and their quantitative variancebased upon disease severity. Multiple miRNAs were found to be up- anddown-regulated. Among these was miR-148a-3p, the guide strand pre­cursor to miR-148a. However, miR-148a itself was not among the
microRNAs catalogued as excessive or deficient in their study, nor was
miR-590. It appears from these findings that miR148a and miR-590 andtheir inflammatory effects are unique to vaccination-induced SAR­
S-CoV-2 spike glycoprotein production.
Tracer studies have shown that, following injection into the arm
muscle, the mRNA in mRNA vaccines is carried into the lymph system byimmune cells and ultimately accumulates in the spleen in high con­centrations (Bahl et al., 2017). Other studies have shown that stressed
immune cells in germinal centers in the spleen release large quantities of
exosomes that travel to the brain stem nuclei along the vagus nerve (asreviewed in Seneff and Nigh (2021)). The vagus nerve is the 10th cranial
nerve and it enters the brainstem near the larynx. The superior andrecurrent laryngeal nerves are branches of the vagus that innervate
structures involved in swallowing and speaking. Lesions in these nerves

8. Impaired DNA repair and adaptive immunity
The immune system and the DNA repair system are the two primarysystems that higher organisms rely on for defense against diverse
threats, and they share common elements. Loss of function of key DNA
repair proteins leads to defects in repair that inhibit the production offunctional B- and T-cells, resulting in immunodeficiency. Nonhomologous end joining (NHEJ) repair plays a critical role inlymphocyte-specific V(D)J recombination, which is essential for pro­ducing the highly diverse repertoire of B-cell antibodies in response to
antigen exposure (Jiang and Mei, 2021). Impaired DNA repair is also a
direct pathway towards cancer.
A paper published by Liu et al., in 2021 monitored several parame­ters associated with immune function in a cohort of patients by con­ducting single-cell mRNA sequencing of peripheral blood mononuclear
cells (PBMCs) harvested from the patients before and 28 days after the
first injection of a COVID-19 vaccine based on a weakened version of thevirus (Liu et al., 2021). While these vaccines are different from themRNA vaccines, they also work by injecting the contents of the vaccine
into the deltoid muscle, bypassing the mucosal and vascular barriers.
The authors found consistent alteration of gene expression following
vaccination in many different immune cell types. Observed increases in
NF-κB signaling and reduced type I IFN responses were further
confirmed by biological assays. Consistent with other studies, theyfound that STAT2 and IRF7 were significantly downregulated 28 days
after vaccination, indicative of impaired type I IFN responses. They
wrote: “Together, these data suggested that after vaccination, at least by
day 28, other than generation of neutralizing antibodies, people’s im­
mune systems, including those of lymphocytes and monocytes, wereperhaps in a more vulnerable state.” (Liu et al., 2021).
These authors also identified disturbing changes in gene expressionthat would imply impaired ability to repair DNA. Up to 60% of the totaltranscriptional activity in growing cells involves the transcription ofribosomal DNA (rDNA) to produce ribosomal RNA (rRNA). The enzymethat transcribes ribosomal DNA into RNA is RNA polymerase I (Pol I).
Pol I also monitors rDNA integrity and influences cell survival (Kakar­
ougkas et al., 2013). During transcription, RNA polymerases (RNAPs)
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actively scan DNA to find bulky lesions (double-strand breaks) andtrigger their repair. In growing eukaryotic cells, most transcription in­volves synthesis of ribosomal RNA by Pol I. Thus, Pol I promotes survival
following DNA damage (Kakarougkas et al., 2013). Many of the down­
regulated genes identified by Liu et al. (2021) were linked to the cell
cycle, telomere maintenance, and both promoter opening and tran­
scription of POL I, indicative of impaired DNA repair processes.
One of the gene sets that were suppressed was due to “deposition of
new CENPA [centromere protein A] containing nucleosomes at thecentromere.” Newly synthesized CENPA is deposited in nucleosomes atthe centromere during late telophase/early G1 phase of the cell cycle.
This points to arrest of the cell cycle in G1 phase as a characteristicfeature of the response to the inactivated SARS-CoV-2 vaccine. Arrest of
pluripotent embryonic stem cells in the G1 phase (prior to replication
initiation) would result in impaired self-renewal and maintenance ofpluripotency (Choi et al., 2013).
Two checkpoint proteins crucially involved in DNA repair andadaptive immunity are BRCA1 and 53BP1, which facilitate both ho­mologous recombination (HR) and NHEJ, the two primary repair pro­
cesses (Zhang and Powell, 2005; Panier and Boulton, 2014). In an in vitro
experiment on human cells, the SARS-CoV-2 full-length spike glyco­
protein was specifically shown to enter the nucleus and hinder the
recruitment of these two repair proteins to the site of a double-strand
break (Jiang and Mei, 2021). The authors summarized their findings
by saying, “Mechanistically, we found that the spike protein localizes in
the nucleus and inhibits DNA damage repair by impeding key DNA
repair protein BRCA1 and 53BP1 recruitment to the damage site.”
Another mechanism by which the mRNA vaccines could interferewith DNA repair is through miR-148. This microRNA has been shown to
downregulate HR in the G1 phase of the cell cycle (Choi et al., 2014). As
was mentioned earlier in this paper, this was one of the two microRNAs
found in exosomes released by human cells following SARS-CoV-2 spikeglycoprotein synthesis in the experiments by Mishra and Banerjea(2021).

facilitating IRF9 degradation (Verweij et al., 2015).
An additional case of viral reactivation is noteworthy as well. It
involved an 82-year-old woman who had acquired a hepatitis C viral(HCV) infection in 2007. A strong increase in HCV load occurred a few
days after vaccination with an mRNA Pfizer/BioNTech vaccine, alongwith an appearance of jaundice. She died three weeks after vaccinationfrom liver failure (Lensen et al., 2021).
10. Immune thrombocytopenia
Immune thrombocytopenia is an autoimmune disorder, where theimmune system attacks circulating platelets. Immune thrombocytopenic
purpura (ITP) has been associated with several vaccinations, including
measles, mumps, rubella (MMR), hepatitis A, varicella, diphtheria,
tetanus, pertussis (DPT), oral polio and influenza (Perricone et al.,2014). While there is broad awareness that the adenovirus DNA-based
vaccines can cause vaccine-induced immune thrombotic thrombocyto­
penia (VITT) (Kelton et al., 2021), the mRNA vaccines are not without
risk to VITT, as case studies have been published documenting suchoccurrences, including life threatening and fatal cerebral venous sinus
thrombosis (Lee et al., 2021; Akiyama et al., 2021; Atoui et al., 2022;
Zakaria et al., 2021). The mechanism is believed to involve VITT anti­
bodies binding to platelet factor 4 (PF4) and forming immune complexes
that induce platelet activation. Subsequent clotting cascades cause theformation of diffuse microclots in the brain, lungs, liver, legs and else­
where, associated with a dramatic drop in platelet count (Kelton et al.,2021). The reaction to the vaccine has been described as being very
similar to heparin-induced thrombocytopenia (HIT), except that heparin
administration is notably not involved (Cines and Bussel, 2021).
It has been shown that the mRNA vaccines elicit primarily an
immunoglobulin G (IgG) immune response, with lesser amounts of IgA
induced (Wisnewski et al., 2021), and even less IgM production (Danese
et al., 2021). The amount of IgG antibodies produced is comparable to
the response seen in severe cases of COVID-19. It is IgG antibodies incomplex with heparin that induce HIT. One can hypothesize that IgG
complexed with the SARS-CoV-2 spike glycoprotein and PF4 is thecomplex that induces VITT in response to mRNA vaccines. It has in fact
been shown experimentally that the receptor binding domain (RBD) of
the spike protein binds to PF4 (Passariello et al., 2021).
The underlying mechanism behind HIT has been well studied,including through the use of humanized mouse models. Interestingly,
human platelets, but not mouse platelets, express the FcγRIIA receptor,
which responds to PF4/heparin/IgG complexes through a tyrosine
phosphorylation cascade to induce platelet activation. Upon activation,platelets release granules and generate procoagulant microparticles.
They also take up calcium, activate protein kinase C, clump together into
microthrombi, and launch a cell death cascade via calpain activation.
These activated platelets release PF4 into the extracellular space, sup­porting a vicious cycle, as this additional PF4 also binds to heparin and
IgG antibody to further promote platelet activation. Thus, FcγRIIA iscentral to the disease process (Nevzorova et al., 2019).
Studies on mice engineered to express the human FcγRIIA receptor
have shown that these transgenic mice are far more susceptible tothrombocytopenia than their wild type counterparts (McKenzie et al.,1999). It has been proposed that platelets may serve an important role inthe clearance of antibody-antigen complexes by trapping the antigen inthrombi and/or carrying them into the spleen for removal by immune
cells. Platelets are obviously rapidly consumed in the process, whichthen results in low platelet counts (thrombocytopenia).
Platelets normally circulate with an average lifespan of only five tonine days, so they are constantly synthesized in the bone marrow andcleared in the spleen. Antibody-bound platelets, subsequent to plateletactivation via Fcγ receptors, migrate to the spleen where they aretrapped and removed through phagocytosis by macrophages (Crow andLazarus, 2003). Fully one third of the body’s total platelets are found in
the spleen. Since the mRNA vaccines are carried into the spleen by

9. Reactivation of varicella-zoster
Type I IFN receptor signaling in CD8+ T cells is critical for the gen­eration of effector and memory cells in response to a viral infection(Kolumam et al., 2005). CD8+ T cells can block reactivation of latent
herpes infection in sensory neurons (Liu et al., 2000). If type I IFN
signaling is impaired, as happens following vaccination but not
following natural infection with SARS-CoV-2, CD8+ T cells’ ability tokeep herpes in check would also be impaired. Might this be the mech­anism at work in response to the vaccines?
Shingles is an increasingly common condition caused by reactivationof latent herpes zoster viruses (HZV), which also causes chicken pox inchildhood. In a systematic review, Katsikas Triantafyllidis et al. (2021)
identified 91 cases of herpes zoster occurring an average of 5.8 days
following mRNA vaccination. While acknowledging that causality is not
yet confirmed, “Herpes zoster is possibly a condition physicians andother healthcare professionals may expect to see in patients receiving
COVID-19 vaccines” (Katsikas Triantafyllidis et al., 2021). In a letter tothe editor published in September 2, 2021, Fathy et al. (2022) reported
on 672 cases of skin reactions that were presumably vaccine-related,
including 40 cases of herpes zoster and/or herpes simplex reac­tivation. These cases had been reported to the American Academy ofDermatology and the International League of Dermatologic Societies’
COVID-19 Dermatology Registry, established specifically to trackdermatological sequalae from the vaccines. There are multiple addi­
tional case reports of herpes zoster reactivation following COVID-19
vaccination in the literature (Psichogiou et al., 2021b; Iwanaga et al.,2021). Lladó et al. (2021) noted that 51 of 52 reports of reactivatedherpes zoster infections happened following mRNA vaccination. Herpes
zoster itself also interferes with IFN-α signaling in infected cells boththrough interfering with STAT2 phosphorylation and through9

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immune cells initially attracted to the injection site in the arm muscle,
thereistremendous
opportunityforthereleaseof
spike-glycoprotein-containing exosomes by dendritic cells in the spleen
synthesizing spike protein. One can speculate that platelet activation
following the formation of a P4F/IgG/spike protein complex in the
spleen is part of the mechanism that attempts to clear the toxic spikeglycoprotein.
We mentioned earlier that one of the two microRNAs highly
expressed in exosomes released by human cells exposed to the SARSCoV-2 spike glycoprotein was miR-148a. miR-148a has been shown
experimentally to suppress expression of a protein that plays a central
role in regulating FcγRIIA expression on platelets. This protein, called Tcell ubiquitin ligand-2 (TULA-2), specifically inhibits activity of theplatelet Fcγ receptor. miR-148a targets TULA-2 mRNA and down­
regulates its expression. Thus, miR-148a, present in exosomes releasedby macrophages that are compelled by the vaccine to synthesize SARSCoV-2 spike glycoprotein, acts to increase the risk of thrombocytopenia
in response to immune complexes formed by spike glycoprotein antigen
and IgG antibodies produced against the spike glycoprotein.

ameliorated steatosis and inflammation (Wang et al., 2013).
Multiple case reports in the research literature describe liver damage
following mRNA vaccines (Zin Tun et al., 2021; Dumortiera, 2022;
Mann et al., 2021). A plausible factor leading to these outcomes is the
suppression of PPAR-α through downregulation of IRF9, and subse­
quently decreased sulfatide synthesis in the liver.
12. Guillain Barré syndrome and neurologic injury syndromes
GBS is an acute inflammatory demyelinating neuropathy associatedwith long-lasting morbidity and a significant risk of mortality (Cr é ange,2000). The disease involves an autoimmune attack on the nerves asso­
ciated with the release of pro-inflammatory cytokines.
GBS is often associated with autoantibodies to sulfatide and othersphingolipids (Ilyas et al., 1991). Activated T-cells produce cytokines in
response to antigen presentation by macrophages, and these cytokines
can induce autoantibody production through epitope spreading (Van­derlugt and Miller, 2002). The antibodies, in turn, induce complement
activation, which causes demyelination and axonal damage, leading tosevere injury to peripheral neurons (Kuwahara and Kusunoki, 2018).
The SARS-CoV-2 spike glycoprotein has been shown to bind to heparansulfate, which is a sulfated amino-sugar complex resembling the sulfatedgalactose in sulfatide (Kalra and Kandimalla, 2021). Thus, it isconceivable that the spike glycoprotein also binds to sulfatide, and thismight trigger an immune reaction to the spike-glycoprotein-sulfatide
complex.
As described in the previous section, impaired sulfatide synthesis in
the liver due to suppression of IRF9 will lead to systemic sulfatide
deficiency over time. Sulfatide deficiency can have major impact in thebrain and nervous system. Twenty percent of the galactolipids found in
the myelin sheath are sulfatides. Sulfatide is a major component of thenervous system, found in especially high concentrations in the myelin
sheath in both the peripheral and the central nervous system. De­
ficiencies in sulfatide can lead to muscle weakness, tremors, and ataxia(Honke, 2013), which are common symptoms of GBS. Chronic neuro­
inflammation mediated by microglia and astrocytes in the brain leads todramatic losses of brain sulfatide, and brain deficiencies in sulfatide area major feature of Alzheimer’s disease (Qiu et al., 2021). Mice with adefect in the ability to synthesize sulfatide from ceramide show an
impaired ability to maintain the health of axons as they age. Over time,they develop redundant, uncompacted and degenerating myelin sheaths
as well as deteriorating structure at the nodes of Ranvier in the axons,causing the loss of a functionally competent axoglial junction (Marcus
et al., 2006).
Angiotensin II (Ang II), in addition to its profound effects on car­diovascular disease, also plays a role in inflammation in the brain
leading to neurodegenerative disease (Lanz. et al., 2010). The
SARS-CoV-2 spike glycoprotein contains a unique furin cleavage site notfound in SARS-CoV, which allows the extracellular enzyme furin to
detach the S1 segment of the spike glycoprotein and release it into cir­
culation (Letarov et al., 2021). S1 has been shown to cross the
blood-brain barrier in mice (Rhea et al., 2021). S1 contains the receptor
binding domain that binds to ACE2 receptors, disabling them. When
ACE2 receptor signaling is reduced, Ang II synthesis is increased. Neu­rons in the brain possess ACE2 receptors that would be susceptible todisruption by S1 released from spike-glycoprotein-containing exosomesor spike-glycoprotein-producing cells that had taken up the nano­particles in the vaccines. Ang II enhances TLR4-mediated signaling in
microglia, inducing microglial activation and increasing the productionof reactive oxygen species leading to tissue damage, within the para­
ventricular nucleus in the brain (Rodriguez-Perez et al., 2015).
Elevated levels of Ang II is a causal factor in neurodegeneration of
the optic nerve, causing optic neuritis, which can result in severe irre­
versible visual loss (Guo et al., 2017). Multiple case reports havedescribed cases of optic neuropathy appearing shortly after mRNA
vaccination for COVID-19 (Maleki, 2021; Barone et al., 2021). Other

11. PPAR-α, sulfatide and liver disease
As we have already stated, an experiment by Mishra and Banerjea(2021) demonstrated that the SARS-CoV-2 spike glycoprotein induces
the release of exosomes containing microRNAs that specifically interferewith IRF9 synthesis. In this section we will show that one of the con­sequences of suppression of IRF9 would be reduced synthesis of sulfatidein the liver, mediated by the nuclear receptor peroxisome
proliferator-activated receptor α (PPAR-α).
Sulfatides are major mammalian serum sphingoglycolipids which aresynthesized and secreted mainly from the liver (Lu et al., 2019). They
are the only sulfonated sphingolipids in the body. Sulfatides are formed
by a two-step process involving the conversion of ceramide to gal­
actocerebroside and its subsequent sulfation. Sulfatide is expressed on
the surface of platelets, erythrocytes and lymphocytes. Serum sulfatides
exert both anti-coagulative and anti-platelet-activation functions. The
enzyme in the liver that synthesizes sulfatide, cerebroside sulfo­
transferase, has specifically been found to be induced by activation of
PPAR-α in mice (Kimura et al., 2012). Therefore, reduced expression of
PPAR-α leads to sulfatide deficiency.
PPAR-α ligands exhibit anti-inflammatory and anti-fibrotic effects,
whereas PPAR-α deficiency leads to hepatic steatosis, steatohepatitis,
steatofibrosis, and liver cancer (Wang et al., 2020b). In 2019, an
experiment was conducted by a team of researchers in Japan on micewith a defective gene for PPAR-α (Lu et al., 2019). These mice, when fed
a high cholesterol diet, were susceptible to excess triglyceride accumu­
lation and exacerbated inflammation and oxidative stress in the liver,along with increased levels of coagulation factors. The mice also man­ifested with decreased levels of sulfatides in both the liver and theserum. The authors hypothesized that cholesterol overload exerts its
toxic effects in part by enhancing thrombosis, following abnormal he­
patic lipid metabolism and oxidative stress. They showed that PPAR-α
can attenuate these toxic effects through transcriptional regulation of
coagulation factors and upregulation of sulfatide synthesis, in addition
to its effects in ameliorating liver disease. They proposed that therapies
such as fibrates aimed at activating PPAR-α might prevent
high-cholesterol-diet-induced cardiovascular disease.
Tracer studies have shown that the mRNA from mRNA vaccines
migrates preferentially to the liver and spleen, reaching higher con­centration there than in any other organs (Bahl et al., 2017). Thus, there
is potential for suppression of IRF9 in the liver by the vaccine. IRF9 ishighly expressed in hepatocytes, where it interacts with PPAR-α, acti­
vating PPAR-α target genes. A study on IRF9 knockout mice showed thatthese mice developed steatosis and hepatic insulin resistance when
exposed to a high-fat diet. In contrast, adenoviral-mediated hepatic IRF9
overexpression in obese mice improved insulin sensitivity and
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debilitating neurological conditions are also appearing shortly after
vaccination, where a causal relationship is suspected. A case study basedin Europe tracking neurological symptoms following COVID-19 vacci­
nation identified 21 cases developing within a median of 11 days
post-vaccination. The cases had diverse diagnoses including cerebral
venous sinus thrombosis, nervous system demyelinating diseases, in­flammatory peripheral neuropathies, myositis, myasthenia, limbic en­
cephalitis, and giant cell arteritis (Kaulen et al., 2021). Khayat-Khoei
et al. (2021) describe a case series of 7 patients, ages ranging from 24 to
64, presenting with demyelinating disease within 21 days of a first or
second mRNA vaccination. Four had a prior history of (controlled) MS,
while three were previously healthy.
Hearing loss and tinnitus are also well-known side effects of COVID19. A case study involved a series of ten COVID-19 patients who sufferedfrom audiovestibular symptoms such as hearing loss, vestibular
dysfunction and tinnitus (Jeong et al., 2021). The authors demonstrated
that human inner ear tissue expresses ACE2, furin and the trans­
membrane protease serine 2 (TMPRSS2), which facilitates viral entry.
They also showed that SARS-CoV-2 can infect specific human inner ear
cell types.
Another study evaluating the potential for the SARS-CoV-2 virus toinfect the ear specifically examined expression of the receptor ACE2 andthe enzymes furin and TM-PRSS2 various types of cells in the middle andinner ears of mice. They found that ACE2 and furin were “diffusely
present in the eustachian tube, middle ear spaces, and cochlea, sug­gesting that these tissues are susceptible to SARS-CoV-2 infection.”(Uranaka et al., 2021). Tinnitus is positively associated with hyperten­
sion, which is induced by elevated levels of Ang II (Rodrigues Figueiredo
et al., 2016).
Headache is a very common adverse reaction to the COVID-19 mRNA
vaccines, particularly for people who are already susceptible to head­aches. In a study based on a questionnaire involving 171 participants,
the incidence of headaches was found to be 20.5% after the first vaccine,rising to 45.6% after the second shot (Sekiguchi et al., 2021). A casestudy described a 37-year-old woman suffering from a debilitating
migraine attack lasting for 11 days following the second Pfizer/BioNtechmRNA vaccine (Consoli et al., 2021).
Steroids are often used as adjunct therapy to treat migraine (Huang
et al., 2013). Dexamethasone and other steroids stimulate PPAR-α re­
ceptors in the liver through the steroid receptor, thus offsetting the ef­
fects of IRF9 suppression (Lemberger et al., 1994). A theory for theorigins of migraine involves altered processing of sensory input in thebrainstem, primarily trigeminal neurons (Dodick and Silberstein, 2006).
The trigeminal nerve is in close proximity to the vagus nerve in thebrainstem, so spike-glycoprotein-carrying exosomes could easily reach it
along the vagal route. Magnetic resonance imaging has revealed thatstructural changes in the trigeminal nerve reflecting aberrant micro­
structure and demyelination are a characteristic feature of people who
suffer from frequent migraine headaches (Mungoven et al., 2020). A
potential factor linked to either SARS-CoV-2 infection or mRNA vacci­
nation is an excessive level of Ang II in the brainstem due to SARS-CoV-2
spike glycoprotein inhibition of ACE2 receptors. ACE inhibitors and Ang
II receptor antagonists have become popular drugs to treat migraine
headaches off-label (Tronvik et al., 2003; Nandha and Singh, 2012).
Migraine headache could thus arise from both the spike glycoprotein’s
disruption of ACE2 receptors and the destruction of the myelin sheathcovering critical facial nerves through a microglial inflammatory
response and loss of sulfatide. The source of that spike glycoprotein
could be either exogenous or endogenous.

the literature involved a 36-year-old man who developed weakness in
the left arm one day after vaccination, progressing to numbness andtingling in the arm and subsequent symptoms of Bell’s palsy over the
next few days. A common cause of Bell’s palsy is reactivation of herpes
simplex virus infection centered around the geniculate ganglion (Eviston
et al., 2015). This, in turn, can be caused by disruption of type I IFN
signaling.
14. Myocarditis
There has been considerable media attention devoted to the fact that
COVID-19 vaccines cause myocarditis and pericarditis, with anincreased risk in particular for men below the age of 50 (Simone et al.,2021; Jain et al., 2021). The SARS-CoV-2 spike glycoprotein has been
demonstrated to injure cardiac pericytes, which support the capillaries
and the cardiomyocytes (Avolio et al., 2020). Myocarditis is associatedwith platelet activation, so this could be one factor at play in the
response to the vaccines (Weikert. et al., 2002). However, another factor
could be related to exosomes released by macrophages that have taken
up the mRNA nanoparticles, and the specific microRNAs found in those
exosomes.
A study involving patients suffering from severe COVID-19 disease
looked specifically at the expression of circulating microRNAs comparedto patients suffering from influenza and to healthy controls. One
microRNA that was consistently upregulated in association with COVID19 was miR-155, and the authors suggested that it might be a predictor
of chronic myocardial damage and inflammation. By contrast, influenza
infection was not associated with increased miR-155 expression. They
concluded: “Our study identified significantly altered levels of cardiacassociated miRs [microRNAs] in COVID-19 patients indicating astrong association of COVID-19 with cardiovascular ailments andrespective biomarkers” (Garg et al., 2021).
A study comparing 300 patients with cardiovascular disease tohealthy controls showed a statistically significant increase in circulatinglevels of miR-155 in the patients compared to controls. Furthermore,those with more highly constricted arteries (according to a Gensiniscore) had higher levels than those with lesser disease (Qiu and Ma,2018).
Importantly, exosomes play a role in inflammation in association
with heart disease. During myocardial infarction, miR-155 is sharply
upregulated in macrophages in the heart muscle and released into theextracellular milieu within exosomes. These exosomes are delivered tofibroblasts, and miR-155 downregulates proteins in the fibroblasts that
protect from inflammation and promote fibroblast proliferation. The
resulting impairment leads to cardiac rupture (Wang et al., 2017b).
We have already discussed how the S1 segment of the SARS-CoV-2
spike glycoprotein can be cleaved by furin and released into circula­tion. It binds to ACE2 receptors through its receptor binding domain(RBD), and this inhibits their function. Because ACE2 degrades Ang II,
disabling ACE2 leads directly to overexpression of Ang II, further
enhancing risk to cardiovascular disease. AngII-induced vasoconstric­tion is an independent mechanism to induce permanent myocardial
injury even when coronary obstruction is not present. Repeated episodesof sudden constriction of a cardiac artery due to Ang II can eventuallylead to heart failure or sudden death (Gavras and Gavras, 2002). Fatalcases of COVID-19 vaccination have been described (Choi et al., 2021;
Verma et al., 2021).
ACE2 suppression had already been seen in studies on the original
SARS-CoV virus. An autopsy study on patients succumbing to SARS-CoV
revealed an important role for ACE2 inhibition in promoting heartdamage. SARS-CoV viral RNA was detected in 35% of 20 autopsied
human heart samples taken from patients who died. There was a marked
increase in macrophage infiltration associated with myocardial damage
in the patients whose hearts were infected with SARS-CoV. Importantly,
the presence of SARS-CoV in the heart was associated with marked
reduction in ACE2 protein expression (Oudit et al., 2009).

13. Bell’s palsy
Bell’s palsy is a common cranial neuropathy causing unilateral facial
paralysis. Even in the Phase III clinical trials, Bell’s palsy stood out, withseven cases appearing in the treatment arm as compared to only one in
the placebo group (FDA, 2021a; FDA, 2021b). A case study reported in
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15. Considerations regarding the Vaccine Adverse Event
Reporting System (VAERS)

represents less than 9% of the COVID-19 reports, and its reaction profile
is surely much more similar to that of the mRNA vaccines than to that of
all the other vaccines.
The total number of adverse event reports for COVID-19 injections is
far greater than the cumulative number of annual vaccine adverse event
reports combined in all prior years, as shown by Rose (2021). The
influenza vaccine is a good one to compare against. Given that the
protocol for the mRNA vaccines requires two doses, and that many were
persuaded to receive a booster shot as well, it is clear that the sheer
number of COVID-19 vaccines administered is large compared to othervaccines. We can actually estimate what percent of the adverse reactionsin 2021 would be expected to be associated with COVID-19 vaccines if
the likelihood of an adverse reaction were similar to that of the influenza
vaccine. The CDC tells us that 52% of the US population received a flu
shot in 2021. The USAFacts web site provides percentages of the US
population that received one, two or three doses of COVID-19 vaccines
as a function of time (see: https://usafacts.org/visualizations/c
ovid-vaccine-tracker-states/). The numbers they report for December
30, 2021 are 73% single dose, 62% fully vaccinated, and 21% boosted.
This tallies up to 156% of the population as the total number of
COVID-19 vaccines administered. This is exactly three times as many
COVID vaccines as flu shots.
From VAERS, one can easily obtain the total number of adverse re­actions associated with COVID-19 vaccines, the total number associatedwith flu vaccines, and the total number associated with all vaccines, for
the US-restricted VAERS data from 2021. These come out as: COVID-19:
737,587, FLU: 9,124, and ALL: 792,935. First, we can observe that 93%
of all the events reported were linked to COVID-19 vaccines. If weremove the counts for COVID-19 and replace them with three times thecounts for flu (since COVID-19 vaccines were administered three times
as often), we find that COVID-19 should have accounted for 32.6% of all
the events, which can be compared with the actual result, which is 93%.
We can also conclude that any event that shows up more than 93% asoften for COVID-19 vaccines as for all other vaccines is especially sig­
nificant as a potential toxic effect of these vaccines. Finally, we find that
there are 27 times as many reports for COVID-19 vaccines as would be
expected if its adverse reactions were comparable to those from the flu
vaccine.

The Food and Drug Administration’s Vaccine Adverse Event
Reporting System (VAERS) is an imperfect but valuable resource for
identifying potential adverse reactions to vaccines. Established throughcollaboration between the CDC and FDA, VAERS is “a national early
warning system to detect possible safety problems in U.S.-licensed
vaccines.” According to the CDC it is “especially useful for detecting
unusual or unexpected patterns of adverse event reporting that might
indicate a possible safety problem with a vaccine.” (https://vaers.hhs.
gov/about.html) Even the CDC recognizes that adverse events re­ported to VAERS represent “only a small fraction of actual adverse
events” (Vaers Home, 2021). A widely cited report noted that fewer than
1% of all vaccine-related adverse events are reported to VAERS (Lazarus
et al., 2010). That assertion, though, has no citation so the basis for theclaim is unclear. Rose (2021) published a much more sophisticatedanalysis of VAERS data to offer an estimate of underreporting by a factorof 31 (Rose, 2021). While it is impossible to determine underreportingwith precision, the available evidence is that underreporting verystrongly characterizes the VAERS data. The information presented
below should be understood in that light.
In mining VAERS for ‘signals’ that might indicate adverse reactions(AEs) to mRNA vaccinations, we acknowledge that no report to VAERS
establishes a causal link with the vaccination. That said, the possibilityof a causal relationship is strengthened through both the causal path­ways we have described in this paper, and the strong temporal associ­ation between injections and reported AEs. Nearly 60% of all mRNAinjection-related -AEs have happened within 48 h of injection(https://medalerts.org/vaersdb/findfield.php?TABLE=ON&GROU
P1=ONS&EVENTS=ON&VAX=COVID19&VAXTYPES=COVID-19&S
TATE=NOTFR).
Two important cautions regarding analysis of VAERS data should be
noted. The first is that, in addition to health care professionals submit­ting reports, VAERS is open for public submissions as well. Members of
the public may lack the skills necessary to evaluate a symptom appro­
priately to determine if it merits a VAERS entry. A second caution is thatpublic access also allows for the possibility of anti-vaccination activists
to populate VAERS with false reports to exaggerate the appearance of AE
risk.
An interim analysis of deaths cited previously found that healthservice employees were the VAERS reporter in 67% of reports analyzed(Nandha and Singh, 2012), suggesting a large portion of VAERS reports
are submitted by medical professionals and not the public. This finding
also belies the notion that anti-vaccination activists are filing an exces­
sive number of egregious reports of vaccine injury.
All of the data reported in this section were obtained by querying theonline resource, http://wonder.cdc.gov/vaers.html. Over the 31-year
history of VAERS, up to February 3, 2022, there were a total of
10,321 deaths reported as a “symptom” in association with any vaccine,and 8,241 (80%) of those deaths were linked to COVID-19 vaccines.
Importantly, only 14% of COVID-19 VAERS-reported deaths as of June
2021 could have vaccination ruled out as a cause (McLachlan et al.,2021). This strongly suggests that these unprecedented vaccines exhibit
unusual mechanisms of toxicity that go well beyond what is seen withmore traditional vaccines.
We decided that a reasonable way to characterize the significance ofadverse events linked to COVID-19 vaccines was to focus on events
received in the year 2021, and to compare the counts in the “SYMPTOM”
field for the events associated with COVID-19 vaccines to the total
counts for that same symptom for all vaccines over that same year. In
total, there were 737,689 events reported in VAERS for COVID-19
vaccines in 2021, representing a shocking 93% of the total cases re­ported for any vaccine that same year. While we recognize that some of
the COVID-19 vaccines are based on DNA vector technology rather thanmRNA technology, this class (i.e., the Johnson & Johnson vaccine)

Table 1
Number of symptoms reported in VAERS, restricted to the US population, for theyear 2021, for various adverse effects that could be caused by inflammation inassociated major nerves, showing total counts for COVID-19 vaccines and for all
vaccines.
Symptom

Inflamed Nerve(s)Covid-19
Vaccines

All
Vaccines

Percent
COVID-19

Anosmia
Tinnitus

olfactory nerve
vestibulo-cochlear
nerve
cochlea
facial nerve

3,657
13,275

3,677
13,522

99.5
98.2

2,895
5,881

3,033
6,129

95.5
96.0

vestibular nerve
trigeminal nerve

7,638
8,872

7,819
9,059

97.7
97.9

glossopharyngeal
nerve
several lower cranial
nervesvagus nerve
vagus nerve
vagus nerve
vagus nerve
vagus nerve
–

1,692

1,751

96.6

4,711

4,835

97.4

69,121
27,88539,551
14,701
673
200,552

71,27528,95540,387
15,268699
206,409

97.0
96.3
97.9
96.3
96.3
97.2

Deafness
Bell’s Palsy/
facial palsy
VertigoMigraineheadacheDysphonia
Dysphagia
NauseaVomiting
Dyspnea
Syncope
Bradycardia
TOTAL

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15.1. VAERS data indicative of nerve damage and vagus nerve
involvement

Table 3
Number of symptoms reported in VAERS, restricted to the US population, for theyear 2021, for various indicators of liver disease, showing total counts for
COVID-19 vaccines and for all vaccines.

Table 1 lists a number of symptoms in VAERS that can be associatedwith inflammation of or damage to various major nerves of the body,particularly those in the head. Strikingly, COVID-19 vaccines repre­
sented from 96 to 98% of the reports in the year 2021 related to each ofthese debilitating conditions. There were nearly 100,000 cases of nausea
or vomiting, which are common symptoms of vagus nerve stimulation ordamage (Babic and Browning, 2014). 14,701 cases of syncope linked to
COVID-19 vaccines represented 96.3% of all cases of syncope, awell-established feature of vagus nerve dysfunction (Fenton et al.,2000). There were 3,657 cases of anosmia (loss of smell), clearly
demonstrating that the SARS-CoV-2 spike glycoprotein from the injec­tion in the arm was reaching the olfactory nerve. Dyspnea (shortness ofbreath) is related to vagus nerve impairment in the lungs, and there were39,551 cases of dyspnea connected to COVID-19 vaccines in 2021.
Altogether, these events add up to a total of over 200,000 events,
representing 97.2% of all the entries related to any vaccine in 2021. Thisis also a substantial 27.2% of all the events listed for 2021 in association
with COVID-19 vaccines.
15.2. VAERS data on the heart and liver

15.3. VAERS data related to thrombosis

Percent COVID-19

Myocarditis
ArrestArrhythmia
Myocardial infarction
Cardiac failure
TOTAL

2,322
1,319
1,069
2,224
1,156
8,090

2,361
1,371
1,087
2,272
1,190
8,281

98.3
96.2
98.3
97.9
97.1
97.7

Percent COVID19

Liver disorder[Drug-induced] liver
injury[Acute] hepatic failure
Hepatic cancer[metastatic]
Hepatic cirrhosis
Hepatic cyst
Liver function test
increased
Liver function test
abnormalHepatic function abnormal
Haemangioma of liver
Liver abscessLiver transplant
TOTAL

83
65

87
65

95.4
100

86
12

88
12

97.7
100

67
33
238

69
34
245

97.1
97.0
97.1

90

94

95.7

34
10
7
6
731

34
10
7
6
751

100
100
100
100
97.3

Symptom

Covid-19
Vaccines

All
Vaccines

Percent COVID19

Thrombosis
Deep vein thrombosis
Pulmonary thrombosis
Cerebral thrombosis
Portal vein thrombosis
Superficial veinthrombosis
Peripheral artery
thrombosis
Mesenteric veinthrombosis
Venous thrombosis
TOTAL
Pulmonary embolism

3,899
2,275
631
211
89
81

3,951
2,297
646
215
90
81

98.7
99.0
97.7
98.1
98.9
100

74

74

100

55

56

98.2

41
7,356
3,100

41
7,451
3,137

100
98.7
98.8

15.4. VAERS data related to neurodegenerative disease
Table 5 lists results for several conditions that are linked to neuro­
degenerative disease. Decreased mobility can be caused by Parkinson’s
disease, and there were a striking 8,975 cases listed for 2021 and COVID19 vaccines. Alzheimer’s and Parkinson’s are diseases that normally
Table 5
Number of symptoms reported in VAERS, restricted to the US population, for theyear 2021, for various disorders linked to neurodegenerative disease, showing
total counts for COVID-19 vaccines and for all vaccines.

Table 2
Number of symptoms reported in VAERS, restricted to the US population, for theyear 2021, for various disorders of the heart, showing total counts for COVID-19
vaccines and for all vaccines.
All Vaccines

All
Vaccinestime. Pulmonary embolism, a life-threatening condition that can becaused by a blood clot that travels to the lungs, has a slightly higher
probability of 98.8%, with 3,100 cases listed for COVID-19.

There were 78 unique symptoms in VAERS involving thrombosis,
specifying different arteries and veins. Table 4 shows nine symptoms
with the highest counts, totaling 7,356 events. We investigated the timeinterval for the three dominant ones (thrombosis, deep vein thrombosis
and pulmonary thrombosis), and found that these all have a sharp peakin the 15-30-day range for onset interval (time after vaccination). This
coincides with a sharp peak in pulmonary embolism, a life-threatening
condition, also in the 15-30-day time interval. Overall, for these ninethrombotic symptoms, a random sampling from the year 2021 would
yield a COVID vaccine as opposed to any other vaccine 98.7% of theCovid-19 Vaccines

Covid-19
Vaccines

Table 4
Number of symptoms reported in VAERS, restricted to the US population, for theyear 2021, for various specific types of thrombosis, showing total counts for
COVID-19 vaccines and for all vaccines. Pulmonary embolism, a highly related
symptom, is also shown.

In this paper, we have identified both the heart and the liver as or­gans that can be expected to be affected by the mRNA vaccines. The
VAERS database shows a strong signal for both organs. Table 2 shows
the statistics for 2021 on major disorders of the heart, including
myocarditis, arrest (cardiac, cardiorespiratory and sinus arrest),
arrhythmia (including supraventricular, nodal, sinus, tachyarrhythmia
and ventricular arrhythmia), myocardial infarction (including acute andsilent), and cardiac failure (including acute, chronic and congestive).
Altogether, there were a total of 8,090 COVID-19 events related to theseheart conditions, representing nearly 98% of all the events for all thevaccines for these symptoms in 2021.
It is difficult to find all of the symptoms associated with liver damage
in VAERS, but we selected a number that had high enough counts to beof interest and that clearly represent serious liver problems. Altogether
there were 731 events in these categories for COVID-19 vaccines, as
shown in Table 3, representing over 97% of all the cases connecting
these conditions to any vaccine in 2021.

Symptom

Symptom

13

Symptom

Covid-19 Vaccines

All Vaccines

Percent COVID-19

Alzheimer’s dementia
Parkinsonian symptoms
Memory impairment
Anosmia
Mobility decreased
Cognitive disorder
TOTAL

37
83
1,681
3,657
8,975
779
15,212

39
89
1,720
3,677
9,743
815
16,083

94.9
93.3
97.7
99.5
92.1
92.1
94.6

S. Seneff et al.

Food and Chemical Toxicology 164 (2022) 113008

take decades to develop, and ordinarily one would assume that a vaccine
has nothing to do with it. While the numbers are small, most of the cases
in VAERS were linked to COVID-19 vaccines. Anosmia, also included in
the table on the vagus nerve, is especially interesting, because it is awell-known early sign of Parkinson’s disease, and it is also a wellidentified feature of SARS-CoV-2 infection. 99.5% of the cases withanosmia as a symptom were linked to COVID-19 vaccines. Overall, thesymptoms in this table were linked to COVID-19 vaccines nearly 95% of
the time.

Table 7
Number of symptoms reported in VAERS, restricted to the US population, for theyear 2021, for cancer of specific organs, showing total counts for COVID-19
vaccines and for all vaccines.

15.5. VAERS signal for cancer
Cancer is a disease generally understood to take months or, morecommonly, years to progress from an initial malignant transformation ina cell to development of a clinically recognized condition. Since VAERS
reports of adverse events are happening primarily within the first monthor even the first few days after vaccination (Rose, 2021), it seems likelythat the acceleration of cancer progression following vaccines would bea difficult signal to recognize. Furthermore, most people do not expect
cancer to be an adverse event that could be caused by a vaccine, andhence they fail to enter a report when cancer develops shortly after
vaccination. However, as we have outlined in our paper, if the mRNA
vaccinations are leading to widespread dysregulation of oncogene con­trols, cell cycle regulation, and apoptosis, then VAERS reports shouldreflect an increase in reports of cancer, relative to the other vaccines,
even if the numbers are small. The experiment demonstrating impair­ment of DNA repair mechanisms by SARS-CoV-2 spike protein in an invitro study provides compelling evidence that the vaccines could accel­
erate the rate of DNA mutations, increasing cancer risk (Jiang and Mei,
2021).
For our analysis of evidence of increased cancer risk in VAERS, we
focused on two somewhat distinct approaches. One, represented by the
results in Table 6, was to gather the counts for any terms that contained
keywords clearly linked to cancer, namely, “cancer,” “lymphoma,”“leukaemia,” “metastasis,” “carcinoma,” and “neoplasm.” Overall, we
found 1,474 entries linking these terms to COVID-19 vaccines, repre­
senting 96% of all the entries for any of these terms for any vaccine inthat year.
The complementary approach was to find terms involving cancer in
specific organs, namely, breasts, prostate, bladder, colon, brain, lungs,
pancreas and ovaries, as shown in Table 7. Although all the numbers are
small, the highest by far was for breast cancer (246 cases), with nearlyfour times as many hits as for lung cancer, the second most common
type. All of the cases for pancreatic, ovarian and bladder cancer werelinked to COVID-19 vaccines, with zero cases for any other vaccine.
Altogether, we tabulated 534 cases of cancer of specific organs linked to
COVID-19 vaccines, representing 97.3% of all the cases for any vaccine
in 2021.

Counts COVID-19
vaccines

Counts All
Vaccines

Percent
COVID-19

CancerLymphoma
Leukaemia
Metastatic/
metastasis
Carcinoma
Neoplasm
TOTAL

396
144
155
175

403
153
161
179

98.3
94.1
96.3
97.8

176
428
1,474

187
452
1,535

94.1
94.7
96.0

Counts COVID-19
vaccines

Counts All
Vaccines

Percent COVID19

Breast cancer
Prostate cancer
Bladder cancer
Colon cancer
Brain neoplasm
Lung cancer
PancreaticcancerOvarian cancer
Total

246
50
30
40
53
64
24

254
52
30
41
55
66
24

96.8
96.2
100
97.6
96.4
97.0
100

27
534

27
549

100
97.3

16. Conclusions
There has been an unwavering message about the safety and efficacy
of mRNA vaccinations against SARS-CoV-2 from the public healthapparatus in the US and around the globe. The efficacy is increasingly indoubt, as shown in a recent letter to the Lancet Regional Health byGünter Kampf (2021b). Kampf provided data showing that the vacci­
nated are now as likely as the unvaccinated to spread disease. He
concluded: “It appears to be grossly negligent to ignore the vaccinatedpopulation as a possible and relevant source of transmission when
deciding about public health control measures.” Moreover, the in­adequacy of phase I, II, and III trials to evaluate mid-term and long-termside effects from mRNA genetic vaccines may have been misleading on
their suppressive impact on the innate immunity of the vaccinees.
In this paper, we call attention to three very important aspects of thesafety profile of these vaccinations. First is the extensively documented
subversion of innate immunity, primarily via suppression of IFN-α andits associated signaling cascade. This suppression will have a wide rangeof consequences, not the least of which include the reactivation of latentviral infections and the reduced ability to effectively combat future in­fections. Second is the dysregulation of the system for both preventing
and detecting genetically driven malignant transformation within cells
and the consequent potential for vaccination to promote those trans­
formations. Third, mRNA vaccination potentially disrupts intracellularcommunication carried out by exosomes, and induces cells taking up
spike glycoprotein mRNA to produce high levels of spike-glycoproteincarrying exosomes, with potentially serious inflammatory conse­
quences. Should any of these potentials be fully realized, the impact on
billions of people around the world could be enormous and could
contribute to both the short-term and long-term disease burden ourhealth care system faces.
Given the current rapidly expanding awareness of the multiple rolesof G4s in regulation of mRNA translation and clearance through stressgranules, the increase in pG4s due to enrichment of GC content as aconsequence of codon optimization has unknown but likely far-reachingconsequences. Specific analytical evaluation of the safety of these con­structs in vaccines is urgently needed, including mass spectrometry for
identification of cryptic expression and immunoprecipitation studies toevaluate the potential for disturbance of or interference with theessential activities of RNA and DNA binding proteins.
It is essential that further studies be conducted to determine theextent of the potential pathological consequences outlined in this paper.
It is not practical for these vaccinations to be considered part of a publichealth campaign without a detailed analysis of the human impact of thepotential collateral damage. VAERS and other monitoring systems
should be optimized to detect signals related to the health consequencesof mRNA vaccination we have outlined. We believe the upgraded VAERS
monitoring system described in the Harvard Pilgrim Health Care, Inc.
study, but unfortunately not supported by the CDC, would be a valuable
start in this regard (Lazarus et al., 2010).

Table 6
Number of symptoms reported in VAERS, restricted to the US population, for theyear 2021, for various cancer-related terms, showing total counts for COVID-19
vaccines and for all vaccines.
Symptom

Symptom

14

Food and Chemical Toxicology 164 (2022) 113008

S. Seneff et al.

In the end, billions of lives are potentially at risk, given the large
number of individuals injected with the SARS-CoV-2 mRNA vaccines
and the broad range of adverse outcomes we have described. We call on
the public health institutions to demonstrate, with evidence, why theissues discussed in this paper are not relevant to public health, or toacknowledge that they are and to act accordingly. Furthermore, we
encourage all individuals to make their own health care decisions withthis information as a contributing factor in those decisions.

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Author contributions
S.S., G.N and A.K. all contributed substantially to the writing of theoriginal draft. P.M. participated in the process of editorial revisions.
Funding
This research was funded in part by Quanta Computers, Inc., Taipei,
Taiwan, under the auspices of the Qmulus project.
Declaration of competing interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
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