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\begin{document}

\title{SARS CoV-2 adenovirus and RNA based vaccines potential autoimmune
complications: could we lower the chances?}



\author[1]{Mina Kelleni}%
\affil[1]{Affiliation not available}%


\vspace{-1em}



  
  \date{May 26, 2024}


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\begin{abstract}
This preprint has been published:
\url{https://juniperpublishers.com/ijoprs/IJOPRS.MS.ID.555658.php}~Nucleic
acid based - mRNA based and adenovirus vectored - vaccines, were first
ever or first commercially ever approved for the public, respectively.
However, these newly emergency approved types possess a potential risk
to induce auto-immune diseases e.g., thrombocytopenia, myocarditis and
immune induced thrombosis and thromboembolism that might be fatal and
could reason for some of the post vaccination sudden death reports.
Moreover, all SARS CoV-2 types of vaccines, depending on the spike
protein immunogenicity, especially the conventional inactivated ones
might increase the likelihood of COVID-19 severity upon re-infection
through antibody dependent enhancement which might reason for the
recently described abundance of hospital admissions within seven days of
vaccination and might also reason for some of the serious adverse
effects encountered with administration of convalescent plasma to
COVID-19 patients as well as they might share in development of some
lethal SARS CoV-2 variants. Importantly, we suggest that SARS CoV-2 mass
vaccination campaigns were the worst ever decision made and that making
these COVID-19 vaccines compulsory or administering them to children or
pregnant participants might be considered as a crime against humanity to
the extent that no prior companies- governmental agreements would ever
secure impunity. Finally, a full informed personalized risk benefit
ratio especially for some described high-risk groups must be secured
while suggesting that the subunit vaccines are the least hazardous ones.%
\end{abstract}%



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Two clinical trials of SARS CoV-2 adenovirus vector -based vaccines have
been temporarily halted due to autoimmune complications concerns in some
participants. Similarly, SARS CoV-2 RNA vaccines possess a theoretical
potential to elicit autoimmune complications. After their approval to
combat the current COVID-19 pandemic, nucleic acid-based vaccination,
whether DNA or RNA, is considered first of its kind to be used in
humans. Potential risks including development of autoimmune diseases
might only be documented when used on a large scale as the clinical
trials have involved only tens of thousands of participants. Thus, a
strict system for post marketing surveillance must be secured to report
any potential adverse effect and the techniques used in development of
these types of vaccines should focus on innovative methods to decrease
their potential autoimmunity. Importantly, smokers, obese and diabetic
participants are more liable groups to develop autoimmune diseases and
we recommend a personalized risk benefit ratio to be evaluated before
vaccination waiting for further safety data coming from post marketing
surveillance. Finally, quitting smoking, loss of overweight and control
of blood glucose levels might help to lower their probabilities in case
of the benefits exceeded the risks.



Short communication

SARS CoV-2 adenovirus vector and RNA based vaccines potential autoimmune
complications: A Reasonable Explanation for the Sudden Death Reports.

Mina T. Kelleni, MD, PhD

pharmacology Department, College of Medicine, Minia University, Egypt

{mina.kelleni@mu.edu.eg}; {drthabetpharm@yahoo.com}

Mobile: +201200382422

\url{https://orcid.org/0000-0001-6290-6025}

Key messages:

Adenovirus vector and RNA based SARS CoV-2 vaccines possess a potential
risk to induce auto-immune diseases.

Nucleic acid-based vaccination is considered first of its kind to be
used in humans after their approval in Russia and UK to combat COVID-19

Clinical trials involved only tens of thousands of participants and
potential autoimmune complications might be revealed only post
marketing.

Autoimmune myocarditis might be the reason for the cardiac arrest/sudden
death reports encountered during the clinical trials and post marketing
(I've updated the text after the report coming from Portugal, sent to
another journal and today we read about the report of the Florida
Physician who died of immune thrombocytopenia complications, I wish I
might have time soonest to update also the text here).

Smokers, obese and diabetic individuals are in general more liable to
develop auto-immune diseases and an individualized risk benefit ratio
should be considered before vaccination.

An advice to quit smoking, lose overweight and control of blood glucose
level might prove beneficial to lower the incidence of these potential
autoimmune complications.

Keywords: COVID-19, SARS CoV-2, adenovirus vector vaccines, mRNA
vaccines, autoimmune diseases.

Graphical abstract\selectlanguage{english}
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\textbf{Smokers, obese individuals and diabetic patients are considered
more vulnerable to develop autoimmune diseases which are also considered
as potential adverse effects of SARS CoV-2 adenovirus and RNA-based
vaccines.}

\textbf{Introduction}

COVID-19 vaccines are~considered of utmost importance to stem SARS CoV-2
current pandemic, with 48 candidates in clinical evaluation, including
seven adenovirus, five messenger RNA (mRNA) and one self-amplifying RNA
based vaccines encoding spike protein of SARS CoV-2 as declared by the
WHO on the 12\textsuperscript{th} of November 2020{[}1, 2{]}. However,
the unprecedent accelerated timelines to develop some of COVID-19
vaccines have necessitated a call for active pre and post-licensure
safety surveillance systems to properly investigate potential adverse
effects or toxicities {[}1, 3{]}. Importantly, two adenovirus
vector-based SARS CoV-2 vaccine global phase III clinical trials were
temporarily paused due to reports of serious adverse medical events of
autoimmune complications including multiple sclerosis and transverse
myelitis which were ultimately deemed to be unrelated to the SARS CoV-2
vaccine. However, lack of transparency concerns have been raised as the
involved companies declined the release of the thorough details of these
serious adverse events claiming privacy issues {[}4-7{]} and a sharp
criticism of the analysis of the results of one trial including a
serious dose mistake that involved thousands of patients has also been
raised{[}8{]}. Notably, adenovirus vector SARS CoV-2 vaccine has been
first commercially approved in humans in Russia and is undergoing a mass
vaccination program{[}9, 10{]}.

\textbf{RNA based vaccines potential hazards}

~On the other hand, RNA based vaccines, recently first approved in UK
for COVID-19 as a first ever approval for this novel type of vaccination
in a western country {[}11{]}, possess multiple theoretical and
manufacturing advantages over traditional subunit, live attenuated and
killed virus vaccines{[}12-14{]}. However, in practice the results of
two previous clinical trials using mRNA vaccines to prevent H10N8, H7N9
influenza viruses and rabies have been lower than what was expected when
compared to those of their preclinical studies{[}13{]}. Similarly,
though mRNA vaccines encoding HIV and CMV antigens elicited
antigen-specific CD4+ and CD8+ T cell immune responses; no reduction in
viral load was observed{[}12{]}.

Similar to adenovirus vector-based vaccines, potential risks of mRNA and
saRNA based vaccines also include risk of potential autoimmunity with
possible development of autoreactive antibodies of any non-native
nucleotides and delivery system components {[}13, 15, 16{]}. All SARS
CoV-2 adenovirus vector and RNA vaccines phase III clinical trials
involved only tens of thousands of patients and this risk cannot be
fully excluded until post marketing safety data prove their safety.
Notably, soon after its mRNA based SARS CoV-2 vaccine approval, the UK
Medicines and Healthcare products Regulatory Agency advised people with
a history of significant allergic reactions to medicines, food or
vaccines not to have the jab {[}17{]} and the identification of
individuals at an increased risk of autoimmune reactions before mRNA
vaccination was advised{[}13{]}. We would like to explore some groups of
individuals who are potentially more vulnerable to autoimmune diseases,
aiming to recommend a personalized risk benefit ratio to be considered
before a decision to be immunized by adenovirus and RNA based SARS CoV-2
vaccine until encouraging post marketing safety data are revealed for
all SARS CoV-2 types of vaccines.

\textbf{Who are the higher-risk groups, and could we lower their chances
to develop autoimmune diseases?}

The first higher-risk group are smokers; cigarette smoke has been
reported to lead to an enhanced risk of inflammatory and autoimmune
diseases{[}18{]}. Smokers are more likely to develop critical COVID-19
requiring mechanical ventilation {[}19{]} that might lead to a higher
mortality rate {[}20, 21{]}. Interestingly, alarms about the danger of
misreading non-significant or inconclusive frequentist results
containing several possible biases of a contradictory hypotheses have
been raised {[}22, 23{]}. {}

Two other important groups that might be closely monitored include obese
and diabetic individuals; obesity was suggested to be a major
environmental factor contributing to the onset and progression of
autoimmune diseases{[}24{]} and a concomitant autoimmune disease was
encountered as 1 in 4 of 179,248 people diagnosed with type 1
diabetes{[}25{]}. Notably, a meta-analysis has showed diabetes, but not
obesity, to be linked to a higher COVID-19 mortality{[}26{]}. However,
increasing risks of COVID-19 hospital death were noticed to be
associated with increasing levels of obesity (BMI \textgreater{}40 fully
adjusted HR 2.27, 95\% CI 1.99-2.58){[}27{]}.{}

Interestingly, quitting smoking at diagnosis was recently shown to
decrease the risk of death in cancer patients{[}28{]}, and quitting
smoking was suggested to alleviate its impact in patients with pneumonia
and other COVID-19 associated infections{[}21, 23, 29{]}, thus a
beneficial advice to quit smoking together with another to lose
overweight and to control the blood glucose levels might also help to
lower the chances of SARS CoV-2 adenovirus and RNA-based vaccine
potential autoimmunity in those individuals. Most importantly, we would
like to stress the utmost importance to remind the participants to
report all experienced adverse effects to a well-prepared post marketing
surveillance system. Further, the search to improve methods that help to
develop nucleic acid based vaccines with minimal autoimmune potential
risk should continue and until more reassuring post marketing safety
data are released, we recommend considering an individualized risk
benefit ratio especially for those higher risk groups of patients.

Conflict of interests

the author declares he has no conflict of interest

Funding/Financial disclosure

None

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~

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