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Cytokine Storms & COVID-19

The introduction of viral particles and live viruses into the human body and its organs can present a multitude of biological malfunctions. In some instances the body can overcompensate, as a reaction to viral material throughout organs and other areas of the body. This dramatic response creates a flood of mass inflammation, which can spread to multiple organs causing destruction to the natural function of the human body.

A Cytokine Storm is an overproduction of immune cells, it’s symptoms including mass inflammation, fever, central nervous system problems, blood clots, organ damage, pneumonia, organ failure, and death. Although there are many causes for a Cytokine Storm, researchers believe that this medical phenomenon also occurs as a result of COVID-19 infections.

Cytokine Storm is also known as hypercytokinemia, and can be thought of as a sort of “hyper inflammation” which occurs from a variety of sources, result devastating consequences. A relatively new concern with COVID-19, Cytokine Storms can be caused by the infection of SARS-CoV-2. Predicting who is at risk of Cytokine Storm, in addition to what triggers the immune system overreaction the body’s immune system depends greatly on the individual and a variety of factors, making it difficult to pinpoint who’s immune system will react to what virus.

As of February 2, 2022, 5,680,741 deaths have been reported to the World Health Organization1 (WHO) due to SARS-CoV-2. How many of these deaths have occurred as a result of Cytokine Storms? The following eleven studies from scientists and researchers around the world, provide a closer insight to what is known, available treatments, and the possibilities of viral-activated cytokine storms, as a result of COVID-19.

1) Cytokine Storm

Cytokine Storm2

Cytokine storm is an umbrella term encompassing several disorders of immune dysregulation characterized by constitutional symptoms, systemic inflammation, and multiorgan dysfunction that can lead to multiorgan failure if inadequately treated”

Cytokine storm and cytokine release syndrome are life-threatening systemic inflammatory syndromes involving elevated levels of circulating cytokines and immune-cell hyperactivation that can be triggered by various therapies, pathogens, cancers, autoimmune conditions, and monogenic disorders.”

“Nearly all patients with cytokine storm are febrile, and the fever may be high grade in severe cases. In addition, patients may have fatigue, anorexia, headache, rash, diarrhea, arthralgia, myalgia, and neuropsychiatric findings.

“These symptoms may be due directly to cytokine-induced tissue damage or acute-phase physiological changes or may result from immune-cell–mediated responses.”

“Cases can progress rapidly to disseminated intravascular coagulation with either vascular occlusion or catastrophic hemorrhages, dyspnea, hypoxemia, hypotension, hemostatic imbalance, vasodilatory shock, and death.”

“Many patients have respiratory symptoms, including cough and tachypnea, that can progress to acute respiratory distress syndrome (ARDS), with hypoxemia that may require mechanical ventilation. The combination of hyperinflammation, coagulopathy, and low platelet counts places patients with cytokine storm at high risk for spontaneous hemorrhage.”

“In short, cytokine storm involves an immune response that causes collateral damage, which may be greater than the immediate benefit of the immune response.”

“Cytokine storm can also result from naturally occurring microbial infections.”

“Disseminated viral infections can also induce profound cytokine storm.”

“Patients with hyperinflammatory responses to microbes often have defects in pathogen detection, effector and regulatory mechanisms, or resolution of inflammation.”

Cytokine Storms and COVID-19

“Covid-19, which is caused by SARS-CoV-2, is characterized by heterogeneous symptoms ranging from mild fatigue to life-threatening pneumonia, cytokine storm, and multiorgan failure.”

“Cytokine storm was also reported in patients with SARS and was associated with poor outcomes.”

“Although the mechanisms of lung injury and multiorgan failure in Covid-19 are still under investigation, reports of hemophagocytosis and elevated cytokine levels — as well as beneficial effects of immunosuppressant agents — in affected patients, particularly those who are the most severely ill, suggest that cytokine storm may contribute to the pathogenesis of Covid-19.”

“Laboratory test results reflecting hyperinflammation and tissue damage were found to predict worsening outcomes in Covid-19.”

“Although immunologic dysregulation has been observed in severe cases of Covid-19, it is not known whether immune hyperactivity or a failure to resolve the inflammatory response because of ongoing viral replication or immune dysregulation underlies severe cases.”

“Host immune responses and immune-related symptoms are extremely variable between asymptomatic patients (who have effective control of SARS-CoV-2) and patients with severe Covid-19 (who are unable to control the virus), which suggests that host immune dysregulation contributes to pathogenesis in some cases.”

“[I]t is now clear that patients with SARS-CoV-2 infection can be asymptomatic or can have acute Covid-19 with heterogeneous severity, a chronic course of Covid-19, or multisystem inflammatory syndrome.”

“A critical question concerns the factors that contribute to the severe cytokine storm–like phenotype observed in a small fraction of patients. Coexisting conditions such as hypertension, diabetes, and obesity are associated with more severe cases of Covid-19, possibly because of the preexisting chronic inflammatory state or a lower threshold for the development of organ dysfunction from the immune response.”

“First, cytokine storm triggered by infection with SARS-CoV-2 may require different therapies from those used for cytokine storm due to other causes.”

“[B]locking cytokine signaling may actually impair clearance of SARS-CoV-2, increase the risk of secondary infections, and lead to worse outcomes, as seen with influenza virus.”

“[T]he primary site of infection and disease most likely contributes to differences in immune responses and mechanisms underlying the cytokine storm”

“[L]ymphopenia is not often observed in cytokine storm disorders, but it is a hallmark of severe Covid-19. It is currently unclear whether the lymphopenia observed in Covid-19 is due to tissue infiltration or destruction of lymphocytes.”

“[C]lotting issues can occur across cytokine storm disorders, but thromboembolic events appear to be more frequent in Covid-19–associated cytokine storm.”

COVID-19 Treatment

  • “Canakinumab, an anti–interleukin-1β monoclonal antibody, and anakinra are both being studied for Covid-19–induced ARDS.
  • Acalabrutinib, a selective inhibitor of Bruton tyrosine kinase that regulates B-cell and macrophage signaling and activation, may have promise for dampening the hyperinflammatory response in Covid-19.
  • JAK1 and JAK2 inhibitors, which are approved for the treatment of a number of autoimmune and neoplastic conditions, have the potential to inhibit signaling downstream of type I interferon, interleukin-6 (and other gp130 family receptors), interferon-γ, and interleukin-2, among other cytokines.
  • Much like anti–interleukin-6 antibody therapy, inhibition of Bruton tyrosine kinase and JAK could prove to be damaging or unhelpful if given too soon, when the immune response to SARS-CoV-2 is critical in controlling viral replication and clearance.”
  • [T]reatment strategy for cytokine storm involves supportive care to maintain critical organ function, control of the underlying disease and elimination of triggers for abnormal immune system activation, and targeted immunomodulation or nonspecific immunosuppression to limit the collateral damage of the activated immune system.

Fajgenbaum DC, June CH. Cytokine Storm. N Engl J Med. 2020 Dec 3;383(23):2255-2273. doi: 10.1056/NEJMra2026131. PMID: 33264547; PMCID: PMC7727315.

2) Immunopathogenesis and treatment of cytokine storm in COVID-19

A group of eight researchers, (five from South Korea, two from Austria, one from Denmark) studied the phenomenon and treatment options available for cytokine storm in COVID-19.

Immunopathogenesis and treatment of cytokine storm in COVID-193

“Cytokine storm is a condition of uncontrolled systemic hyper-inflammation caused by cytokine excess, leading to multi-organ failure and even death”

“The concept of cytokine storm was initially recognized in acute graft-versus-host disease in the process of hematopoietic stem cell transplantation”

“Researchers have since revealed that cytokine storm occurs in various diseases, such as malignancy, rheumatologic disease, and sepsis syndrome and is a concern in COVID-19”

“Severe coronavirus disease 2019 (COVID-19) is characterized by systemic hyper-inflammation, acute respiratory distress syndrome, and multiple organ failure.”

Severe COVID-19

“Studies have indicated that the rapid clinical deterioration and high mortality risk in severe COVID-19 could be related to cytokine storm”

[P]atients admitted to the intensive care unit (ICU) had higher cytokine levels of IL-2, IL-7, IL-10, granulocyte colony-stimulating factor (G-CSF), IP10, MCP1, macrophage inflammatory protein 1- α, and TNF-α than those not requiring ICU treatment”

“Another study showed that IL-6 was more elevated in non-survivors than survivors from COVID-19, suggesting that COVID-19 mortality might be due to virus-activated cytokine storm

Kim JS, Lee JY, Yang JW, Lee KH, Effenberger M, Szpirt W, Kronbichler A, Shin JI. Immunopathogenesis and treatment of cytokine storm in COVID-19. Theranostics. 2021 Jan 1;11(1):316-329. doi: 10.7150/thno.49713. PMID: 33391477; PMCID: PMC7681075.

3) COVID-19: consider cytokine storm syndromes and immunosuppression

On March 3rd, 2020 six scientists from the UK on behalf of the HLH Across Speciality Collaboration pointed to what they called “accumulating evidence” that suggests many severe COVID-19 cases may have in fact been a result of cytokine storms.

COVID-19: consider cytokine storm syndromes and immunosuppression4

“As of March 12, 2020, coronavirus disease 2019 (COVID-19) has been confirmed in 125 048 people worldwide, carrying a mortality of approximately 3·7%,1 compared with a mortality rate of less than 1% from influenza. There is an urgent need for effective treatment. Current focus has been on the development of novel therapeutics, including antivirals and vaccines.”

“Accumulating evidence suggests that a subgroup of patients with severe COVID-19 might have a cytokine storm syndrome.”

“We recommend identification and treatment of hyperinflammation using existing, approved therapies with proven safety profiles to address the immediate need to reduce the rising mortality.”

“As during previous pandemics (severe acute respiratory syndrome and Middle East respiratory syndrome), corticosteroids are not routinely recommended and might exacerbate COVID-19-associated lung injury.7 However, in hyperinflammation, immunosuppression is likely to be beneficial”

“All patients with severe COVID-19 should be screened for hyperinflammation using laboratory trends (eg, increasing ferritin, decreasing platelet counts, or erythrocyte sedimentation rate) and the HScore11 (table ) to identify the subgroup of patients for whom immunosuppression could improve mortality.”

“Therapeutic options include steroids, intravenous immunoglobulin, selective cytokine blockade (eg, anakinra or tocilizumab) and JAK inhibition.”

Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16. PMID: 32192578; PMCID: PMC7270045.

4) Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China

Five researchers from Wuhan, China conducted a study of 68 death cases (forty-five percent) and 82 discharged cases (fifty-five percent) with laboratory-confirmed infection of SARS-CoV-2. Their findings indicated that the mass quantity of casualties might have been a result of “virus-activated cytokine storm” in addition to fulminant myocarditis -fatal inflammation of the heart. As of February 2nd. 2022 the World Health Organization (WHO) has reported 880,580 “COVID-19 deaths” in America. how many of these deaths—or severe hospitalizations—have been a result of virus-activated cytokine storms throughout the body?

Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China5

“It should be noted that patients with cardiovascular diseases have a significantly increased risk of death when they are infected with SARS-CoV-2”

“The results obtained from this study also suggest that COVID-19 mortality might be due to virus-activated “cytokine storm syndrome” or fulminant myocarditis.”

“Laboratory results showed that there were significant differences in white blood cell counts, absolute values of lymphocytes, platelets, albumin, total bilirubin, blood urea nitrogen, blood creatinine, myoglobin, cardiac troponin, C-reactive protein (CRP) and interleukin-6 (IL-6) between the two groups.”

“IL-6 is an important pro-inflammatory cytokine that has pleiotropic effect”

“A few IL-6 inhibitors have been used in auto-immune disorders and related cytokine storm”

“Many studies have demonstrated that IL-6 is significantly elevated in patients with COVID-19.”

“[S]tudies have suggested that IL-6 is predictive of poor outcomes in COVID-19”

“[M]any clinicians are currently using glucocorticoids as an empirical treatment for severe COVID-19. Unlike specific cytokine inhibitors, glucocorticoids are believed to be effective against cytokine storm by inhibiting multiple inflammatory targets.”

“Glucocorticoids not only have excellent immunosuppressive effects on immune cells, but also have anti-inflammatory effects by inhibiting the production of major inflammatory molecules, including prostaglandins and leukotrienes.”

“Evidence supporting the use of glucocorticoids in severe COVID-19, however, is lacking 6768. Although this matter is still argued, several studies have positively reported steroid effects in severe COVID-19”

“Colchicine is an anti-inflammatory drug that is commonly used in gouty arthritis.”

“A few studies are investigating the clinical effects of colchicine on COVID-19. A recent RCT demonstrated that colchicine delays the time to clinical deterioration in COVID-19.”

“Although this matter is still argued, several studies have positively reported steroid effects in severe COVID-19”

“[A] few researchers have proposed the use of low-dose radiation therapy to control hyper-inflammatory states in severe COVID-19”

“According to the cited studies, low-dose radiation (usually < 1.0 Gy) has immune-modulating effects on immune cells, changing them into an anti-inflammatory phenotype. Thus, in the patients with COVID-19 and ARDS, low-dose radiation on both lungs could potentially facilitate clinical improvements in hyper-inflammatory lung injury.”

Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China. Intensive Care Med. 2020 May;46(5):846-848. doi: 10.1007/s00134-020-05991-x. Epub 2020 Mar 3. Erratum in: Intensive Care Med. 2020 Apr 6;: PMID: 32125452; PMCID: PMC7080116.

A study in France used radiation to treat COVID-19, advocating its use to combat the inflammation of lung tissue. While this may be a viable option to prevent the infamous coronavirus, what long term effects can occur in mass lung radiation as a procedural regimen? The French Researchers used radiation was performed with low-energy X-rays.

Low dose lung radiotherapy for COVID-19-related cytokine storm syndrome: Why not?6

“Many irradiated patients have therefore received doses of diffused radiation in their lungs that could be “protective” (?) against a severe form of COVID-19 pneumonitis.”

“It may be interesting to list these patients irradiated and infected with SARS-CoV-2 (by selecting those who received a dose of diffuse radiation of the order of Gy) and to study whether or not they were affected by a “cytokine storm” leading to severe pneumonitis [inflammation of lung tissue].”

“In addition to the doses received at the pulmonary level, we also know that any irradiation, especially large abdominopelvian, is responsible for a more or less marked lymphopenia: given what has been said above, could this lymphopenia prove to be “protective” against severe pulmonary forms of COVID-19? In this case, it would be almost all radiotherapy patients that should be analyzed…”

“Under these conditions, one can legitimately raise the problem of a low-dose irradiation (less than 1 Gy?) of both lungs, irradiation which, given what has been written above, should lead to a depletion of the order of 50% of lymphocyte infiltration and ensure immunosuppression (essentially local) likely to be beneficial to the patient.”

Cosset JM, Deutsch É, Bazire L, Mazeron JJ, Chargari C. Irradiation pulmonaire à faible dose pour l’orage de cytokines du COVID-19 : pourquoi pas ? [Low dose lung radiotherapy for COVID-19-related cytokine storm syndrome: Why not?]. Cancer Radiother. 2020 Jun;24(3):179-181. French. doi: 10.1016/j.canrad.2020.04.003. Epub 2020 May 1. PMID: 32389579; PMCID: PMC7252150.

6) Is severe COVID-19 a cytokine storm syndrome: a hyperinflammatory debate

On September 1st, 2021 two researchers (London, and USA) advocated that cytokine storm therapy was suggested early on in the pandemic, despite being criticized by the medical dictatorship. Hyper inflammation is reported and confirmed by the duo of being a symptom of COVID—19. The team believes that the inflammation is modifiable which means proper treatment could result in saving countless lives, as opposed to approaching it from a universal perspective designed to boost vaccine sales.

Is severe COVID-19 a cytokine storm syndrome: a hyperinflammatory debate7

The COVID-19 pandemic is a global public health crisis with considerable mortality and morbidity.”

“A role for cytokine storm and therapeutic immunomodulation in a subgroup of patients with severe COVID-19 was proposed early in the pandemic.”

“The concept of cytokine storm in COVID-19 has been criticised, given the lack of clear definition and relatively modest cytokinaemia (which may be necessary for viral clearance) compared with acute respiratory distress syndrome and bacterial sepsis. Here we consider the arguments for and against the concept of cytokine storm in COVID-19.

“Recent findings: Several criteria have been proposed to identify the subgroup of COVID-19 patients exhibiting a cytokine storm.”

“The beneficial effects of corticosteroids and interleukin-6 inhibition suggest that inflammation is a modifiable pathogenic component of severe COVID-19.”

“The presence of genetic polymorphisms and pathogenic auto-autoantibodies in severe COVID-19 also suggests a significant contribution of immune dysregulation to poor outcomes.”

“Summary: Hyperinflammation is a key component of severe COVID-19, residing underneath the cytokine storm umbrella term, associated with poor outcomes.”

“Better understanding of the aetiopathogenesis, with identification of biomarkers to predict treatment responses and prognosis, will hopefully enable a stratified and ultimately precision medicine approach.”

Mehta P, Fajgenbaum DC. Is severe COVID-19 a cytokine storm syndrome: a hyperinflammatory debate. Curr Opin Rheumatol. 2021 Sep 1;33(5):419-430. doi: 10.1097/BOR.0000000000000822. PMID: 34264880; PMCID: PMC8373392.

7) Calming the Storm: Natural Immunosuppressants as Adjuvants to Target the Cytokine Storm in COVID-19

On January 7th, 2021 four scientists from India refferred to thje COVID-19 pandemic as a “global health crisis with no specific antiviral”, citing the lack of effective vaccine to fully prevent infection upon exposure, despite the mandated injections. The coronavirus concoctions rolled out December 13th, 2020 in New York City8. Reported higher levels of cytokine as a result of a SARS-CoV-2 infection. the team suggested plant substances to combat the effects of Cytokine Storms such as curcumin, luteolin, piperine, resveratrol.

Calming the Storm: Natural Immunosuppressants as Adjuvants to Target the Cytokine Storm in COVID-19

“The COVID-19 pandemic has caused a global health crisis, with no specific antiviral to treat the infection and the absence of a suitable vaccine to prevent it.”

“While some individuals contracting the SARS-CoV-2 infection exhibit a well coordinated immune response and recover, others display a dysfunctional immune response leading to serious complications including ARDS, sepsis, MOF; associated with morbidity and mortality.”

“Studies revealed that in patients with a dysfunctional immune response, there is a massive cytokine and chemokine release, referred to as the ‘cytokine storm’.”

“As a result, such patients exhibit higher levels of pro-inflammatory/modulatory cytokines and chemokines like TNFα, INFγ, IL-1β, IL-2, IL-4, IL-6, IL-7, IL-9, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, MCSF, HGF and chemokines CXCL8, MCP1, IP10, MIP1α and MIP1β.”

“Targeting this cytokine storm is a novel, promising treatment strategy to alleviate this excess influx of cytokines observed at the site of infection and their subsequent disastrous consequences.”

“Natural immunosuppressant compounds, derived from plant sources like curcumin, luteolin, piperine, resveratrol are known to inhibit the production and release of pro-inflammatory cytokines and chemokines.”

“This inhibitory effect is mediated by altering signal pathways like NF-κB, JAK/STAT, MAPK/ERK that are involved in the production and release of cytokines and chemokines.”

“The use of these natural immunosuppressants as adjuvants to ameliorate the cytokine storm; in combination with antiviral agents and other treatment drugs currently in use presents a novel, synergistic approach for the treatment and effective cure of COVID-19.”

“This review briefly describes the immunopathogenesis of the cytokine storm observed in SARS-CoV-2 infection and details some natural immunosuppressants that can be used as adjuvants in treating COVID-19 disease.”

Peter AE, Sandeep BV, Rao BG, Kalpana VL. Calming the Storm: Natural Immunosuppressants as Adjuvants to Target the Cytokine Storm in COVID-19. Front Pharmacol. 2021 Jan 27;11:583777. doi: 10.3389/fphar.2020.583777. PMID: 33708109; PMCID: PMC7941276.

8) Cytokine Storm in COVID-19—Immunopathological Mechanisms, Clinical Considerations, and Therapeutic Approaches: The REPROGRAM Consortium Position Paper

A group of nine researchers from different countries [United States, Australia, Canada, Germany, India, and Poland] also describe cytokine storms in COVID-19 patients. They highlight the lack of available treatment options for coronavirus induced cytokine storms.

Cytokine Storm in COVID-19—Immunopathological Mechanisms, Clinical Considerations, and Therapeutic Approaches: The REPROGRAM Consortium Position Paper9

“Because of the association between cytokine storm and severe COVID-19 complications, we propose a cytokine storm-based diagnosis and management workflow for patients with or suspected of COVID-19”

“Our proposal expands on the multidisciplinary evidence-based guidelines currently used in the diagnosis and treatment of cytokine storm linked macrophage activation syndrome and sHLH. The Surviving Sepsis Campaign COVID-19 panel recommends the use of moderate-dose steroids for intubated patients with ARDS (10 mg dexamethasone daily, or 60 mg/day methylprednisolone).”

“The diagnosis and management of cytokine storm are clinically challenging and controversial due to lack of proven treatment.”

“We recommend longitudinal follow-up of COVID-19 patients with and without the cytokine storm to understand the specific immunopathological mechanisms and biomarkers for severe disease.”

“After cytokine storm resolves, an immunologic memory of the SARS-CoV-2 infection will likely persist (124), raising the possibility of either relapse or reinfection in previously COVID-19 positive patients who subsequently cleared the infection.”

“Limiting damage from a hyperimmune response during both the acute phase and the cytokine storm is a target for further research. There could be a decoupling mechanism of cytokines that may attenuate the cytokine storm and preserve memory (110).”

“Hypercytokinemia [cytokine storm] is an unregulated hyperinflammatory response that results from the systemic spread of a localized inflammatory response to viral or bacterial infection.”

“Elevated cytokine levels result in endothelial dysfunction, vascular damage, and paracrine/metabolic dysregulation, thereby damaging multiple organ systems.”

“Mechanisms of SARS-CoV-2 associated cytokine storm and associated damages. Infection with SARS-CoV 2 can stimulate a hyperinflammatory immune response wherein epithelial-cell-mediated production of reactive oxygen species (ROS) can cause cell death.”

“ROS can also stimulate the synthesis of NLRP3 and NF-κB which contribute to increased cytokine levels, and thus, the cytokine storm. This essentially causes immune invasion which can lead to clinically relevant conditions such as ARDS, sepsis, MODS and potentially even death.”

“We propose that the immune system cytokine network may also communicate with the central nervous system (CNS) cytokine network, especially when the blood-brain-barrier (BBB) is compromised.”

[L]eading to neural tissue damage through neuroinflammation, increased oxidative stress and excitotoxicity, and dysfunction in synaptic pruning”

“Although the association between cytokine storm and the radiological manifestations of COVID-19 pneumonia infection require further investigation, computer assisted tomography (CT), the lungs of patient with COVID-19 pneumonia typically demonstrate findings typical of underlying hyperinflammatory pathway.”

“On CT chest, the lungs typically demonstrate ground-glass opacities (subpleural, peripheral and bilateral), bronchovascular thickening within lesions, smooth or irregular interlobular or septal thickening, air space consolidation, traction bronchiectasis, ill-defined margins, air bronchograms, and thickening of the adjacent pleura.”

“The phenomenon has been implicated in critically ill patients infected with SARS-CoV-2, the novel coronavirus implicated in COVID-19.”

“Critically ill COVID-19 patients experiencing cytokine storm are believed to have a worse prognosis and increased fatality rate. In SARS-CoV-2 infected patients, cytokine storm appears important to the pathogenesis of several severe manifestations of COVID-19: acute respiratory distress syndrome, thromboembolic diseases such as acute ischemic strokes caused by large vessel occlusion and myocardial infarction, encephalitis, acute kidney injury, and vasculitis (Kawasaki-like syndrome in children and renal vasculitis in adult).”

Bhaskar S, Sinha A, Banach M, Mittoo S, Weissert R, Kass JS, Rajagopal S, Pai AR, Kutty S. Cytokine Storm in COVID-19-Immunopathological Mechanisms, Clinical Considerations, and Therapeutic Approaches: The REPROGRAM Consortium Position Paper. Front Immunol. 2020 Jul 10;11:1648. doi: 10.3389/fimmu.2020.01648. PMID: 32754159; PMCID: PMC7365905.

9) Attenuating the Effects of Novel COVID-19 (SARS-CoV-2) Infection-Induced Cytokine Storm and the Implications

On April 16th, 2021 ten researchers from Nigeria, two from Bangladesh, one from Malaysia, and one from India describe what they refer to as “COVID-19 induced cytokine storm” causing irregularities and hyper inflammation. The team highlights the benefits of vitamins, such as Vitamin D to combat COVID-19. Their research showed that Vitamin D has been shown to suppress cytokine production for those diagnosed with COVID-19. Zinc, Vitamin C, and many others were mentioned, each describing their beneficial reported improvements to COVID-19 infected individuals.

Attenuating the Effects of Novel COVID-19 (SARS-CoV-2) Infection-Induced Cytokine Storm and the Implications10

“Markers of COVID-19-Induced Cytokine Storm”

“Generally, cytokine storms are diagnosed in the form of the underlying medical condition. Therefore, a viral infection-induced cytokine storm is different from a macrophage activation syndrome induced by autoimmune defects such as systemic juvenile idiopathic arthritis (JIA) and in lupus or familial hemophagocytic lymphohistiocytosis (HLH), which is induced by certain genetic syndromes.”

“The symptoms of cytokine storms include fatigue, fever, chills, nausea, emesis, headache, cough, seizures, tremor, dyspnea, lethargy, and rash. Other symptoms include increased blood clotting, low blood pressure, multiple organ failure, and death.”

The quick and early prediction of hypercytokinemia through specific biological markers would prevent many deaths. This use of these markers would allow for closer clinical monitoring and aggressive supportive treatment to avoid a poor prognosis (Figure 3). The clinical markers (Table 1) that can diagnose tissue damage in COVID-19 infection include serum chemistry and hematological parameters.”


“Vitamin D has also been shown to suppress cytokine production in COVID-19 patients.”

“Vitamin D binds with the vitamin D receptor (VDR) on Th17 cells and suppresses the production of the IL-17 by inducing C/EBP homologous protein (CHOP) expression. Consequently, the recruitment of neutrophils is impaired.”

“Data from observational studies suggest that vitamin D supplementation can reduce the risk of developing respiratory infections, especially in vitamin D-deficient people.”


“Zinc is an indispensable trace element involved in gene expression, protein folding, enzymatic reactions, and physiological processes.”

“In combating SARS-CoV-2 viremia and its associated cytokine storm, zinc is vital in decreasing oxidative stress and optimizing immune function.”

“Zinc modulates the activities of immune cells.”

“Interestingly, significantly lower levels of Zinc have been found in COVID-19 patients than in uninfected persons.”

“This low zinc level has also increased the risk of complications by 5-fold. Also, in the treatment of COVID-19, zinc supplementation has proved to be essential due to the micronutrient’s natural antiviral and immunomodulatory properties. It is useful for the majority of the population, particularly those having suboptimal zinc levels.”

Polyunsaturated Fatty Acids

“Omega-3 fatty acids are responsible for modulating monocyte and lymphocyte functions and modify host immunity during inflammatory disease.183,184

Omega-3 fatty acids are made up of eicosapentaenoic and docosahexaenoic acids, which extensively enhance an immune response to viral infections.”


“Clinical trials using only medicinal plants for the prevention and treatment of COVID-19 are scarce.”

“In Iran, clinical studies have been carried out to investigate the anti-COVID-19 efficacy of the combination of several medicinal plants such as licorice, mallow, turmeric, echinacea, ginger, sage, fennel, and St. John’s wort.11


The COVID-19-induced cytokine storm is characterized by immune dysregulation and hyperinflammation. It is also associated with tissue damage, multi-organ failure, and death. The early diagnosis and aggressive mitigation of cytokine storms are essential to reduce COVID-19 morbidities and mortalities effectively.”

“Clinical data suggests that specific hyper-inflammation markers have proven to be accurate and reliable in distinguishing between mild and severe cases of COVID-19 infection. Laboratory tests using these markers on the first day of hospitalization and a few days after would be useful in the clinical evaluation of disease status and progression. For would-be severe cases, a quick and aggressive administration of the potential therapeutic agents discussed would prevent or attenuate the effect of the advancing cytokine storm.”

“Recommendation Several diagnostic markers for cytokine storms indicate that they could be easily identified and promptly arrested. Rapid prophylaxis and treatment of cytokine storm by clinicians will significantly enhance success in the fight against the dreaded COVID-19 pandemic.”

“Policymakers should consider the recommendation for the off-label use of medications with potential activity against cytokine storm.”

“Original studies on the genetic and other remote causes of the defective innate immune system are needed.”

Rowaiye AB, Okpalefe OA, Onuh Adejoke O, Ogidigo JO, Hannah Oladipo O, Ogu AC, Oli AN, Olofinase S, Onyekwere O, Rabiu Abubakar A, Jahan D, Islam S, Dutta S, Haque M. Attenuating the Effects of Novel COVID-19 (SARS-CoV-2) Infection-Induced Cytokine Storm and the Implications. J Inflamm Res. 2021 Apr 16;14:1487-1510. doi: 10.2147/JIR.S301784. PMID: 33889008; PMCID: PMC8057798.

10) COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons

On May 7th, 2020 six Chinese researchers released a report warning the world of the medical realities of COVID-19, that ‘no specific therapeutic drugs or vaccines are available to treat COVID-19 patients.’ While vaccines may reduce the chances of experiencing severe symptoms with SARS-CoV-2, coronavirus vaccines do not offer immediate relief for those already infected with COVID-19.

The research suggests the use of Remdesivir, a toxic substance used in National Institutes of Health’s suggested procedures to treat COVID-19 patients12, as a viable substance to treat cytokine storm in patients. While there may be benefits to the use of Remdesivir, they are also devastating consequences to its biological toxicity.

COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons13

“The outbreak of the novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) responsible for coronavirus disease 2019 (COVID-19) has developed into an unprecedented global pandemic.”

“Clinical investigations in patients with COVID-19 has shown a strong upregulation of cytokine and interferon production in SARS-CoV2- induced pneumonia, with an associated cytokine storm syndrome.”

“Thus, the identification of existing approved therapies with proven safety profiles to treat hyperinflammation is a critical unmet need in order to reduce COVI-19 associated mortality.”

“To date, no specific therapeutic drugs or vaccines are available to treat COVID-19 patients.”

“New therapeutic interventions will likely require a long lead time for the development of approved drugs.”

“In a recent study with MERS-CoV infected patients, the combination of Remdesivir and IFNbeta revealed superior antiviral activity, compared to the effect of lopinavir and ritonavir. Treatment of these patients with oral ribavirin and subcutaneous pegylated IFN alpha-2a demonstrated significant improvement in survival, provided that adequate monitoring and assessment was available.”

“Remdesivir and IFN beta may likewise prove useful in the treatment of COVID-19, particularly since recent clinical trials have demonstrated that Remdesivir shortened the length of time in hospital intensive care for Covid-19 patients.”

“[I]t may be worthwhile to test the safety and efficacy of human and recombinant IFNs in SARS-CoV-2-infected patients, alone or in combination with other antiviral drugs”

“At present, there are no Food and Drug Administration (FDA)-approved drugs specifically indicated for the treatment of patients with COVID-19, with the exception of the recently studied Remdesivir. It was shown that Remdesivir reduced the patients’ time in ICU from fifteen days to eleven days.”

“Originally developed as a small molecule compound against Ebola virus, Remdesivir acts by inhibiting the viral RNA dependent RNA polymerase.”

“However, it is difficult to imagine how the direct antiviral properties of Remdesivir could be potently active during the immunopathogenic ARDS phase of COVID-19 disease, suggesting that other off-target effects may be attributed to the drug. Further studies, particularly amongst patient populations at earlier stages of the disease, are warranted to resolve these issues.”

“While working to prevent future outbreaks of coronavirus infections with vaccine development and new or re-purposed anti-viral medicines, it remains of utmost importance to use the knowledge at our disposal to treat those patients most at risk of dying from Covid-19-induced cytokine storms.”

Nile SH, Nile A, Qiu J, Li L, Jia X, Kai G. COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons. Cytokine Growth Factor Rev. 2020 Jun;53:66-70. doi: 10.1016/j.cytogfr.2020.05.002. Epub 2020 May 7. PMID: 32418715; PMCID: PMC7204669.

11) Follow-up studies in COVID-19 recovered patients – is it mandatory?

On August 10, 2020 a group of twelve researchers from India reported cytokine storms in COVID-19 patients

Follow-up studies in COVID-19 recovered patients – is it mandatory?14

“Reports have suggested that the SARS-CoV-2 mainly affects the people who have had any previous medical conditions related to lungs, kidney, heart and the GI tract (Meredith et al., 2020). In the lungs, the virus-mediated cytokine activation in the alveolar macrophages results in lung fibrosis and damage.”

The binding of SARS-CoV-2 to the ACE2 receptors in the heart could deviate the normal ACE2 signalling pathways consequentially leading to acute myocardial infarction (Xiong et al., 2020). This alteration in the ACE2 signalling pathway could also arise into acute systemic inflammatory responses and cytokine storm and may cause multiorgan failure or damage in the human system (Huang et al., 2020).”

The cytokine storm can cause an increase in proliferation of cardiac muscle cells and might form a fibrous cap on the fatty steak. This results in necrotic lipid core rupture, which forms blood clots resulting in myocardial infarction.”

“According to World Health Organization (WHO), the mortality rate of COVID-19 patients is 3 to 5%, and the remaining affected patients will mostly recover15. The Government officials in all countries continue to make efforts to minimize human contact by facilitating countrywide shutdowns of public places as well as various steps have been initiated to ensure the safety of the people, like social distancing and self-quarantine which limits our social interactions.”

“By knowing the possible complications of its after-effect from the recovered patients will be helpful to ascertain the future disease complications and will provide more information for the development of vaccines and drugs for these kinds of pandemics in the future. More research is required on the diagnostic and therapeutic approaches to develop vaccines and drugs”

“COVID-19 has materialized into a deadly disease affecting people worldwide. Besides the common symptoms that occur in COVID-19. It has recently uncovered into a multifaceted condition known to affect various other organs. This disease appears to be at the hub of various converging pathways. Altogether they exhibit detrimental effects on the individual who have infected with the virus.”

“The severe forms of the conditions have progressed into ARDS, septic shock, coagulation dysfunction and death, while the mild and moderate cases seem to have a positive recovery rate.”

“The maximum number of patients in the world have been recovered and discharged after infection and getting treatment. Although this seems celebratory, the major drawback of COVID-19 included is the speedy transmission capacities. In addition, the long-term effects of COVID-19 remain still unknown.”

“It needs to figure out if the virus-mediated organ damage completely improves on recovery? In order to determine the actual consequences of the condition, it is essential to maintain follow-up studies on patients, and it will help to determine diseases at initial stages and allowing medical intervention in a timely manner”

Balachandar V, Mahalaxmi I, Subramaniam M, Kaavya J, Senthil Kumar N, Laldinmawii G, Narayanasamy A, Janardhana Kumar Reddy P, Sivaprakash P, Kanchana S, Vivekanandhan G, Cho SG. Follow-up studies in COVID-19 recovered patients – is it mandatory? Sci Total Environ. 2020 Aug 10;729:139021. doi: 10.1016/j.scitotenv.2020.139021. Epub 2020 Apr 27. PMID: 32360909; PMCID: PMC7184970.


If cytokine storms are responsible for the majority of the COVID-19 deaths, the medical dictatorship has been treating the symptoms of coronavirus completely wrong. While there is evidence that the mandated experimental concoctions reduce symptoms, in many instances steroids and alternative forms of treatments have produced successful results. This would conclude that mandating vaccines are not the only method to fight back against the effects of COVID-19. It would mean we, the people, have been being lied to by the digital iatrarchy, and were subjected to participation in experimental mRNA trials. The medical elite have their claws in the flesh of the American populous, absorbing civil rights, individualism, and possibly even our health in the process. If cytokine storms are in fact responsible for the devastation that the coronavirus pandemic has ravaged upon American liberty, the medical oligarchs responsible for mandating human decision are the ones who will historically hold accountability for knowingly sending people to their deaths, over profiting over a COVID-19 vaccine.

To top it off, coronavirus concoctions are considered “leaky vaccines,” meaning the vaccines do not one hundred percent prevent infection, they only reduce the symptoms when exposed to the Spike Protein. While the live virus of SARS-CoV-2 is believed to responsible for Cytokine Storms, data shows that “Leaky Vaccines” may also provide the optimal living environment for mutations to occur, while the host remains asymptomatic. If leaky vaccines allow asymptomatic carriers to act as a host, the active virus can still exist within the body and its organs, could the presence of COVID-19 within a vaccinated individual provide more susceptibility to trigger a Cytokine Storm? Could mutations which develop inside of vaccinated hosts trigger cytokine storm when the modified virus is spread to unvaccinated individuals?

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