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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
... Cytotoxic T-cells and Natural Killer cells are important for generating an effective immune response against viruses in humans [33]. Our study found that increased cytokine levels and lymphopenia (significantly reduced CD4+ and CD8+ T cells) correlated with disease severity of COVID-19. ...
... This vaccine should utilize engineered peptides that strongly bind to the spike protein of the virus, and use these peptides to trigger the breakdown of viral proteins within cells [29,30]. This type of vaccine shouldn't cause a cytokine storm [33]. The mRNA in the vaccine should encode a stable form of the spike protein, which will be processed by immune cells in the lymph nodes and recognized by other immune cells. ...
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Coronaviruses are significant pathogens for humans. Our findings suggest that antibodies may not have a crucial role in long-term immunity against COVID-19, but T cells, a type of white blood cell, could play a critical role. T cells have long-term memory in the blood. Investigating mild cases of COVID19 in children is key to understanding the disease, as it may uncover important protective mechanisms and therapeutic targets. Children's milder response to COVID-19 compared to adults suggests that children have a higher resistance to the virus due to their innate immune system. Our results indicate that phagocytes, a component of the innate immune system, play a significant role in eliminating COVID-19 in both mice and humans. We also found that CD4+ T cells activate B cells and play a crucial role in primary infections. Kids have higher levels of natural antibodies (IgM and IgG) compared to adult patients, and the number of γδ T cells increases both locally and systemically in kids with COVID-19, but decreases in adults with severe symptoms. Our observations have important implications for developing novel vaccines and therapies for COVID-19. To produce a vaccine, the following factors must be considered: 1) phagocytes, 2) natural antibodies, 3) T cells, and 4) white blood cells. The vaccine should be based on T cells instead of antibodies and should also boost the innate immune system, including phagocytes. A novel vaccine eliciting a protective immune response against SARS-Cov-2 is suggested.
... It had been previously reported that vaccination with COVID-19 vaccine induces expression of pro-inflammatory cytokines in mice models [29]. In order to further explore the robustness of immune response induced by Janssen COVID-19 vaccine and supplements in BALB/c mice, the present study determined the splenocyte expression of Interleukin-6 (IL-6) and Interleukin-10 (IL-10) cytokines in experimental groups. ...
... Cytokine storms have been observed in subjects immunized with COVID-19 vaccines [29]. Interleukin-6 (IL-6) and Interleukin-10 (IL-10) have been reported to be important inflammatory cytokines and major characteristics of a SARS-CoV-2 hyper-inflammatory response [32]. ...
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Evidence of efficacy and toxicity of oral selenium supplementation in vaccine administration against severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) in mice models is scarce. In this study, 4 × 109 virus particles (40 µL) dose of Janssen COVID-19 intramuscular injection vaccine was supplemented with a commercial selenium supplement and sodium selenite orally in BALB/c mice (N = 18). Qualitative determination of anti-spike IgG antibody response using indirect Enzyme-Linked Immunosorbent Assay (ELISA) showed significant (p ≤ 0.001) increase in anti-spike IgG antibody response for mice groups immunized with vaccine and supplemented selenium. Furthermore, cytokine profiling using real-time quantitative polymerase chain reaction also showed an increase in IL-6 and IL-10 mRNA levels normalized using hypoxanthine phosphoribosyl transferase 1 (Hprt1) and glyceraldehyde 3-phosphate dehydrogenase (Gadph) housekeeping genes. There was no statistical significance (p < 0.465) among treated and untreated groups for alanine transaminase (ALT), aspartate transaminase (AST), urea, and creatinine parameters. The study presents preliminary findings and suggests that supplementing Janssen COVID-19 vaccines with selenium can generate more robust immune responses.
... 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]. ...
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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.
... SARS-CoV-2 severity and mortality are impacted by innate and adaptive immune responses to two primary immune dysregulations. One is cytokine storm with overproduction of pro-inflammatory cytokines, which leads to immune exhaustion, which was also reported experimentally following vaccination 22 . The other is a dysregulation of lymphocytes that leads to B-cell lymphopenia and is characterized by CD4 + T cells 23 . ...
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The breakthrough infection following COVID-19 vaccination has been a subject of concern recently. Evidence suggests that COVID-19 vaccine efficacy diminishes over time due to multiple factors related to the host, and vaccine. Coinfection with other pathogens was claimed earlier as a contributing cause for this phenomenon. Hence, we aimed to stratify the association of post-COVID-19 vaccination breakthrough coinfection with Toxoplasma gondii (T. gondii) and its impact on disease severity. This cross-sectional study included 330 COVID-19-vaccinated patients confirmed by RT-PCR. They were also screened for anti- T. gondii antibodies using ELISA. Toxoplasma seropositive cases’ whole blood was screened for DNA using PCR to correlate results with COVID-19 severity. Out of 330 COVID-19 vaccinated patients with breakthrough infection, 34.5% (114 patients) showed positivity for Toxoplasma IgG by ELISA, and none of the cases was IgM positive. Eleven patients (9.6%) of the IgG-positive cases were positive by PCR. Positive PCR cases correlated positively with the Toxoplasma IgG titer (P < 0.001), and the Cutoff point was 191.5. Molecular analysis of Toxoplasma and COVID-19 severity showed that 8 (72.7%), 1 (9.1%), and 2 cases (18.2%) had mild, moderate, and severe courses of the disease, respectively, with no significant correlation. Our study reported a heightened prevalence of latent toxoplasmosis among mild cases of COVID-19 breakthrough infection. Nevertheless, a discernible correlation between latent toxoplasmosis and COVID-19 severity is lacking. Hence, implementing studies on a larger scale could provide a more comprehensive comprehension of this association.
... The paper also presents a method of protecting humans against coronavirus infections, particularly SARS-CoV-2, using a MMR vaccine that includes at least one of the measles, mumps, or rubella vaccines or a combination of two or three of them. The paper explains that all coronaviruses trigger antibody and T cell responses, but antibody levels tend to wane faster than T cells [8][9][10][11]. The MMR vaccine is shown to have long-lasting effects, lasting for at least several years, which could potentially provide protection against COVID-19. ...
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The MMR (measles, mumps, and rubella) vaccine has been found to generate protective immunity against severe SARS-CoV-2 infections. Analysis of 21 countries that have had general MMR vaccination over the last few years has shown near-zero fatality rates due to COVID-19. This phenomenon could be related to the mild or no effects of COVID-19 in children who have received the MMR vaccine at birth. Our clinical study involving 200 adults, 100 of whom were vaccinated with MMR, demonstrated that the vaccine provides immunity against severe COVID-19 infection in a human challenge. There are several similarities between the SARS-CoV-2 virus and the measles, mumps, and rubella viruses, and the MMR vaccine behaves like a T-cell induced vaccine that can be effective against COVID-19. The MMR vaccine has been in use for many years without side effects, and its global use against COVID-19 could be a viable option as it provides immunity for several years, which is longer than the currently available COVID-19 vaccines.
... CRS is a supraphysiologic response driven by the immune system. It has been commonly observed in sepsis and other infections, including those related to COVID-19, and as an ontarget AE of T cell-mediated therapies or in response to other therapies such as COVID-19 mRNA vaccines [11]. CRS is initiated by the activation of T cells and mediated by cytokines produced by macrophages and other myeloid cells. ...
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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.
... Last possible reason is inordinate immune reaction after COVID-19 vaccination. Vaccination against COVID-19 lead to release cytokines which can cause abnormal immune reaction like ITP [9,10]. ...
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Thrombocytopenia is one of the rare signs of both the coronavirus disease 2019 (COVID-19) and COVID-19 vaccination. An 85-year-old man was diagnosed with immune thrombocytopenia and COVID-19, 7 days after COVID-19 vaccination. The patient was successfully treated with a short course of intravenous immunoglobulin and oral corticosteroids.
... 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). ...
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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.
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A COVID-19 é uma doença infecciosa causada pelo coronavírus SARS-CoV-2, que começou em Wuhan (China), no final de 2019, e se espalhou por todo o mundo. Quando o paciente entra no quadro clínico grave da doença, o sistema imunológico começa a produzir de forma descontrolada citocinas pró-inflamatórias, fenômeno conhecido como ``tempestade de citocinas'', causando a Síndrome do Desconforto Respiratório Agudo (SDRA) e, a partir desse momento, o quadro clínico do paciente é crítico, sendo necessário internação em Unidades de Terapia Intensiva (UTI). Neste artigo, elaboramos um modelo matemático que descreve o problema da dinâmica temporal da infecção do SARS-CoV-2 em pacientes com manifestações clínicas grave ou crítica da COVID-19 e, como consequência disso, o problema inclui a ``tempestade de citocinas''. O modelo consiste em um sistema de cinco equações diferenciais ordinárias não-lineares de primeira ordem, que é resolvido numericamente usando o Software Mathematica. Dentre as cinco variáveis envolvidas no sistema, a carga viral foi a mais detalhada, pois ela descreve o nível de RNA do SARS-CoV-2 nos pacientes. Foram apresentados e interpretados os perfis da carga viral, em várias situações, em que os pacientes evoluíram para a cura ou óbito. Para a carga viral, o modelo apresentou um erro relativo de 19,13% quando comparado com dados clínicos da literatura existente.
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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.
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.
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.