Review Not peer-reviewed version
Concerns regarding Transfusions of Blood Products Derived from Genetic Vaccine Recipients and for Specific Measures
Jun Ueda * , Hideyuki Motohashi , Yuriko Hirai , Kenji Yamamoto , Yasufumi Murakami , Masanori Fukushima , Akinori Fujisawa *
Posted Date: 15 March 2024
doi: 10.20944/preprints202403.0881.v1
Keywords: COVID-19 vaccine; genetic vaccine; blood product; blood transfusion; spike protein; post-
vaccination syndrome; harm–benefit assessment; prion; spikeopathy; inspection standard; diagnostic
criteria
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Review
Concerns regarding Transfusions of Blood Products
Derived from Genetic Vaccine Recipients and
Proposals for Specific Measures
Jun Ueda 1,*, Hideyuki Motohashi 2, Yuriko Hirai 3, Kenji Yamamoto 4, Yasufumi Murakami 5,
Masanori Fukushima 6 and Akinori Fujisawa 7,*
1 Department of Advanced Medical Science, Asahikawa Medical University, Asahikawa 078-8510,
Hokkaido, Japan; junueda@asahikawa-med.ac.jp
2 Pre-Clinical Research Center, Tokyo Medical University Hospital, 6-7-1 Nishi-Shinjuku, Shinjuku-ku,
Tokyo 160-0023, Tokyo, Japan; moto@tokyo-med.ac.jp
3 MCL Corporation, Jimukino-Ueda bldg. 603, 21 Sakaimachi Gojo-Takakurakado, Shimogyo-Ku, Kyoto 600-
8191, Kyoto, Japan; hirai@mcl-corp.jp
4 Department of Cardiovascular Surgery, Center of Varicose Veins, Okamura Memorial Hospital, 293-1
Kakita Shimizu-cho, Sunto-gun, Shizuoka 411-0904, Japan; yamamoto@okamura.or.jp
5 Department of Biological Science and Technology, Faculty of Advanced Engineering, Tokyo University of
Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125-8585, Japan; yasufumi@rs.tus.ac.jp
6 Foundation of Learning Health Society Institute, Nagoya 450-0003, Aichi, Japan; mfukushima@imrd.jp
7 Kokoro Medical Corporation, Honbetsu Cardiovascular Medicine Clinic, Honbetsu 089-3314, Hokkaido,
Japan; fujisawa.peace@mac.com
* Correspondence: junueda@asahikawa-med.ac.jp (J.U.); fujisawa.peace@mac.com (A.F.);
Tel.: +81-166-68-2385 (J.U.); +81-156-22-8888 (A.F.)
Abstract: The coronavirus pandemic was declared by the World Health Organization (WHO) in
2020, and a global genetic vaccination program has been rapidly implemented as a fundamental
solution. However, many countries around the world have reported that so-called genetic vaccines,
such as those using modified mRNA encoding the spike protein and lipid nanoparticles as the drug
delivery system, have resulted in post-vaccination thrombosis and subsequent cardiovascular
damage, as well as a wide variety of diseases involving all organs and systems, including the
nervous system. In this article, based on these circumstances and the volume of evidence that has
recently come to light, we call the attention of medical professionals to the various risks associated
with blood transfusions using blood products derived from people who have suffered from long
COVID and from genetic vaccine recipients, including those who have received mRNA vaccines,
and we make proposals regarding specific tests, testing methods, and regulations to deal with these
risks. We expect that this proposal will serve as a basis for discussion on how to address post-
vaccination syndrome and its consequences following these genetic vaccination programs.
Keywords: COVID-19 vaccine; genetic vaccine; blood product; blood transfusion; spike protein;
post-vaccination syndrome; harm–benefit assessment; prion; spikeopathy; inspection standard;
diagnostic criteria
1. Introduction
On March 11, 2020, the coronavirus pandemic was declared by the Director-General of the World
Health Organization (WHO) [1], and countries actively implemented classical public health
measures, including quarantine, isolation, disinfection, and lockdowns. However, hopes for a vaccine
grew as the general consensus was that rapid herd immunity was the best solution to overcome the
pandemic. Since 2021, as a means to combat SARS-CoV-2 infection, several global pharmaceutical
companies including Pfizer-BioNTech, Moderna, and AstraZeneca have developed various genetic
vaccines that use the spike protein of the Wuhan strain of SARS-CoV-2 as an antigen, and rapid
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page2
vaccination has been promoted on a global scale [2,3]. During this period, virological studies of SARS-
CoV-2 have been intensively conducted, and the pathogenic mechanism of this virus has been
elucidated in detail [4,5]. In brief, the key pathogenic processes include the binding of the spike
protein of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) receptor on vascular
endothelial cells, allowing viral entry and amplification [6]; the triggering of red blood cell and
platelet aggregation by the spike protein [7–11]; and the formation of microthrombi [12,13].
However, it has been reported from various countries around the world that genetic vaccines
such as mRNA vaccines encoding spike proteins have also caused a wide variety of diseases in all
organs and systems, including the nervous system, in addition to thrombosis and resulting
cardiovascular disorders in vaccine recipients [14–21]. This is because when the foreign gene was
introduced into autologous cells using gene-transfer capable lipid nanoparticles (LNPs) or other
means, the spike proteins produced from the mRNA or DNA introduced via the gene vaccine
induced thrombosis in the vaccine recipient. While evidence for specific problems has been reported
individually, Parry et al. have proposed the theory of spikeopathy (spike disease) as a hypothesis
that synthesizes all of the evidence for this problem [22]. Furthermore, there are two general
mechanisms by which a modified gene introduced into the body by genetic vaccination and some of
the antigens produced because of the expression of that gene can be transmitted throughout the body.
First, LNPs encapsulating mRNA can spread through the body via the bloodstream from the injection
site. It has already been shown that LNPs have a tendency to accumulate in specific organs, such as
the liver, spleen, ovaries, testes, and bone marrow [22,23]. The other is the release of
pseudouridinated mRNA molecules and synthesized spike proteins as extracellular vesicles, or
exosomes, from cells that have incorporated LNPs. These exosomes are transported in the circulation
throughout the body to reach various organs [24–27]. And it has already been proven that spike
proteins produced by cells that have taken up the modified gene travel throughout the body in the
bloodstream [28,29]. Thus, it must be emphasized that the transport, distribution, and expression of
the components of the genetic vaccine beyond the administration site to organs and tissues of the
whole body after vaccination involve the risk of inducing various conditions.
Although the Director-General of the WHO declared the end of the COVID-19 public health
emergency on May 5, 2023, post-vaccination syndrome (PVS), caused by genetic vaccines that have
been promoted worldwide and have been given to billions of people, has become a major global
problem [19,21,27,30] requiring a reasonable harm–benefit assessment of the global use of genetic
vaccines [27,31–33]. Since the beginning of the coronavirus pandemic and genetic vaccination, there
has been much debate about the safety of blood products and their use in transfusions [34–39].
However, because the pathology of SARS-CoV-2 was not fully understood at the beginning, there
was no specific discussion based on data or analysis of what was a problem and what could be a risk;
only concerns were expressed, and no clear conclusions or policies were drawn. For example, Jacobs
et al. argued that there was no requirement to collect or share the genetic vaccination status of blood
donors and that hospitals were not required to inform patients about the genetic vaccination status
of blood donors [37], because there were no reports of health issues from genetic vaccination in 2021.
However, this argument was not based on data. Contrary to initial expectations, it was found that
genes and proteins from genetic vaccines persist in the blood of vaccine recipients for prolonged
periods of time [22,28,40–44], and a variety of adverse events resulting from genetic vaccines are now
being reported worldwide. Roubinian et al. reported that transfusions of plasma and platelet blood
components collected before and after COVID-19 vaccination were not associated with increased
adverse outcomes in transfusion recipients who did not develop COVID-19 [39]. However, they
evaluated only plasma and platelet preparations, not red blood cell or whole blood preparations. The
long-term effects remain unclear, as the study only followed up recipients to the point of 30-day
readmission rates.
Considering the current situation and the volume of evidence that has recently come to light,
the purpose of this article is to raise awareness among relevant parties and point toward future
directions by making specific recommendations regarding the use of blood products derived from
genetic vaccine recipients, including those who have received mRNA vaccines. To be more precise,
genetic vaccines are the equivalent of biomedicine (i.e. immune therapeutics) rather than
conventional vaccines in terms of their mechanism of action [45,46]. The various genetic vaccines now
treated as vaccines should originally have been treated as biomedicine, but because they were
classified as vaccines, huge numbers of people were inoculated with them [2,3]. As a result, extensive
areas of medicine are now beginning to be affected because most of the population in many countries
has been vaccinated [19,21,27,30,47]. This has never happened before in the history of biomedicine,
and consequently, it is highly suspected that blood products for transfusion have been affected by
these so-called genetic vaccines. Therefore, this review was prepared to examine the risks of blood
transfusions at the current stage when genetic vaccines are administered in large quantities. The
vaccine recipients described in this proposal are limited to genetic vaccine recipients.
2. Overview of Cases of Blood Abnormalities after Genetic Vaccination
A wide variety of diseases related to blood and blood vessels, such as thrombosis, have
developed after genetic vaccination, including with mRNA vaccines, and many cases of serious
health injuries have been reported. For example, a PubMed search on diseases such as
thrombocytopenia, thrombotic disorders with thrombocytopenia, deep vein thrombosis,
thrombocytopenic purpura, cutaneous vasculitis, and sinus thrombosis combined with the essential
keywords “COVID-19 vaccine” and “side effects” yielded several hundred articles in only about two
years since the rollout of genetic vaccines [14,17,20,21,48]. In addition to abnormally shaped red blood
cells, amorphous material has been found floating in the blood of mRNA-vaccinated individuals
under microscopic observation, some of which has shown grossly abnormal findings (Table 1, point
5) [7–10,49]. Recent studies have also reported that the spike protein has amyloidogenic potential [50–
54], is neurotoxic [55–57], and can cross the blood–brain barrier [58–60]. Thus, there is no longer any
doubt that the spike protein used as an antigen in genetic vaccines is itself toxic [22,61,62].
In addition to thrombosis, individuals who have received multiple doses of a genetic vaccine
may have multiple exposures to the same antigen within a brief period, thereby being imprinted with
a preferential immune response to that antigen [63,64]. This phenomenon, called original antigenic
sin or immune imprinting, has caused COVID-19 vaccine recipients to become more susceptible to
contracting COVID-19 [65].
In addition, antibody-dependent enhancement of infection is also known;
antibodies produced by vaccination may rather promote viral infection and symptoms [66,67]. On
the other hand, it has also been suggested that repeated administration of genetic vaccines may result
in immune tolerance because of a class switch to non-inflammatory immunoglobulin G4 (IgG4) [68–
71], whereby the immune system of the recipient does not mount an excessive response such as
cytokine storm [27,72], and case reports of IgG4-related disease have begun to appear [73–75]. This
raises concern that alterations in immune function due to immune imprinting and immunoglobulin
class switching to IgG4 may also occur in genetic vaccine recipients. This may increase the risk of
serious illness due to opportunistic infections or pathogenic viruses that would not normally be a
problem if the immune system were normal [76–82]. For example, cases of suspected viremia have
been reported [82]. Therefore, from the perspective of traditional containment of infectious diseases,
greater caution is required in the collection of blood from genetic vaccine recipients and the
subsequent handling of blood products, as well as during solid organ transplantation and even
surgical procedures [83–87] in order to avoid the risk of accidental blood-borne infection (Table 1,
point 3) [84–87]. The phenomenon of immune imprinting can occur even when spike protein is not
used as an antigen or when another antigen is used (e.g. inactivated influenza vaccine) [88]. However,
compared to conventional inactivated vaccines, genetic vaccines, which produce an antigen within
the body, are expected to prolong the period of exposure to the same antigen, and as a result, the risk
of immune imprinting may be higher than with conventional vaccines. It is not actually known how
long the vaccine components remain in the body after a person has received a genetic vaccine
[22,40,43], but it is expected that they will remain in the body for a longer period than originally
thought, in part because spike protein has been detected in the bodies of people several months after
vaccination (Table 1, point 1) [22,28,41,42]. In addition, since long-term exposure to a specific identical
antigen (in this case, spike protein) causes immunoglobulins to become IgG4 [68,70] and some of thepage4
B cells that produce them are likely to differentiate into memory B cells that survive in the body for
a sustained period [70,89], the immune dysfunction of genetic vaccine recipients is expected to be
prolonged (Table 1, point 3 & 6). More details on these points are expected to be revealed in the future.
In summary, there is an undeniable risk that patients may experience some problems if they
receive blood products derived from blood collected in, at least, a brief deferral period after genetic
vaccination. Although it is unknown at present whether secondary damage is caused by transfusion
of blood products derived from genetic vaccine recipients, it is necessary for medical institutions and
administrative organizations to respond and investigate cooperatively, keeping various possibilities
in mind, because mechanisms such as the toxicity of the spike protein itself and the effects of LNPs
and modified mRNA on the immune response have not been fully elucidated and are still under
study. It should be emphasized that a significant proportion of the COVID-19 PVS in mRNA vaccine
recipients is due to toxic spike proteins, and the inclusion of structures in the receptor-binding
domain within these proteins that may induce prion disease is particularly alarming, as Seneff et al.
and Perez et al. have warned [50,90–96]. Furthermore, it has been shown that prion similarity in the
receptor-binding domain exists not only in the spike protein of the Wuhan strain, which is still used
as an antigen in genetic vaccines, but also in the spike protein of variants of SARS-CoV-2, such as the
Delta strain, with the exception of the Omicron strain [93,97]. Whether we should be uniformly
vigilant for the spike protein of the coronavirus or just the spike protein of certain variants, such as
the Wuhan strain, awaits further analysis.
Table 1. Major concerns with the use of blood products derived from gene vaccine recipients.
Concerns Description References
1 Spike protein contamination
The spike protein, which is the antigen of SARS-CoV-2 and genetic vaccines,
has already been found to have various toxicities, including effects on red
blood cells and platelet aggregation, amyloid formation, and neurotoxicity.
It is essential to recognize that the spike protein itself is toxic to humans. It
has also been reported that the spike protein can cross the blood–brain
barrier. Therefore, it is essential to remove the spike protein derived from
the gene vaccine itself from blood products.
[22,29,55–
60]
2
Contamination with amyloid
aggregates and microthrombi
formed by spike proteins
It is not yet clear how the amyloid aggregates and microthrombi formed by
the spike proteins develop into visible thrombi. However, once formed,
amyloid aggregates may not be readily cleared and therefore need to be
removed from blood products. These amyloid aggregates have also been
shown to be toxic.
[51,52,98]
3
Events attributable to
decreased donor immune
system and immune
abnormalities due to immune
imprinting or class switch to
IgG4, etc. resulting from
multiple doses of genetic
vaccines
When the immune function of a donor is impaired by gene vaccination,
there is a risk that the donor has some (subclinical) infectious disease or is
infected with a pathogenic virus and has developed viremia or other
conditions, even if the donor has no subjective symptoms. For this reason,
healthcare professionals who perform surgical procedures, including blood
sampling and organ transplantation, as well as using blood products,
should manage the blood of genetic vaccine recipients with care to prevent
infection through blood. It will also be necessary to inform all healthcare
professionals of these risks. [63–65,68–71,76–80,82–87]
4
Lipid nanoparticles (LNPs) and
pseudouridinated mRNA
(mRNA vaccines only)
In the case of mRNA vaccines, LNPs and pseudouridinated mRNA may
remain in the blood of recipients if blood is collected without a sufficient
deferral period after gene vaccination. LNPs are highly inflammatory and
have been found to be thrombogenic themselves, posing a risk to
transfusion recipients. LNPs itself has potent adjuvant activity and is at risk
of inducing Adjuvant-Induced Autoimmune Syndrome (ASIA syndrome).
An additional risk is that if the pseudouridinated mRNA is incorporated
into the recipient’s blood while still packaged in LNPs, additional spike
protein may be produced in the recipient’s body.
[23,40,44,99–
105]
5
Contamination with
aggregated red blood cells or
platelets
The spike protein causes red blood cells and platelets to aggregate and
therefore these aggregates will be carried into the recipient’s blood unless
they are removed from the blood product.
[7–11,49]
6
Memory B cells producing IgG4 and IgG4 produced from them
Large amounts (serum concentration typically above 1.25–1.4 g/L) of non-
inflammatory IgG4-positive plasma cells can cause chronic inflammation
such as fibroinflammatory disease. [73–75,106,107]
3. Specific Proposals for Blood Sampling and Blood Products from Vaccine Recipients
In the previous section, we discussed a variety of blood-related abnormalities that have occurred
following genetic vaccination. In this section, we provide specific proposals on how to respond to
these circumstances. Because blood contamination affects so many areas of health care, it is especially
important to anticipate the worst [95,96,108–110] and to plan and act from the start to ensure that
there are no lapses or omissions.
3.1. Additional Requirements for Blood Collection (Donation)
Currently, in Japan, the Japanese Red Cross Society (https://www.jrc.or.jp/english/) plays a
central role in blood collection activities, and its blood products are used for blood transfusions and
other purposes. The Japanese Red Cross Society has a rule that blood can be collected from genetic
vaccine recipients after a deferral period (48 hours for mRNA vaccine recipients and 6 weeks for
AstraZeneca DNA vaccine recipients), but the data and rationale for the rule have not been specified.
As with infections such as human immunodeficiency virus (HIV) and prion diseases, a history of
genetic vaccination (DNA and/or mRNA type), including timing and number of doses, should be
obtained by interview, and kept in the official record when blood is collected (Figure 1, Table 2).
Additional caution is needed, particularly if not many days have passed since the genetic vaccine
was administered, because LNPs [23,101–103] and spike protein mRNA, which can induce
inflammation, may remain in the blood (Table 1, point 4) [22,40,43,44]. If certain events such as
anaphylactic shock occur immediately after genetic vaccination, the effects of LNPs should also be
suspected [100]. It has also been reported that negatively charged LNPs themselves interact with
fibrinogen to form thrombi [99]. Therefore, the presence of LNPs may itself be a factor in the need for
caution with transfusion products.
On the other hand, even if a person has not received a genetic vaccine, if they have had long
COVID, it is possible that the spike protein remains in their body, and thus it would be better to keep
an official record of whether they have long COVID or not [51,111–113]. As the degradation rates of
pseudouridinated mRNA and spike protein in the body are unknown at present, blood products
derived from genetic vaccine recipients should be used with extreme caution, being conscious of the
cases of AIDS, bovine spongiform encephalopathy (BSE), and variant Creutzfeldt-Jakob disease
(vCJD) caused by the use of contaminated blood products in the past [110,114–121]
page6
Figure 1. Summary of items and procedures required for management of blood products derived
from gene vaccine recipients or contaminated with spike protein and modified genes. As with any
risk management exercise, it is important to constantly revise policies and procedures as risks and
problems are identified. PVS, post-vaccination syndrome.
Table 2. Tests needed to confirm the safety of blood products.
Concerns Description References
1 Spike protein content in blood
Immunochemical techniques include enzyme-linked immunosorbent assay,
immunophenotyping, mass spectrometry, liquid biopsy, and a combination
of liquid biopsy and proteomics. First, we propose mass spectrometry that
can directly measure the protein itself.[28,29,122–126]
2 Spike protein mRNA PCR and/or liquid biopsy are the options. If mRNA for the spike protein is
detected, LNPs may be present (mRNA vaccines only).[124,127,128]
3 Spike protein DNA
PCR and liquid biopsy are the options. This test is necessary because AstraZeneca’s viral vector is a DNA vaccine. For mRNA vaccines, it is believed that pseudouridinated mRNA is not reverse transcribed, but this
test is required if the spike protein remains for a prolonged period. [124,128]
4 Markers associated with autoimmune disorders
Long-term persistence of the spike protein in the blood increases the risk of
autoimmune disease. Therefore, it would be useful to test for autoimmune
disease using antinuclear antibodies as biomarkers in people who are
positive for the spike protein, taking into account the results of interviews
regarding the subjective symptoms. [27,105,129,130]
5 Interview
A history of genetic vaccination and COVID-19, current and previous medical history, and subjective symptoms (e.g. headache, chest pain, shortness of breath, malaise) should be obtained from blood donors and formally recorded. The types of questions included in the interview are critical to facilitate diagnosis and treatment of COVID-19 PVS, as more people are complaining of psychiatric and neurological symptoms after genetic vaccination.[15,131,132]
page 7
6Proteins resulting from frameshifting of pseudouridinated mRNA
Although it is not yet clear whether proteins other than the spike protein
are translated from pseudouridinated mRNAs, mass spectrometry may be
useful in confirming this.
[133]
7 Components of amyloid aggregates and thrombi
Common markers of thrombosis, such as D-dimer, are used first. Once the
major components of amyloid aggregates and thrombi have been identified,
their use as biomarkers is proposed. Understanding the composition of
amyloid aggregates will be important in the future, as amyloid aggregates
have been reported to be toxic. Understanding the composition of amyloid
aggregates may provide clues to how amyloid is broken down.
[51,52,98,134
]
8
Components of SARS-CoV-2
other than the spike protein
gene
This test will help determine whether the spike protein is from the genetic
vaccine or from SARS-CoV-2. Potential candidates include nucleocapsid. [4,5,41,128]
9 Immunoglobulin subclasses
It may be necessary to analyze immunoglobulin subclasses (the amount of
IgG4) if immunosuppression from multiple doses of the genetic vaccine is a
concern.[68–71]
10 Anti-nucleocapsid antibodies
The presence or absence and amount of anti-nucleocapsid antibodies as well
as antibody isotypes may be an indicator(s) in distinguishing whether
genetic vaccination or long COVID is the cause. [135–137]
11 Other
Myocarditis and pericarditis after genetic vaccination have been reported in various countries. Therefore, those with subjective symptoms may also be tested for myocarditis marker, such as cardiac troponin T. [18,19,29,138–140]
3.2. Handling of Existing Blood Products
At present, the genetic vaccination status of blood donors is not confirmed or controlled by
organizations including medical institutions, and the use of blood collected from these donors for
transfusions may pose risks to patients. Therefore, when blood products derived from gene vaccine
recipients are used, it is necessary to confirm the presence or absence of spike protein or modified
mRNA as in other tests for pathogens (Figure 1, Table 2). These should be quantified by an
immunochemical enzyme-linked immunosorbent assay (ELISA), by immunophenotyping, by direct
mass spectrometry of the protein itself, by an exosome-based liquid biopsy as used in cancer
screening, or by PCR [28,29,122–128]. For protein assays, as it may take time to generate a good-
quality anti-spike protein antibody or a positive control for a recombinant spike protein to be
compared with, and to sort and distribute them to each laboratory, we suggest that mass
spectrometry be used as an initial step to identify and quantify the spike protein itself in blood
[28,125]. In parallel with this, an analysis of the components of the spike protein-induced amyloid
material will be needed [51,98]. Once the components of amyloid aggregates are identified, they can
be used as biomarkers in the future. Exosome analysis will also be useful as a test as it has already
been shown that spike proteins and their genes are transported in the circulation around the body by
exosomes [24–27].
If the blood product is found to contain the spike protein or a modified gene derived from the
genetic vaccine, it is essential to remove them. However, there is currently no reliable way to do so.
As noted above, the prion-like structure within the spike protein molecule [91,95,96] suggests that
this molecule may be a persistent, sparingly soluble, heat-resistant, and radiation-resistant protein
[141,142]. The prion protein can be inactivated by thiocyanate, hydroxide, and hypochlorite [143–
145], but it is not yet known whether these can be applied to the spike protein and the resulting
amyloid materials. Therefore, as there is no way to reliably remove the pathogenic protein or mRNA,
we suggest that all such blood products be discarded until a definitive solution is found. Discarding
blood products prepared from blood collected from many dedicated blood donors can be very
painful, but it is necessary because the spike protein itself has been shown to induce thrombosis and
similar diseases. However, some medical facilities may have difficulty disposing of blood products
immediately, in which case it is essential to add the possibility of contamination with spike protein
or other foreign substances to the transfusion consent form and to fully explain this to the patient. In
any case, to prevent and reduce medical accidents caused by contaminated blood, it is imperative to
underscore the importance of confirming the history and frequency of genetic vaccination at the time
of blood collection and this information should be documented as an official record, managed and
stored by both medical and governmental organizations (see Figure 1, Table 2)fe.
page 8
3.3. The Need for Regular Checkups and Cohort Studies to Gain a Complete Picture of Blood Contamination
As the residual status of spike protein or modified gene fragments derived from genetic vaccines
is currently unknown, it will be necessary in the future to include measurement of these amounts in
routine health checkups. It is also necessary to include a section in the routine medical checkup
questionnaire to check genetic vaccination status and the number of vaccinations to obtain an overall
picture of the residual status of spike proteins in the blood. This is because a variety of conditions
following genetic vaccination involve thrombosis and immunological conditions [12,14,16,17,21,22,68,70]. Therefore, abnormalities in blood components related to these events shouldalso be analyzed.
On the other hand, when exosomes collected from vaccine recipients were administered to mice
that had not been vaccinated with the genetic vaccine, the spike protein was transmitted [25].
Therefore, it cannot be denied that the spike protein and its modified genes can be transmitted
through exosomes. For this reason, we suggest that full testing be done initially, regardless of genetic
vaccination status, and that a cohort study be conducted to quickly capture the full picture (Figure
1). This is a steady, labor-intensive effort that requires collaboration between all parties involved, but
such analyses may lead to the development of diagnostic criteria and testing for COVID-19 PVS. In
addition, as mentioned above, it cannot be ruled out that even those who have not been vaccinated
with the genetic vaccine, but have had long COVID, may have residual spike proteins or fibrin-
derived microthrombi in their bodies, so it would be advisable to conduct the same testing and
follow-up as for genetic vaccine recipients [51,52,111–113]. The presence or absence and amount of
anti-nucleocapsid antibodies as well as antibody isotypes may be an indicator(s) in distinguishing
whether genetic vaccination or long COVID is the cause (Table 2, point 10) [135–137]. In any case,
these cohort studies are expected to help establish cutoff values for blood levels of spike protein and
other substances to determine the safety of blood products. Faksova et al. conducted a large cohort
study of 99 million people using a multinational Global Vaccine Data Network™ (GVDN ®) and found
a significantly increased risk of myocarditis, pericarditis, Guillain-Barre syndrome, and cerebral
venous sinus thrombosis in genetic vaccine recipients [140]. This type of study will be increasingly
necessary in the future.
3.4. The Need for Early Development of Clinical Practice Guidelines and Diagnostic Criteria for COVID-19
PVS
Although the spectrum of COVID-19 PVS is diverse, it is characterized by a high prevalence of
hematologic and immune-related diseases [21]. Considering this, regardless of the transfusion issues
discussed in this review, blood tests are likely to be the first step in the diagnosis of COVID-19 PVS.
The ability to rapidly develop highly accurate testing systems, particularly blood tests, in
collaboration with other countries will be critical in treating patients suffering from PVS due to the
COVID-19 vaccine. Additional meta-analysis of data from systematic reviews and cohort analyses
will be needed to prevent bias in diagnostic criteria and to develop appropriate clinical practice
guidelines (Figure 1) [146–148].
4. Problems following Blood Transfusion Using Blood Products Prepared from Donated Blood
of Genetic Vaccine Recipients and the Need for Traceability of Blood Products for Transfusion
With the advent of genetic vaccination, there has been considerable debate about the safety of
blood products prepared from donated blood of the vaccine recipients and their use in blood
transfusion [36–39]. However, what happens in the body when a genetic vaccine such as an mRNA
vaccine is administered in the first place is not well understood at this stage, and as mentioned above,
the results of tests on the vaccine recipient’s blood need to be evaluated. Cases of encephalitis caused
by blood from dengue vaccine recipients have been reported as recently as 2023 [149], indicating that
the current system for managing and tracking blood products is not adequate. Unless accurate tests
are established, no conclusions can be drawn about the risk or safety of blood transfusions using
blood products from gene vaccine recipients. Thorough and continuous investigation is therefore9
necessary. To accomplish this, all potential donors should be registered, traceability of blood
products should be ensured, and rigorous recipient outcome studies and meta-analysis should be
maintained. Furthermore, as we have repeatedly stated, it is essential to rigorously obtain from
donors a history of vaccination and COVID-19 infection, preserve official records, and store samples
of blood products for later detection and verification of substances such as spike proteins and
exosomes (Figure 1). Given the wide variety of tests and records, the movement of people around the
world, and the import/export of blood products, it may be necessary in the future to establish
traceability by introducing blockchain technology into the management of blood products while
maintaining anonymity [150,151].
5. The Need for the Development of Relevant Legislation
The issue of blood products derived from genetic vaccine recipients described in this review is
expected to affect a very wide range of areas in countries around the world. In Japan, the “Act on
Prevention of Infectious Diseases and Medical Care for Patients with Infectious Diseases”
(https://www.japaneselawtranslation.go.jp/en/laws/view/2830/en) has been enacted to prevent the
spread of infectious diseases through blood products, and the “Act on Organ Transplantation” has
been enacted to handle organ transplants. The Ministry of Health, Labour and Welfare (MHLW) has
issued the “Guidelines for Blood Transfusion Therapy” regarding blood transfusions. These laws and
guidelines specify the responsibilities of the public, physicians, and national and local governments
and protect their rights. However, as the spike protein used as an antigen or its gene is not an
organism, there are likely to be number of difficult issues, such as how to legally define its
pathogenicity. From this point of view, when the risks of and health injuries caused by blood
products derived from genetic vaccination recipients have been roughly clarified (Table 2), it will be
essential to formulate regulations to reduce and prevent risks and contamination, by developing
related laws with the participation of the legislative branch, legal experts, medical administration
personnel, healthcare providers, and medical researchers, and by taking measures such as checking
vaccination status and dates, and legally regulating the import/export of blood products (Figure 1).
The wide range of issues makes coordination between agencies and healthcare professionals essential
from the outset.
Second, it is expected that the situation will already be complicated because, in contrast to
previous drug disasters, genetic vaccination was implemented on a global scale and simultaneously
for a substantial number of people [2,3]. This means, as in the context of the coronavirus pandemic,
or even more critically, that there is an urgent necessity for legislation and international treaties
explicitly elucidating bilateral and multilateral agreements concerning the management of blood
products. These legal frameworks should delineate regulations governing the handling of blood
products and establish protocols for governmental compensation and response to issues and hazards
associated with these products, including penalties and prohibitions. For example, the International
Health Regulations (IHR) 2005 may be helpful [152,153], but given the WHO’s strong push for genetic
vaccination [154], another framework may be needed. In relation to the cohort studies described in
Section 3.3 of this article, it will also be necessary for countries to conduct active epidemiological
surveys [155], as was the case with COVID-19, to compile the results of these surveys, and to establish
an international organization tasked with monitoring response efforts and assessing damages within
each country (Figure 2). It is expected that it will be important to incorporate not only the perspective
of infectious diseases but also biosafety and biosecurity [153,156].
As for Japan, Article 15 (2) of the Infectious Disease Act
(https://www.japaneselawtranslation.go.jp/ja/laws/view/2830/en#je_ch3at5) stipulates that the
Japanese government is responsible for conducting epidemiological studies. Given the significant
health risks associated with COVID-19 PVS, we urge the Japanese government to prioritize the
analysis and safety verification of blood products derived from gene vaccine recipients. This is
imperative given the urgent nature of the situation.
age 10
Figure 2. An example of a system for managing health injuries among genetic vaccine recipients.
Given the global nature of genetic vaccination and the movement of vaccine recipients and blood
products between countries, there will be a need for an international surveillance network to
coordinate countries.
6. Other Important Considerations
There is an urgent need to develop methods to identify as well as remove spike proteins and
modified genes derived from gene vaccines in blood products. In order to develop a uniform
inspection standard, there is an urgent need in Japan for the Japanese Society of Hematology
(http://www.jshem.or.jp/modules/en/index.php?content_id=1), the Japanese Society of Transfusion
and Cell Therapy (http://yuketsu.jstmct.or.jp/en/), and their related organizations to develop
guidelines on how to handle blood products that contain residual spike proteins or their modified
genes. Also, as noted earlier, gene vaccination has been promoted on a global scale [2,3], which will
necessitate coordination and exchange of information with national administrations and relevant
international medical societies (Figure 1). International guidelines on the handling of blood products
and the establishment of an international investigatory organization will be necessary (Figure 2).
However, there is an urgent need to share the risks of transfusion of blood products derived from
genetic vaccine recipients among the parties concerned, and prompt investigation and response by
all parties concerned is essential. The most important initial action is to make the relevant medical
personnel aware of this situation.
In the development of various guidelines, it will be helpful to refer to the response of each
country when the transmission of BSE and vCJD, also through blood transfusion, became a problem
(e.g. the Creutzfeldt-Jakob Disease International Surveillance Network in
page 11
https://www.eurocjd.ed.ac.uk/) [110,114,115,121,157]. For example, in the United Kingdom, when
BSE became a social problem and the mode of transmission of prion protein was unknown,
leukodepletion of blood products was conducted universally. Whether this was effective in
preventing transmission of BSE and vCJD through blood products is controversial [110,120,121,158],
but it was not common at the time to remove white blood cells from all blood products, as is now
routinely done with collected blood. However, because of leukodepletion, the safety of blood
products has increased [159]. In the case of the spike protein, which causes abnormalities such as
agglutination of red blood cells and platelets [8–11,49], we do not expect the problem to be eliminated
by leukodepletion alone. However, it is worth confirming whether washing of red blood cells can be
effective [160,161]. In urgent cases, autotransfusion may be an option [162].
Recent studies have shown that RNA pseudouridylation can result in frameshifting [133]. It is
not yet clear whether a portion of the pseudouridinated mRNA for the spike protein is translated into
another protein of unknown function in vaccine recipients. If these proteins are also pathogenic,
additional testing for such frameshift proteins may be needed in the future. Even if a frameshift
protein is not toxic, it must be foreign to the body and could cause autoimmune disease. In addition,
LNPs themselves are highly inflammatory substances [23,100–102], as described in Section 3.1, but
LNPs have been found to have stronger adjuvant activity than the adjuvants used in conventional
vaccines [104], and there is also concern about autoimmune diseases resulting from this aspect (Table
1, point 4) [105,163]. Thus, although it is not clear what the causative agent of autoimmune disease
is, the large number of reported cases of autoimmune disease following genetic vaccination is
extremely concerning [15,21,27,30,105,164]. The very mechanism of gene vaccines that causes one’s
own cells to produce the antigens of pathogens carries the risk of inducing autoimmune diseases,
which cannot be completely avoided even if mRNA pseudouridylation technology is used. In this
context, individuals with a positive blood test for spike protein may need to have interviews and
additional tests for autoimmune disease indicators, such as antinuclear antibodies (Table 2, point 4)
[27,105,129,130]. Alternatively, if the amino acid sequence of the protein resulting from the frameshift
is predictable, these candidate proteins could be included in the initial mass spectrometry assay
(Table 2, point 6). In any case, it is particularly important to develop tests and establish medical care
settings in anticipation of these situations.
7. Conclusion
Finally, we would like to state that if we continue to use genetic vaccines such as
pseudouridinated mRNAs and mRNA-LNP platforms [46,103], there will be further risks like those
described in this review. It should also be stressed that the issues discussed here are matters that
pertain to all organ transplants, including bone marrow transplants, and not just blood products. The
impact of these genetic vaccines on blood products and the actual damage caused by them are
unknown at present. Therefore, in order to avoid these risks and prevent further expansion of blood
contamination and complication of the situation, we strongly request that the vaccination campaign
using genetic vaccines be suspended and that a harm–benefit assessment be carried out as early as
possible, as called for by Fraiman et al. and Polykretis et al. [27,31–33]. As we have repeatedly stated,
the health injuries caused by genetic vaccination are already extremely serious, and it is high time
that countries and relevant organizations take concrete steps together to identify the risks and to
control and resolve them.
Author Contributions: Conceptualization, J.U. M.F. and A.F.; investigation, J.U. H.M. Y.M. M.F. and A.F.;
resources, Y.H.; data curation, J.U. H.M. M.F. and A.F.; writing—original draft preparation, J.U.; writing—
review and editing, J.U. H.M. Y.H. K.Y. M.F. and A.F.; visualization, J.U.; supervision, J.U. M.F. and A.F.; project
administration, J.U. M.F. and A.F.; funding acquisition, M.F. and A.F. All authors have read and agreed to the
published version of the manuscript.
Funding: The study was supported by donations from members of the Japanese Society for Vaccine-related
Complications and the Volunteer Medical Association.
Institutional Review Board Statement: Not applicable.
Acknowledgments: We would like to express our deep appreciation to the members of the Volunteer Medical Association for their help in the discussions that led to the preparation of this review.
Conflicts of Interest: The authors declare no conflict of interest in connection with this research.
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