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Cytokine Storm Response to COVID-19 Vaccinations

Cytokine Storm Response to COVID-19 Vaccinations
Esmaeil Farshi *
Peace and Health Organization, San Diego, California, USA
*Corresponding author: Esmaeil Farshi, Peace and Health Organization, San Diego, California, USA; E-mail:
Received: December 01, 2020; Accepted: December 15, 2020; Published: December 22, 2020
Copyright: © 2020 Farshi E. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original author and source are credited.
Vaccination against SARS-Cov-2 may lead to Cytokine Storm
Syndrome in some vaccinated people. We tested vaccination in 33
monkeys and 200 mice and we found vaccinated animals were able to
fight off the virus well with resulting a quickly clearing the virus from
their lungs except two monkeys and 9 mice. Those two monkeys along
9 mice showed syndrome of cytokine storm in their lungs. This result
is extremely important for human vaccination.
The term “cytokine storm” actually recalls the role of the immune
system in producing an uncontrolled and generalized inflammatory
response [1]. The term cytokine storm was first used in describing the
events modulating the onset of the graft-versus-host disease, a
condition characterized by an impressively strong activation of the
immune system [2]. Taken together, these data clearly indicate that, in
SARS-CoV-2 infection, Acute respiratory distress syndrome (ARDS)
is the ultimate result of a cytokine storm. In this scenario, the release
by immune effector cells of large amounts of pro-inflammatory
cytokines (IFNα, IFNγ, IL-1β, IL-6, IL-12, IL-18, IL-33, TNFα,
TGFβ) and chemokines (CXCL10, CXCL8, CXCL9, CCL2, CCL3,
CCL5) precipitates and sustains the aberrant systemic inflammatory
response [3]. The cytokine storm is readily followed by the immune
system “attacking” the body, which in turn will cause ARDS and
multiple organ failure, the final result being death, at least in the most
severe cases of SARS-CoV-2 infection. First goal in all alternativee
vaccines for SARS-CoV-2 is boosting immune system as much as
possible then most of them even suggest two shots of vaccination for
building strong immunization against COVID-19. This may lead a
tragedy in vaccinated people by producing cytokine storm. Please note
the most deaths resulting COVID-19 is related to cytokine storm that
causes Acute Respiratory Distress Syndrome (ARDS). Author
estimates any real vaccination may cause a tragedy of cytokine storm
in vaccinated people. Therefore, all volunteers vaccinated people who
have received different doses should be deliberately infected by real
SARS-Cov-2 virus to identify real results of immunity caused by
Please see Figure 1. So the story goes that how to armour this plane
was a real question the Navy was considering during WWII. The
challenge was knowing how to better protect the planes so they didn’t
get shot down. The planes that got shot down were so badly damaged
that any analysis of the wreckage was futile. This phenomenon of
excluding the aircraft that had crashed and never made it back is called
“survivorship bias.” One may concentrate the armor on the places with
the greatest need, where the planes are getting hit the most. But
exactly how much more armor belonged on those parts of the plane?
That was the answer they came to Engineer Wald for. It wasn’t the
answer they got. The armor, said Wald, doesn’t go where the bullet
holes are. It goes where the bullet holes aren’t: on the engines.
Figure 1: Amour the planes where it is getting shot and you are
done right? Wrong. This data wasn’t from the planes that got shot
down, it was from the planes that made it back. That is critical context.
This phenomenon of excluding the aircraft that had crashed and never
made it back is called “survivorship bias.”
Vaccine companies usually try to get as much as possible immunity
in lung of vaccinated people because the lung is the most critical organ
for COVID-19.
But it is wrong because cytokine storm response to vaccination
wasn't considered here.
Authors tested a mRNA type of vaccine made for SARS-Cov-2 in
33 African green monkeys together 200 mice.
Vaccination caused good immunity against SARS-Cov-2, and
vaccinated animals were able to fight off the virus well with resulting
a quickly clearing the virus from their lungs except two monkeys and
9 mice.
Those two monkeys along 9 mice showed syndrome of cytokine
storm in their lungs. This syndrome was acute in one of monkeys and
4 of mice.
Two of the AGMs showed increased levels of plasma IL-6
compared to baseline. We show only results of monkey because
similarly to human.
In Figure 2 shows an IL-6 increase in one of monkeys identification
a cytokine storm due to vaccination against SARS-Cov-2.
Figure 3 shows radiographic changes in SARS-CoV-2 infected
African Green monkey after vaccination that shows ARDS.
ISSN: 2576-3881
Journal of Cytokine Biology
Esmaeil F, J Cytokine Biol 2020, 5:2
Commentary Open Access
J Cytokine Biol, an open access journal Volume 5 • Issue 2 • 34
Figure 2: Radiographic changes in SARS-CoV-2 infected African
Green monkey after vaccination that shows ARDS. Radiographs the
day prior (left picture) and at the time of necropsy (right picture) in
African Green Monkey showing the rapid development of alveolar
lung opacities within the lungs of the animal result of cytokine storm
due to vaccination.
Therefore, it is clear using traditional method of vaccination for
COVID-19 isn't correct way because different people have different
immune response to a vaccine.
It seems developing a smart vaccine for SARS-Cov-2 could be a
good solution for syndrome of cytokine storm because such type of
smart vaccines may deliver necessary dose to different people together
delivering of necessary doses to different organs (for example lung) of
a person.
Claiming that 170 different types of SARS-Cov-2 vaccines produce
enough or more than enough immunity (specially after second shot of
vaccine) sounds terrible without a real test of those vaccines, while all
of producers of such vaccines have plan to start public vaccination
soon. This may lead a tragedy.
Figure 3: Increase of IL-6 in one of monkeys after vaccination that
shows cytokine storm.
Please consider even one in thousand people of vaccinated people
in the world showing syndrome of cytokine storm will cause 7 million
people among 7 billion people then a tragedy of 7 million deaths.
1. Coperchini F, Chiovato L, Croce L, Magri F, Rotondi M (2020) The
cytokine storm in COVID-19: An overview of the involvement of the
chemokine/chemokine-receptor system. Cytokine Growth Factor Rev 53:
2. Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR, et al. (2012)
Into the eye of the cytokine storm. Microbiol Mol Biol Rev 76: 16–32.
3. Costela-Ruiz VJ, Illescas-Montes R, Puerta-Puerta JM, Ruiz C,
Melguizo-Rodrígueza L (2020) SARS-CoV-2 infection: The role of
cytokines in COVID-disease. Cytokine Growth Factor Rev 54: 62–75.
Citation: Esmaeil Farshi (2020) Cytokine Storm Response to COVID-19 Vaccinations. J Cytokine Biol 5: 1000125.
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J Cytokine Biol, an open access journal Volume 5 • Issue 2 • 34
... But at the same time, the vaccine against SARS-Cov-2 can lead to cytokine storm syndrome in some vaccinated people. So, scientists from the USA [136] studied the level of interleukins in 33 monkeys and 200 mice that were vaccinated and found that these animals were able to fight the virus well, which led to the rapid removal of the virus from their lungs, with the exception of two monkeys and 9 mice. These two monkeys, together with mice, had cytokine storm syndrome in the lungs. ...
... This syndrome was acute in one of the monkeys and in 4 mice. Two animals showed elevated plasma levels of IL-6 compared to baseline levels [136]. ...
Full-text available
Coronavirus infection can have various degrees of severity and outcomes. In some cases, it causes excessive production of pro-inflammatory cytokines, a so-called cytokine storm, leading to acute respiratory distress syndrome. Unfortunately, the exact pathophysiology and treatment, especially for severe cases of COVID-19, are still uncertain. Results of preliminary studies showed that immunosuppressive therapy, such as interleukin (IL)-6, IL-1, and TNF-α antagonists commonly used in rheumatology, can be considered as treatment options for COVID-19, especially in severe cases. The review focused on the most common and currently studied monoclonal antibody drugs, as well as up-to-date data on the pathogenesis of COVID-19, host immune response against SARS-CoV-2 and its association with cytokine storm. It also covered effects of interleukin (IL)-6, IL-1, and TNF-α blockers on the course of coronavirus infection and outcome in patients treated for the main autoimmune disease and subsequently infected with COVID-19.
... Notably, a higher antibody titre against SARS-CoV-2 being was associated with more severe disease and suggested to be linked to ADE as one possible probability that was not excluded by the other suggested mechanisms. Moreover, several studies in murine and non-human primate models for SARS-CoV vaccines showed enhanced immunopathology, enhanced respiratory disease [47] or skewing immunological or inflammation-resolving response [42,48,49] on challenge with SARS CoV after immunization and thus the benefit of using SARS-CoV vaccine in humans was doubted [50] and a very interesting commentary that unfortunately has been unnoticed, possibly because of multiple prior rejections at more visible journals, has tested the outcomes of SARS CoV-2 infection in 33 African green monkeys which were vaccinated with mRNA SARS CoV-2 vaccines and ARDS has developed in one [51]. ...
... Approximately 7% of monkeys along with 5% of experimental mice showed cytokine storm in their lungs upon post mRNA vaccination challenge by SARS-CoV-2. It seems developing a vaccine for SARS-Cov-2 that can regulate cytokine storm is needed (Farshi, 2020). ...
Full-text available
The coronavirus disease (COVID-19) is caused by a positive-stranded RNA virus called severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), belonging to the Coronaviridae family. This virus originated in Wuhan City, China, and became the cause of a multiwave pandemic that has killed 3.46 million people worldwide as of May 22, 2021. The havoc intensified with the emergence of SARS-CoV-2 variants (B.1.1.7; Alpha, B.1.351; Beta, P.1; Gamma, B.1.617; Delta, B.1.617.2; Delta-plus, B.1.525; Eta, and B.1.429; Epsilon etc.) due to mutations generated during replication. More variants may emerge to cause additional pandemic waves. The most promising approach for combating viruses and their emerging variants lies in prophylactic vaccines. Several vaccine candidates are being developed using various platforms, including nucleic acids, live attenuated virus, inactivated virus, viral vectors, and protein-based subunit vaccines. In this unprecedented time, 12 vaccines against SARS-CoV-2 have been phased in following WHO approval, 184 are in the preclinical stage, and 100 are in the clinical development process. Many of them are directed to elicit neutralizing antibodies against the viral spike protein (S) to inhibit viral entry through the ACE-2 receptor of host cells. Inactivated vaccines, to the contrary, provide a wide range of viral antigens for immune activation. Being an intracellular pathogen, the cytotoxic CD8+ T Cell (CTL) response remains crucial for all viruses, including SARS-CoV-2, and needs to be explored in detail. In this review, we try to describe and compare approved vaccines against SARS-CoV-2 that are currently being distributed either after phase III clinical trials or for emergency use. We discuss immune responses induced by various candidate vaccine formulations; their benefits, potential limitations, and effectiveness against variants; future challenges, such as antibody-dependent enhancement (ADE); and vaccine safety issues and their possible resolutions. Most of the current vaccines developed against SARS-CoV-2 are showing either promising or compromised efficacy against new variants. Multiple antigen-based vaccines (multivariant vaccines) should be developed on different platforms to tackle future variants. Alternatively, recombinant BCG, containing SARS-CoV-2 multiple antigens, as a live attenuated vaccine should be explored for long-term protection. Irrespective of their efficacy, all vaccines are efficient in providing protection from disease severity. We must insist on vaccine compliance for all age groups and work on vaccine hesitancy globally to achieve herd immunity and, eventually, to curb this pandemic.
As cancer immunotherapies continue to expand across all areas of oncology, it is imperative to establish a standardized approach for defining and capturing clinically important toxicities, such as cytokine release syndrome (CRS). In this paper, we provide considerations for categorizing the variety of adverse events that may accompany CRS and for recognizing that presentations of CRS may differ among various immunotherapies (e.g., monoclonal antibodies, CAR T cell therapies and T cell engagers, which can include bispecific antibodies and other constructs). The goals of this paper are to ensure accurate and consistent identification of CRS in patients receiving immunotherapies in clinical studies to aid in reporting; enable more precise evaluation of the therapeutic risk–benefit profile and cross-study analyses; support evidence-based monitoring and management of important toxicities related to cancer immunotherapies; and improve patient care and outcomes. These efforts will become more important as the number and variety of molecular targets for immunotherapies broaden and as therapies with novel mechanisms continue to be developed.
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mRNA based and adenovirus vectored vaccines, types of nucleic acid-based vaccination, were first ever or first commercially ever approved for the public, respectively. However, these new types possess a potential risk to induce auto-immune diseases e.g. thrombocytopenia and some of these complications might also reason for some of the post vaccination sudden death reports e.g. autoimmune myocarditis and immune induced thromboembolism. 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 also reason for some of the serious adverse effects encountered with administration of convalescent plasma to COVID-19 patients. Importantly, we recommended the CDC to change its neutral recommendation and to advice against administration of nucleic acid-based vaccines to persons complaining from autoimmune diseases. Furthermore, we urge the FDA to consider a reevaluation of the emergency approval granted to Pfizer-BioNTech SARS CoV-2 mRNA (BNT162b2) vaccine as a company specific extra risk might be present wishing for an independent re-evaluation of the important Israeli pan-national experiment. On the other hand, we agree with the EMA decision to reevaluate the safety of Oxford/AstraZeneca (AZD1222) vaccine that ultimately led to a potential thrombosis labelling. Most importantly, a moral, legal, and sacred constitutional public right to know and decide basing on a personalized risk benefit ratio must be secured. Finally, we totally condemn, from a medical point of view, any national policy that necessitates these experimental vaccines and we also condemn the European Court of Human Rights shameful ruling that compulsory vaccination would not contravene human rights law and we suggest that the rapid race to develop and approve SARS CoV-2 vaccines with all its political and economic aspects might eventually end with a man-made Hades that might exceed COVID-19 in its dangers with a potential to replace Nobel Prize with an imprisonment sentence regardless of the signed agreements that will not, ever, secure impunity.
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COVID-19 disease, caused by infection with SARS-CoV-2, is related to a series of physiopathological mechanisms that mobilize a wide variety of biomolecules, mainly immunological in nature. In the most severe cases, the prognosis can be markedly worsened by the hyperproduction of mainly proinflammatory cytokines, such as IL-1, IL-6, IL-12, IFN-γ, and TNF-α, preferentially targeting lung tissue. This study reviews published data on alterations in the expression of different cytokines in patients with COVID-19 who require admission to an intensive care unit. Data on the implication of cytokines in this disease and their effect on outcomes will support the design of more effective approaches to the management of COVID-19.
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The cytokine storm has captured the attention of the public and the scientific community alike, and while the general notion of an excessive or uncontrolled release of proinflammatory cytokines is well known, the concept of a cytokine storm and the biological consequences of cytokine overproduction are not clearly defined. Cytokine storms are associated with a wide variety of infectious and noninfectious diseases. The term was popularized largely in the context of avian H5N1 influenza virus infection, bringing the term into popular media. In this review, we focus on the cytokine storm in the context of virus infection, and we highlight how high-throughput genomic methods are revealing the importance of the kinetics of cytokine gene expression and the remarkable degree of redundancy and overlap in cytokine signaling. We also address evidence for and against the role of the cytokine storm in the pathology of clinical and infectious disease and discuss why it has been so difficult to use knowledge of the cytokine storm and immunomodulatory therapies to improve the clinical outcomes for patients with severe acute infections.
In 2019-2020 a new coronavirus named SARS-CoV-2 was identified as the causative agent of a several acute respiratory infection named COVID-19, which is causing a worldwide pandemic. There are still many unresolved questions regarding the pathogenesis of this disease and especially the reasons underlying the extremely different clinical course, ranging from asymptomatic forms to severe manifestations, including the Acute Respiratory Distress Syndrome (ARDS). SARS-CoV-2 showed phylogenetic similarities to both SARS-CoV and MERS-CoV viruses, and some of the clinical features are shared between COVID-19 and previously identified beta-coronavirus infections. Available evidence indicate that the so called “cytokine storm” an uncontrolled over-production of soluble markers of inflammation which, in turn, sustain an aberrant systemic inflammatory response, is a major responsible for the occurrence of ARDS. Chemokines are low molecular weight proteins with powerful chemoattractant activity which play a role in the immune cell recruitment during inflammation. This review will be aimed at providing an overview of the current knowledge on the involvement of the chemokine/chemokine-receptor system in the cytokine storm related to SARS-CoV-2 infection. Basic and clinical evidences obtained from previous SARS and MERS epidemics and available data from COVID-19 will be taken into account.