The Cytokine Storm & COVID-19

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Re: The Cytokine Storm & COVID-19

Post by TimGDixon »

Its about time. a year ago i identified nlrp3 as the gene responsible for acetylation of NALP3 into the complex NLRP3 which in turn secretes the inflammasome of il-1b and il-18. Good find - thanks for sharing.
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Re: The Cytokine Storm & COVID-19

Post by trader32176 »

I'm really looking for some good results
from the QM trial !
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Re: The Cytokine Storm & COVID-19

Post by curncman »

Trader great find that tells the world now that QUadramune exactly does inhibit NLRP3 which otherwise incites "Cytokine Release Syndrome". This is what Tim Dixon has been crying out loud to alert the virologists to accordingly make vaccines but I glad now its being taken seriously. QUADRAMUNE is already been found efficacious in preventing all virus stains!
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Re: The Cytokine Storm & COVID-19

Post by trader32176 »

Could cinnamon modulate the immune response in severe COVID-19? / Hops & Cinnamon Extracts

3/18/21 ... ID-19.aspx

Since the coronavirus disease 2019 (COVID-19) pandemic’s first emergence, limited progress has been made in developing effective and safe antivirals to prevent and treat infection by the pathogen responsible, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A new study recently appeared in the journal Frontiers in Plant Science that describes the potential for two common plant products to make a difference in the management of severe COVID-19.

In severe and critical COVID-19 patients, a so-called cytokine storm has been identified, characterized by exaggerated inflammation and acute respiratory distress syndrome (ARDS), often with multisystem damage and organ failure.

The inflammatory response is due to the production of high levels of reactive oxygen and nitrogen species (ROS/RNS) that establish the vicious cycle of further inflammation. The inflammatory damage that can be done to the lung alveoli, the endothelium, and the ingrowth of blood vessels has become clear.

This type of inflammation centered on the blood vessels is not confined to the damaged lungs in COVID-19, but also involves sustained inflammatory changes in the liver, brain, gut and heart, among other organs. Thus, the ability to prevent or restrict the cytokine storm and reduce the oxidative stress on these organs would be useful in preventing death and could even, perhaps, reduce the viral load by suppressing viral replication.

One such option has been dexamethasone, which reduces mortality by 30% in patients on ventilators.

The current study is a follow-up of a prior screen that involved 99 herbal extracts thought to be anti-inflammatory. It zooms in on the top two, namely, Hop (Humulus lupulus, cones) and Ceylon cinnamon (Cinnamomum verum alias C. zeylanicum, bark) extracts.

These were found to bring about steep declines in activation of a key regulator of pro-inflammatory cytokines, namely, transcription factor NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells).


Hops are seed cones containing pharmacological compounds like humulone, lupulone and xanthohumol. The extracts of these cones seem to have antiviral effects. Humulone may suppress the replication of the respiratory syncytial virus in cell culture, for instance. Xanthohumol is synergistic with interferon-alpha against the bovine viral diarrhea virus (BVDV).

Humulone is also synergistic with some antibiotics; has anti-inflammatory effects via the suppression of cyclo-oxygenase expression following exposure to tumor necrosis factor (TNF); and can inhibit Toll-like receptor 4 (TLR4) and NF-κB signaling.

Xanthohumol is anti-inflammatory following viral or lipopolysaccharide (LPS) challenge, downregulating interleukins and TNF, and could also reduce oxidative DNA damage.

Hop extract is also useful in alleviating ROS and RNS, reducing nitric oxide synthase (nNOS) activity within neurons, and lipid oxidation. It also activates the important regulatory molecule and transcription factor nuclear factor erythroid 2-related factor 2 (NRF2).

Anti-thrombotic and anti-fibrogenic effects have also been reported in animal studies and in vitro, respectively.

Cinnamon is a spice with Chinese and Ceylonian varieties. The latter is discussed here. Like hops extract, this too has anti-inflammatory activity, antagonizing TLR2 and TLR4 activation and inducing NRF2. It also inhibits angiogenesis.

What are the implications?

The researchers found that both hops and cinnamon extracts have many anti-inflammatory functions, including reducing the release of pro-inflammatory cytokines and preventing angiogenesis, blood clotting, and endothelial inflammation within blood vessels.

Their activity in triggering NRF2 expression should also reduce the ROS and RNS generation from the high level typical of inflammation. Thus, both these extracts could reduce the complications of severe COVID-19.

Testing both extracts, either alone or in combination, and particularly as a supplemental treatment to other medications, might be a promising therapeutic approach.”

Since dexamethasone is showing promising results, but has potentially serious adverse effects such as arteriosclerosis, supplementation with these extracts may prevent complications of dexamethasone therapy as well.

Patients on mechanical ventilation often have pneumonia, and hops extract could help counter this as well.

Further studies will show if these extracts are useful in protecting against SARS-CoV-2. Their common use or derivation from substances used in food indicates their safety, unless there is hypersensitivity to either of them or alcohol intolerance, which prevents the use of alcoholic extracts.

They can also be produced on a large scale and are readily available, thus proving their benefits in low-resource settings.

However, it should be noted that the individual components in each of the herbal extracts probably have a synergistic effect, making them superior to the pure substances.

More convenient formulations such as capsules or water extracts may be used to allow easier administration. The dosage remains to be determined once the current findings are confirmed, drawing on earlier studies that used these compounds to treat other inflammatory conditions.

Journal reference:

Lucas, K. et al. (2021). Cinnamon and Hop Extracts as Potential Immunomodulators for Severe COVID-19 Cases. Frontiers in Plant Science. ... 89783/full
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Re: The Cytokine Storm & COVID-19

Post by trader32176 »

Study reveals unknown immune defense system that protects the lungs from viral infections

3/18/21 ... tions.aspx

Researchers have uncovered a previously unknown arm of the immune defense system that protects the lung from lethal viral infections.

Respiratory diseases caused by viruses such as influenza A and SARS-CoV-2 cause damage not just through their own actions, but also from collateral damage as the immune system reacts to fight the infection.

A timely and proportionate response identifies viruses, isolating them in tiny vesicles called phagosomes that are then targeted for breakdown. This processalso triggers production of cytokines to alert the immune system.

Cytokine responses represent a fine balancing act that can sometimes tip over to an excessive state known as the cytokine storm. This has serious consequences for viral lung infections, as it leads to inflammation, fluid building up in the lungs and eventually death.

Given the impact of respiratory conditions, brought into sharp focus by the COVID-19 pandemic, there's a clear need to fully understand the complexities of this immune response to develop better treatments or targets for drugs that can protect against infections taking hold.

To address this teams from the Quadram Institute and universities of Liverpool, East Anglia (UEA), and Bristol have worked together to studythe immune response to influenza A virus infection in the lungs of mice. Animal models provide a way of understanding how the immune system works, and as with SARS-CoV-2, animals may be a significant reservoir for viruses that, if transferred to humans, can trigger pandemics.

Funded by the Biotechnology and Biological Sciences Research Council, they focussed on a recently characterised form of non-canonical autophagy called LC3-associated phagocytosis (LAP) that recognises pathogens as they enter cells.

Professor Tom Wileman at the Quadram Institute has worked with Dr Penny Powell and Professor Ulrike Mayer at UEA to develop a LAP-deficient mouse to study viral infection. Unique to this study, the mice were designed to retain the normal autophagy machinery, and target LAP within immune cells, so are the best available option for understanding the precise role of this newly uncovered immune defense.

Prof James Stewart at the University of Liverpool characterised the function of LAP by infecting the transgenic mice with influenza virus and studying the response to infection.

The mice were found to be much more susceptible to the virus, with it triggering a cytokine storm leading to pneumonia. The researchers showed that LAP prevented a lethal cytokine storm by supressing lung inflammation.

So where does this protection come from? Dr Yohei Yamauchi and colleagues from the University of Bristol provided the answer by looking at the cells lining the surface of the lung. There was no difference in how the virus initially binds to these cells, but they did see that non-canonical autophagy/LAP did slow the way the virus enters the cell. It may work by preventing the virus fusing with endosomes, which are the cell's way of importing materials from outside.

Non-canonical autophagy/LAP is likely to be important as a first defense against infection, where there is no immunity from previous infections, especially in the specific case of influenza and SARS-CoV-2.

" Being able to describe this novel part of the immune defense system against respiratory infections in very exciting, especially given the current pandemic. We need to assess whether the same system provides similar protection in humans, but this does point to the possibility of developing new drugs that manipulate this non‐canonical autophagy to increase resistance at the lung surface, where it is most needed."

- Tom Wileman, Professor, University of East Anglia and Quadram Institute


Quadram Institute

Journal reference:

Wang, Y., et al. (2021) Non‐canonical autophagy functions of ATG16L1 in epithelial cells limit lethal infection by influenza A virus. The EMBO Journal.
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Re: The Cytokine Storm & COVID-19

Post by trader32176 »

SARS-CoV-2 spike stimulates hyperinflammation via Toll-like receptor 2

3/19/21 ... tor-2.aspx

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been ravaging the world for a year and a half, causing well over 2.6 million deaths.

A new study, released on the bioRxiv* preprint server, describes the mechanism of inflammation in severe COVID-19, besides revealing a potential new therapeutic target to modulate the severity of COVID-19.

The significant percentage of severe and critical disease following infection by the virus has been a cause of great concern. It is associated with dysregulated inflammation, but the pathogenesis remains unclear.
The spike protein

The current study demonstrates the inflammatory potential of the spike protein of the virus as being key to the cytokine storm. The spike protein not only forms the characteristic corona of the virus, but mediates receptor binding to the host cell angiotensin-converting enzyme 2 (ACE2) receptor on alveolar epithelial cells.

This is followed by viral entry and productive infection, with the replication of the genome and the transcription of genomic and subgenomic ribonucleic acid (RNA). The eventual outcome is the death of the infected cells.

Inflammatory injury in COVID-19

The lung tissue is further injured by the inflammatory infiltrate of macrophages, monocytes and neutrophils, all of which are responding to the expression or presence of viral proteins in the host cell. They are also activated by the products of dying cells.

This is called innate immunity and is essential to provide protection against the virus. In severe COVID-19, the excessive release of cytokines and chemokines produces deleterious effects on the host tissue, particularly in the lung and the endothelium of the vasculature.

Higher levels of inflammatory interleukins (IL) such as IL-2, IL-6, IL-8, the tumor necrosis factor (TNF), and chemokines like the monocyte chemotactic proteins (MCP1), with the potent growth factor granulocyte monocyte colony-stimulating factor (GMCSF) have been detected in the blood of COVID-19 patients.

Both IL-6 and TNF-alpha have been correlated with morbidity and mortality in COVID-19.

Pathway of inflammatory damage

The pattern of innate inflammation begins with the recognition of pathogen-associated molecular patterns (PAMPs). This is in response to pattern recognition receptors (PRRs), such as Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-I like receptors (RLRs).

The presence of viral RNA is detected by RNA sensing receptors, namely, TLR7, RIG-I, and MDA5. Following activation, PRRs set off multiple signaling molecules that mediate the activation of transcription factors for genes involved in immunity and inflammation. These include NF-kB, AP1, and IRF3.

IRF3 and NF-kB induce interferon (IFN) responses, both alpha and beta interferons, which are fundamental to antiviral responses, both innate and adaptive.

Earlier studies have shown that both dendritic cells and macrophages in the innate immune pathway produce inflammatory cytokines and chemokines in response to SARS-CoV infection. However, type I IFNs were not seen to be produced. This pattern of high inflammatory cytokines but low type I IFN is reproduced in COVID-19 patients with severe disease.

SARS-CoV-2 spike causes inflammation of innate immune cells

The current study demonstrates that macrophages stimulated with the spike, as well as with either of its subunits, the S1 or S2, produce IL-6, TNFa, and IL-1b. S2 is more potent in this respect.

Macrophages are key to the hyperinflammatory response in COVID-19. They produce signaling molecules that recruit T cells and other immune cells to the site of inflammation, further worsening the damage.

Chemokines like CXCL1, CXCL2, and CCL2 were released by the macrophages in response to S1 and S2, in a dose-dependent fashion. Other viral proteins failed to do so, and if the spike S2 was denatured by heat, no inflammatory response occurred either.

These results were confirmed by stimulating human peripheral blood mononuclear cells (hPBMC) with S2, when cytokines and chemokines were potently induced.

In lieu of mouse macrophages, that lack the human ACE2 receptor, the researchers challenged mouse bone marrow-derived macrophages (mBMDMs) with S1 and S2. Again, the same response was found, but no type I or type II IFN response.

Epithelial inflammatory response to spike

The virus also infects epithelium of the lungs, kidneys, gut and the vascular endothelium. Both S1 and S2 proteins resulted in inflammation in a delayed fashion, with the highest level being at 24 hours after stimulation. This was followed by gamma-interferon induction, but not type I IFN.

The presence of the spike within the cytosol did not, however, induce inflammation in epithelial cells.

Spike-expressing epithelial cells trigger macrophage inflammation

The results also showed that cytosolic spike within epithelial cells, but not kidney cells, induced inflammatory responses in co-cultured innate immune cells.

Spike activates the NF-kB pathway

The researchers observed that spike stimulation led to the activation of the NF-kB pathway, which is, along with MAPK, STAT3, and AKT, one of the signaling pathways concerned with activating transcription factors for inflammatory genes. STAT3 activation was also seen, but not MAPK or AKT.

TLR2-dependent NF-kB activation was observed. Typically, TLRs are triggered as a result of recognizing PAMPs on the cell surface or within the endosome, and this activation occurs via the adapter protein MyD88. The researchers found that spike protein activated the NF-kB pathway via this recognized pathway.

Specifically, TLR2, which is known to recognize lipoproteins, was identified to be the receptor responsible. In TLR2 knockout mice, intraperitoneal challenge with S1 or S2 resulted in increased levels of inflammatory cytokines IL-6, IL-1b, and TNFa.

Mechanism of activation of innate immune cells

The researchers suggest that innate immune cells like monocytes and macrophages recognize the spike protein at the cell surface via their TLR2 receptors, as described above. Secondly, spike-expressing epithelial cells can activate macrophages in their close vicinity.

Thirdly, epithelial cells can be activated by extracellular spike protein, inducing inflammatory signaling molecules, though not so potent as innate immune cells. However, this phenomenon can occur in the SARS-CoV2-infected lungs, which are the primary site of disease in COVID-19 patients.

What are the implications?

" These data suggest that TLR2 is the immune sensor for SARS-CoV-2 S protein, which potentially triggers inflammatory responses through the activation of the NF-kB pathway.”

The spike protein is thus a powerful PAMP that induces hyperinflammation via this pathway.

Many COVID-19 vaccines have been developed to advanced clinical trial stages within a short period. However, most of them use the spike antigen, which may be important in view of the above findings.

Secondly, the emergence of new variants with extensive mutations in the spike protein may lead to more severe disease, possibly resistant to existing antibodies and to those elicited by current vaccines. This makes it imperative to develop effective therapies against the virus.

The study suggests TLR2 or its downstream adapters as ideal therapeutic targets to reduce the level of inflammation, and its consequences on the host, in COVID-19.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

Khan, S. et al. (2021). SARS-CoV-2 spike protein induces inflammation via TLR2-dependent activation of the NF-κB pathway. bioRxiv preprint. doi:, ... 6.435700v1
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Re: The Cytokine Storm & COVID-19

Post by trader32176 »

Newly identified pathway controls dangerous overreactions in the body's immune system

3/26/21 ... ystem.aspx

Scientists at Sinai Health say they have discovered a new pathway that controls dangerous overreactions in a body's immune system, including deadly forms of hyper-inflammation.

In new findings out today in the journal Science, researchers at the Lunenfeld-Tanenbaum Research Institute (LTRI) detail how a protein known as WAVE2, a protein expressed in all immune cells, plays a critical role in maintaining immune system balance.

As part of the research, scientists knocked out, or turned off, WAVE2 in a subset of immune cells in mice, which led to severe autoimmunity and inflammation, as well as an inability to mount an immune response to a viral infection.

The study's senior author, Dr. Kathy Siminovitch, said they also found that another protein, known as mTOR, became overly active in the absence of WAVE2, putting the immune system into overdrive and leading to immune cell exhaustion.

" Much like Goldilocks, a proper immune response requires such a delicate balance. You have to get it just right. By developing a mouse strain in which T cells, key players in immunity, lack WAVE2, we have shown that this protein is absolutely required for balanced immune responses."

- Dr Kathy Siminovitch, Senior Investigator and Canada Research Chair in Mechanisms Regulating Immunologic Disease, Lunenfeld-Tanenbaum Research Institute

How to keep the immune system from going into overdrive has been a key question for medical experts as they continue to grapple with the devastating effects of COVID-19 pandemic, particularly on the elderly population.

Patients over the age of 65 are at a higher risk of developing severe COVID-19, partly due to a phenomenon called "cytokine storm" where the immune system overacts and damages organs.

"The pandemic has starkly illuminated the critical importance of immune balance and the severe consequences of disrupting such balance," said Siminovitch. "It has also highlighted the importance of fundamental research, which has taken us where we are today in understanding the virus and having treatment and prevention strategies in hand."

For years, Dr. Siminovitch has been exploring the genetic and molecular mechanisms that regulate and maintain balance across the immune system. In previous work, she helped trace the complex molecular steps that turn a rare gene mutation into Wiskott-Aldrich syndrome, which impairs the immune system of boys, and can lead to death at a very young age.

Dr. Siminovitch said they would like to expand their research to look at how the WAVE2-mTOR pathway may contribute to specific autoimmune, inflammatory and other conditions, such as Alzheimer's disease.

"Understanding how to achieve this kind of control in immunity is really important," said Dr. Siminovitch. "This research opens the door to new ways of restoring that balance through the development of new therapeutics that target the WAVE2- mTOR pathway."


Lunenfeld-Tanenbaum Research Institute

Journal reference:

Liu, M., et al. (2021) WAVE2 suppresses mTOR activation to maintain T cell homeostasis and prevent autoimmunity. Science. doi.org10.1126/science.aaz4544.
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Re: The Cytokine Storm & COVID-19

Post by trader32176 »

Israel scientists cure 100% of covid patients with new therapy that mitigates cytokine storm

2/9/21 ... storm.html

Israeli scientists have developed a promising new immune therapy that cured 100 percent of covid patients in three to five days. The therapy helps mitigate the cytokine storm that is sometimes observed in covid patients. The Tel Aviv Sourasky Medical Center has developed a drug called EXO-CD24, which functions as an experimental inhaled medication. In the Phase 1 clinical trial, the medication cured all thirty cases of moderate to severe covid-19 infection. The medication is inhaled for a few minutes, once a day, for five days.

The immune therapy mitigates the overproduction of cytokines, restoring inter-cellular communication, and helping the person’s immune system detect and combat replicating viruses. Because it is delivered precisely to the lungs, there are no systemic side effects, as often observed with oral or injected drugs.

New immune therapy medication cures all covid patients in phase 1 clinical study

Around 5-7 percent of covid patients suffer from a cytokine storm. This is when the immune system overreacts and starts attacking healthy cells in the lungs. The inhaled medication uses exosomes (vesicles) that are typically released from cell membranes. These exosomes are released for the purpose of inter-cellular communication. The medication enriches the exosomes with 24CD protein. In a healthy immune system, this protein is expressed on the surface of the cell and helps regulate the immune system. The medication supplies the lungs with this critical protein for inter-cellular communication, to help modulate a healthy immune response. The people who experience complications from respiratory infection are lacking critical surface surveillance proteins that help the immune system communicate and detect viral threats.

The hospital in charge of the study, reports: “To date, the preparation has been tried with great success on 30 severe patients, in 29 of whom the medical condition improved within two to three days and most of them were discharged home within three to five days. The 30th patient also recovered but after a longer time.”

The drug can be produced very quickly and distributed at a very low cost to hospitals and pharmacies around the world. “Even if the vaccines perform their function, and even if no new mutations are produced then still in one way or another the corona will remain with us,” said Prof. Nadir Arber, director of the medical center’s Integrated Cancer Prevention Center. “To this end, we have developed a unique drug, EXO-CD24.” The research is built upon the work of Dr. Shiran Shapira who has been researching the CD24 protein for over two decades.

Finding the underlying causes of damaged immune systems is key to overcoming infectious disease

No matter the level of masking, no matter how many vaccines are pumped into people’s arms; populations continue to suffer from respiratory illness, whether its covid-19, pneumonia, one of many hospital-acquired infections, or any other influenza mutation or coronavirus variant. The demand for antiviral drugs and immune therapy is high, and will remain high well into the future as malnourished, over-vaccinated populations seek medical help for their autoimmune issues, inflammatory conditions, strained lungs and compromised cellular terrain.

Another protein that is an important facet of the human immune system is mannose binding lectins (MBLs). A subset of human populations is born deficient in MBLs, a surface surveillance protein that helps the immune system detect invading pathogens. MBLs are unique because they can bind to the surface of microbes and activate the complement system in an antibody. Deficiency in MBLs occurs when there is a three single point mutation in exon 1 of the MBL-2 gene. MBLs bind with sugars including N-acetyl-D-glucosamine, mannose, N-acetyl-mannosamine, fucose and glucose.

This sugar-binding process allows the protein to interact with many different kinds of viruses, bacteria, yeasts, fungi and protozoa cloaked with such sugars. Deficiency in MBLs is linked to chronic obstructive pulmonary disease and complications from respiratory syncytial virus (RSV), and other respiratory distress. Oxidative stress decreases functional airway mannose binding lectin in COPD. Mitigating oxidative stress is also important for healthy function of lung cells and surface proteins. In short, the surface surveillance proteins are an important factor in how people recover from infectious disease. Finding the underlying causes of damaged immune systems is key to overcoming infectious disease.
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Re: The Cytokine Storm & COVID-19

Post by trader32176 »

High antibody and inflammatory mediator levels may predict severe COVID-19

4/15/21 ... ID-19.aspx

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly the world over. To date, over 138.3 million cases have been confirmed, and over 2.9 million deaths reported.

A new study released on the bioRxiv* preprint server reports on biomarkers could help predict the progression of the viral illness to dangerous levels early enough to enable timely intervention.

Prediction of COVID-19 progression

The mostly asymptomatic nature of COVID-19, coupled with the high infectivity of the virus, drives its spread. In a significant minority of cases, the disease progresses to become serious or critical, requiring intensive medical care.

In such cases, the patient rapidly deteriorates and develops severe inflammatory lung disease, resulting in acute respiratory distress syndrome (ARDS). This is often accompanied by other multi-organ dysfunction and sepsis.

The risk of severe disease is much higher in older adults over 80 years of age and people with comorbidities such as hypertension, diabetes, or obesity. The outcome may be an efficient viral clearance or a hyperintense inflammatory response that leads to severe lung damage, organ failure and chronic sequelae, a prolonged illness or death.

The current study considers clinical, virological and immunological markers in patients hospitalized with COVID-19, in order to identify mild, moderate and severe disease. These features were followed up at the time of diagnosis, and at various points until six months from the onset of confirmed infection.

Study details

The study included 24 hospitalized patients, of whom over 80% were males, the median age being 61 years. Half of them fulfilled the criteria for obesity, with a body mass index (BMI) over 30. More than 40% had hypertension.

The median duration of hospital stay was eight days. One in five required admissions to the intensive care unit (ICU). A third was diagnosed as having severe COVID-19.

There were 92 nasopharyngeal swab samples yielding viral ribonucleic acid (RNA), taken at different times. That is, 24 came from admission polymerase chain reaction testing; 18 were from day 3, 13 from day 5, 5 at day 15, and 16 at one month. Finally, 16 were collected at three months.

Virus tests

Almost all patients tested positive at baseline, with a median viral load of >2,000 copies/10,000 cells. One patient was negative, probably due to poor sampling. With decreasing viral loads over time, 80% of patients were negative at one month from diagnosis.

The virus persisted in five patients, as shown by positive tests at one and three months. All five had severe COVID-19 along with underlying cardiovascular disease, hypertension or diabetes.

Viral loads

In the acute phase, patients with severe disease showed a slight decrease in viral load over the first six days, becoming significant only after this period. Conversely, there was an early and marked reduction seen in patients with the mild or moderate illness.

Antibody levels

There were over a hundred serum samples available for antibody testing, following almost the same pattern of the collection as the nasopharyngeal swabs. The anti-SARS-CoV-2 IgA levels were variable at baseline, increasing progressively up to day 6 and then declining until the sixth month. The highest levels at baseline and later were in patients with severe COVID-19.

The same pattern was visible for IgM and for IgG. The rise in IgG levels was much slower until day six, but then decreased gradually to very low titers at month 6. However, at this time point, the levels were fourfold higher than in non-infected controls, at ~16 vs. 4.5 μg/mL, respectively.

Cytokine levels

The median levels for nine cytokines, as measured in 18 patients, including TNF-α, IL-6, IL-8, IL-1β, and MIP-1α, showed variations between inflammatory and other cytokines.

Higher levels of IL-6, IL-8, and MIP-1β at baseline were associated with severe disease. High levels persisted for inflammatory markers like IL-6, IL-8, IP-10, TNF-α and sCD25 throughout the study period in severe COVID-19 compared to mild or moderately ill patients.

However, for MIP-1β, IL-1β, MIP-1α and IFN-γ, the levels of some of these were higher at one and three months among those with mild or moderate disease vs. those with severe disease.

At 6 months, no difference was observable among the different groups.

High antibody and cytokine levels were found in patients with ARDS vs. those without this complication, as well as mechanical ventilation and ICU admission. Viral load at baseline showed no such correlation.

What are the implications?

The persistence of viral RNA in five patients, all of whom had either severe COVID-19 or underlying chronic conditions, or both, indicate the need to understand the clinical importance of the presence of the virus in different body compartments, whether plasma, gut or upper airway.

If this is known, it could help to keep an alert eye on acutely infected patients as well as follow them up once acute symptoms remit.

The results show that the following markers are related to severe illness: high titers of specific IgA, IgM, IgG and high levels of the cytokines IL-6, IL-8 and MIP-1β, at the time of admission; and prolonged presence of viral RNA in the upper airway in the first few days after diagnosis.

The rapid decline in IgA and IgM antibodies following the acute infection phase is shared by IgG, but at a slower pace. However, at month 6, the titers of specific IgG antibodies remained higher compared to naïve subjects, indicating durable immunity.

This echoes other studies which show persistent IgG antibodies at up to eight months after the onset of infection. The correlation of such antibodies with neutralizing activity is unknown and remains an urgent research question.

The role played by hyperactive inflammation in the damage caused by the infection is underlined by the high levels of inflammatory cytokines observed in this study. The individual parts for which each of these is responsible remains to be elucidated.

This small study presents interesting findings which should be validated and followed up, to identify and quantify the predictive value of these markers of severe COVID-19 well before clinical deterioration sets in.

*Important Notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:

Codina, H. et al. (2021). Elevated anti-SARS-CoV-2 antibodies and IL-6, IL-8, MIP-1β, early predictors of severe COVID-19. bioRxiv preprint. doi:, ... 3.439586v1
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Re: The Cytokine Storm & COVID-19

Post by trader32176 »

Researchers discover that Kefir (fermented yogurt) can halt cytokine storms observed during SARS-CoV-2 infections

5/3/21 ... ction.html

One of the most important areas of scientific research for combating SARS-CoV-2 involves understanding cytokines and mitigating cytokine storm. Cytokines are cell signaling molecules that facilitate immune responses. These molecules communicate between cells to stimulate the movement of immune responsive cells toward sites of inflammation and infection. Israeli scientists have found that yogurt (kefir) can halt the cytokine storm that affects some COVID-19 patients. The yogurt changes the individual’s microbiome, strengthening the commensal species of bacteria in the gut. This strengthening of the microbiome allows gut microbes to readily identify pathogenic threats and modulate communication between cells, so the immune responsive cells can more efficiently respond to infections, without over-reacting.

Researchers at the Ben-Gurion University of the Negev have identified molecules in kefir that regulate inflammation in the body and help cells communicate more effectively. The research, conducted by PhD student Orit Malka and Prof. Raz Jelinek, was published in Microbiome. These probiotics interfere with the bacterial biofilms that contribute to disease progression. They effectively reduce replication of vibrio cholera, the causative agent behind cholera. These probiotic molecules work by blocking communication between cells.

Mitigating cytokine storm is essential for saving lives impacted by bio-weaponry

SARS-CoV-2 is engineered to target the ACE2 receptor on human lung cells. If the infection is not properly detected by the innate surveillance immune proteins on the surface of lung cells, the virus may evade detection and replicate unabated. This can set off a cytokine storm that causes a hyperinflammatory immune response that destroys healthy lung cells. This is the first reason why covid-19 patients need intensive care. Immune compromising drugs like antibiotics and proton pump inhibitors (antacids) can weaken the microbiome, distorting cytokine communication between immune responsive cells.

The cytokine storm is observed in a small minority of patients, but it can lead to further issues that threaten the person’s survival. The next reason why covid-19 patients need intensive care involves the liver’s response to these hyper-inflammatory reactions. The liver may produce an influx of proteins to fight the infection that the humoral immune response failed to control. If too many liver proteins are allocated, they can coagulate the blood, clog blood vessels, and deprive patients of oxygen and nutrients. If the process is not abated, it can lead to multi-organ failure, acute lung injury, and cardiovascular events.

Similar over-reactive immune responses are observed in people who are vaccinated for SARS-CoV-2. Some vaccinated individuals experience blood clots and cardiovascular events because the vaccine induces a hyper-inflammatory response, causing an overproduction of B-cells that attack the body’s own platelets and clotting factor proteins. Further studies should investigate the role that the vaccines play in altering the gut microbiome and causing further problems with cytokines and cellular communication.

Inflammation identified as determining factor behind cytokine storm

The Lewis Katz School of Medicine and Temple University Hospital published an important report on early identification of cytokine storm in covid-19 patients. The report, published in the Annals of the Rheumatic Diseases, is the first to identify specific criteria that can be used in clinical practice to predict cytokine storm before it occurs. The research group analyzed data on 513 COVID-19 patients hospitalized at Temple University Hospital, of which sixty-four developed cytokine storm. The most important predictive factors included inflammation, cell death, tissue damage, and electrolyte imbalance.

These indicators suggest that underlying inflammation at the cellular level is one of the greatest risk factors for cytokine storm and subsequent mortality in covid-19. The good news is that kefir and other probiotics address this issue, and there are many known antioxidants, flavonoids, and nutrients that can reduce inflammation throughout the body, setting the body up for success against coronavirus and other infections.
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