Category Archives: CYTOKINE STORM

Autoimmunity: Another reason why VACCINE is safer than INFECTION.

There is growing evidence that self-attacking ‘autoantibodies’ could be the key to understanding some of the worst cases of COVID-19.

This might explain why lung damage and other organ damage sometimes continues to worsen AFTER the body seems to have cleared the SARS-CoV-2 virus. And it could explain why some individuals fail to mount an adequate immune response early in the disease.

With respect to the later, in September 2020 researchers at the Rockefeller University reported that > 10% of 987 patients with severe COVID-19 infection had antibodies that blocked type 1 interferon molecules, an essential part of the innate immune system.

Other researchers have screened patients with varying severity of COVID-19 and found higher prevalence of autoantibodies against the immune system in infected individuals compared to uninfected controls.

Yet another study found that some infected individuals had autoantibodies against proteins in their blood vessels, heart and brain.

Many patients with severe COVID suffer from life threatening blood clots. Phospholipids play a major role in controlling blood clotting. 52% of 172 people hospitalzied with COVID 19 were found to have anti-phospholipid antibodies.

Annexin A2 is a human protein that protects the integrity of small blood vessels in the lung. Researchers have found a significantly higher average level of anti-annexin A2 antibodies in people who died of COVID-19 compared to patients with less severe illness.

So far it is unclear whether the virus caused these antibodies or whether these unlucky individuals had higher than normal amounts of auto-antibodies prior to infection.

A paper published in the immunology literature just yesterday might shed some light on this issue as well as on the topic of LONG COVID.

We sought to determine whether immune reactivity occurs between anti-SARS-CoV-2 protein antibodies and human tissue antigens, and whether molecular mimicry between COVID-19 viral proteins and human tissues could be the cause.

In other words, they tested antibodies against the SARS-CoV-2 virus to see whether they reacted against various kinds of human tissue. Here is what they found.

We found that SARS-CoV-2 antibodies had reactions with 28 out of 55 tissue antigens, representing a diversity of tissue groups that included barrier proteins, gastrointestinal, thyroid and neural tissues, and more.

This extensive immune cross-reactivity between SARS-CoV-2 antibodies and different antigen groups may play a role in the multi-system disease process of COVID-19, influence the severity of the disease, precipitate the onset of autoimmunity in susceptible subgroups, and potentially exacerbate autoimmunity in subjects that have pre-existing autoimmune diseases.

You can read the full study here: https://www.frontiersin.org/articles/10.3389/fimmu.2020.617089/full

Cross reactivity between antibodies against COVID-19 virus and human tissue was found for every major organ system in the human body.

The concept of “molecular mimicry” has been well described in auto-immunity for many years. This occurs when a portion of a foreign protein (on for example a virus or bacterium) is identical to a portion of a protein found in human tissue. When the immune system responds to invasion by a virus or bacteria it creates antibodies to various proteins on the invader. But in so doing the anti-bodies can react against human tissue that shares a small common string of amino acids (referred to as an epitope).

A famous example of molecular mimicry occurs with Rheumatic Heart Disease in which antibodies against the bacteria responsible for Strep Throat cross react with heart tissue causing destruction of heart valve tissue and a resultant leaky heart valve. In this situation cross reaction can also occur with tissue in joints resulting in arthritis, another hallmark of rheumatic fever. These were serious complications of Strep Throat before Penicillin became widely available.

So far we know that sicker COVID-19 patients demonstrate antibodies against multiple types of human tissue.

We also know that antibodies that react against various portions of the virus can also react against human tissue.

Finally we know that multi-organ failure is an inflammatory response wherein the immune system, rather than the virus, causes organ failure.

It would be a reasonable conclusion that auto-immunity can acutely contribute to cytokine and bradykinin storm.

It would also be a reasonable conclusion that auto-immunity contributes to LONG COVID.

So why would that make an mRNA vaccine safer?

The mRNA vaccine results in antibodies against one part of the virus (one epitope, the spike protein).

But infection results in antibodies against MULTIPLE PARTS OF THE VIRUS (multiple epitopes). Because multiple antigens or epitopes are involved in the immune response to infection, it increases the probability that cross reaction with multiple human tissues can result.

From an autoimmune perspective, the mRNA vaccine is much safer.

Obviously, given the fact that over 400,000 deaths have resulted in the US from this infection and no deaths have been attributed to the vaccine, the vaccine appears to be much safer than infection. Both the Pfizer and Moderna vaccine have decreased the risk of symptomatic infection by 95%. Severe symptomatic infection can lead to death. Even asymptomatic infection can cause LONG COVID. The risk-benefit analysis overwhelmingly favors the vaccine.

For a deeper dive into auto-immunity and COVID-19 here are a few more references:

High frequency of cerebrospinal fluid autoantibodies in COVID-19 patients with neurological symptoms

Autoantibodies against type I IFNs in patients with life-threatening COVID-

Diverse functional autoantibodies in patients with COVID-19

Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19

 Association between anti-interferon-alpha autoantibodies and COVID-19 in systemic lupus erythematosus

Autoantibodies related to systemic autoimmune rheumatic diseases in severely ill patients with COVID-19

 IgM autoantibodies recognizing ACE2 are associated with severe COVID-19

Is the association between IgG anti‐cardiolipin autoantibodies and COVID‐19 severity related to the lung injury or to the SARS‐CoV‐2 infection?

Do cross-reactive antibodies cause neuropathology in COVID-19?

Immunoserologic detection and diagnostic relevance of cross-reactive autoantibodies in coronavirus disease 2019 patients

Anticardiolipin IgG Autoantibody Level Is an Independent Risk Factor for COVID‐19 Severity

Rheumatic manifestations of COVID-19: a systematic review and meta-analysis

The immunology of multisystem inflammatory syndrome in children with COVID-19

Clinical, Serological, and Histopathological Similarities Between Severe COVID-19 and Acute Exacerbation of Connective Tissue Disease-Associated 

In the context of the COVID 19 pandemic I will close with the usual summary.

  1. Avoid alcohol consumption (alcohol wreaks havoc with your immunity)
  2. Get plenty of sleep (without adequate sleep your immune system does not work well )
  3. Follow good sleep habits
  4. Exercise, especially out of doors in a green space, supports the immune system
  5. Get some sunshine and make sure you have adequate Vitamin D levels. Supplement with Vitamin D3 to get your levels above 30 ng/ml. (read this Open Letter)
  6. Eat an anti-inflammatory diet rich in micronutrients.
  7. Practice stress reduction like meditation and yoga which improves the immune system
  8. Eliminate sugar-added foods and beverages from your diet. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
  10. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

COVID 19 Immune Response, How does it fail?

Dr. Akiko Iwasaki, an immunologist at Yale, has led an amazing research team from the start of this pandemic, analyzing the immune response of patients sick with COVID 19. She has co-authored a review of the immune response to be published in the January edition of Scientific American.

Iwasaki A, Wong P.  The immune havoc of COVID-19.  Scientific American, January 2021, 35-41.

Here is the link.

http://The Immune Havoc of COVID-19 – Scientific American

Before reading that article, a good place for a lay person to start would be her 8 minute youtube video, Immunology 101.

After watching that video and reading the Scientific American article, if you want a deeper dive into some of her team’s research, watch this video (28 minutes).

The Scientific American article discusses many of the unique characteristics of SARS CoV-2 compared to two previous corona viruses SARS CoV-1 and MERS. SARS CoV-2 which causes the illness called COVID-19, evades the human immune system in many ways. Those who become seriously ill, requiring ICU care, seem to suffer a time lag in their immune response compared to those who suffer less severe illness. In addition, the T-cell response in sicker patients is subdued and inadequate to clear the virus. Finally, a hyper-inflammatory response is present in most who succumb to the illness. Dr. Iwasaki discusses how the Cytokine storm of COVID-19 differs significantly from that seen with other viral infections and likely includes a new phenomenon referred to as a Bradykinin Storm which involves another major component of the immune system. There may even be an auto-immune component to this disease in some or many patients.

Early in the pandemic, physicians did detect elevated cytokines in patients, but the amount of these proteins and the subsequent inflammatory state they evoked differed from that of a classic cytokine storm.

We observed high levels of IL-5 and IL-17,cytokines not classically associated with antiviral immune activity. Instead these cytokines initiate a seemingly misguided
response—one better suited for infections by parasites and fungi.
We have yet to understand whether this response causes damage
to tissue or just diverts resources the body needs to fight the virus.

In the second video linked above Dr. Iwasaki describes how men and women demonstrate different immune responses with a higher fatality rate observed among men.

Much has been learned but much remains to be discovered as this pandemic continues to unfold.

There are a few clear facts emerging from multiple studies and observations.

Masks and social distancing work. Masks protect both the wearer and those around the wearer.

Most transmission occurs by droplets and aerosol (emitted from the nose and mouth).

Six feet of distancing is helpful but does not guarantee protection. Cases of transmission in restaurants via air flow from HVAC units have been described in which the infected person transmitting disease is far removed from the people becoming infected. (aerosol spread). Droplets and aerosol studies have demonstrated that coughing and sneezing can project infectious particles up to 26 feet.

The most dangerous circumstances for transmission include indoor confined spaces, with multiple people interacting for long periods of time (restaurants, bars, meeting rooms, parties, social gatherings).

Ventilation and air turnover are important factors.

This virus is unique in that higher viral loads and transmissibility occur BEFORE ONSET OF SYMPTOMS, rendering this virus more dangerous than previous pandemics. This can occur in patients who later develop symptoms or in people who carry the virus without ever developing any symptoms.

Some estimate that as much as 50% of transmission occurs from people exhibiting no symptoms.

Finally, “herd immunity” for infectious disease has never been achieved by reaching a critical number of infected people. “Herd immunity” has only been achieved in the past with vaccination programs. Herd immunity does not mean that disease transmission ceases, it means that transmission rates are very low.

What is herd immunity?

When most of a population is immune to an infectious disease, this provides indirect protection—or herd immunity (also called herd protection)—to those who are not immune to the disease.

For example, if 80% of a population is immune to a virus, four out of every five people who encounter someone with the disease won’t get sick (and won’t spread the disease any further). In this way, the spread of infectious diseases is kept under control. Depending how contagious an infection is, usually 50% to 90% of a population needs immunity to achieve herd immunity.

Most experts estimate that vaccination of at least 70% of the population will be required to reach some degree of herd immunity for COVID-19.

Here is a 2 minute discussion of herd immunity from Johns Hopkins before the Pfizer-BioNtech and Moderna vaccines were given Emergency Use Authorization by the FDA.

In the context of the COVID 19 pandemic I will close with the usual summary.

  1. Avoid alcohol consumption (alcohol wreaks havoc with your immunity)
  2. Get plenty of sleep (without adequate sleep your immune system does not work well )
  3. Follow good sleep habits
  4. Exercise, especially out of doors in a green space, supports the immune system
  5. Get some sunshine and make sure you have adequate Vitamin D levels.
  6. Eat an anti-inflammatory diet rich in micronutrients.
  7. Practice stress reduction like meditation and yoga which improves the immune system
  8. Eliminate sugar-added foods and beverages from your diet. These increase inflammation, cause metabolic dysfunction, and suppress immunity.
  9. Eliminate refined-inflammatory “vegetable oils” from your diet, instead eat healthy fat.
  10. Clean up your home environment and minimize your family’s exposure to environmental toxins by following recommendations at EWG.org with regards to household products, personal care products, and organic foods. (https://www.ewg.org/)

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

COVID-19: ARDS, CYTOKINE STORM, and GLUTATHIONE

My good friend Dr. Deborah Gordon recently sent me a terrific article on an Integrative Medicine Approach to Covid-19. It confirmed much of what I have discussed about COVID-19 and provides 383 scientific references (many of which were cited in my previous posts). Thank you Dr. Deborah!

In my last post I promised to write about glutathione and cytokine storm.

Cytokines are proteins made by our immune system. When our body suffers an infection, cytokines act as essential signaling proteins that produce a defensive inflammatory response. In a cytokine storm the usual regulatory process that helps resolve inflammation becomes disturbed and self destruction can occur.

With COVID-19 this can happen in any organ of the body but frequently starts in the lungs, resulting in ARDS (Acute Respiratory Distress Syndrome).

In most clinical contexts the mortality rate of ARDS is 40-45%. In the context of COVID-19 it is 80-90 % lethal in most clinical reports (twice the usual mortality rate for ARDS). However, the ICU doctors in the Northwell Hospital system in NYC have been using NAC (n-Acetylcysteine).

While using NAC as part of their treatment protocol of COVID-19 associated ARDS, they are getting 50% of patients off the ventilator with a significant reduction in mortality rates compared to previous reports (personal communication with a Northwell physician and also mentioned in the Review Article cited above.)

This drug (also available as a dietary supplement) has been used for decades to treat acetaminophen (APAP) overdose (Tylenol brand name, also called paracetamol in Europe). If not treated early APAP overdose commonly causes death from liver failure.

Chronic acetaminophen toxicity is the most common cause of liver failure leading to liver transplant in the US.

How does this treatment  with NAC work in the setting of APAP overdose?

“When paracetamol is taken in large quantities, a minor metabolite called N-acetyl-p-benzoquinone imine (NAPQI) accumulates within the body. It is normally conjugated by glutathione, but when taken in excess, the body’s glutathione reserves are not sufficient to deactivate the toxic NAPQI. This metabolite is then free to react with key hepatic enzymes, thereby damaging liver cells. This may lead to severe liver damage and even death by acute liver failure.”

NAC (n-acetylcysteine) provides cysteine, one of the three amino acids that make up glutathione.

“glutathione synthesis is primarily controlled by the cellular level of the amino acid cysteine, the availability of which is the rate-limiting step.”

So by providing a source of cysteine, the body produces more glutathione which can detoxify the liver damaging metabolites of APAP.

Glutathione is our MASTER ANTI-OXIDANT. Since a cytokine storm involves an overwhelming amount of oxidative stress, glutathione is obviously important.

Clinical research in the 1990s established that the lungs of patients with ARDS are very deficient in glutathione.

A profound 20 fold reduction was confirmed in this study.

“Glutathione is a tripeptide that is able to react with and effectively neutralize oxidants, such as hydrogen peroxide. The present study found that the alveolar epithelial lining fluid of patients with ARDS was deficient in total glutathione compared with that of normal subjects (31.5 ± 8.4 versus 651.0 ± 103.1 µM, p = 0.0001) and patients with cardiogenic pulmonary edema (31.5 ± 8.4 versus 154.1 ± 52.4 µM, p = 0.001). In addition, a greater percentage of total glutathione was in the oxidized form in patients with ARDS compared with normal subjects (30.6 ± 6.1 versus 6.4 ± 2.9%, p = 0.03). This deficiency of reduced glutathione in the alveolar fluid may predispose these patients to enhanced lung cell injury.

Subsequent studies of humans with ARDS on ventilators showed clinical benefit by increasing glutathione levels with NAC.

“In our controlled clinical trials with NAC we found that patients with ARDS have depressed plasma and red cell glutathione concentrations, that these levels are substantially increased by therapy with intravenous NAC and there are measurable clinical responses to treatment with regard to increased oxygen delivery, improved lung compliance and resolution of pulmonary edema.”

Despite these findings decades ago, the use of NAC for ARDS has not been widely adopted. But it would make sense to employ this inexpensive medication, widely used for APAP overdose, for ARDS and in particular for cytokine storm caused by COVID-19.

Oxidative stress decreases glutathione levels and if these levels reach a critically  low level in tissues, organ damage can ensue rapidly. Cytokine storm is the extreme example.

Chronic alcohol abuse also decreases protective glutathione levels in the lung.

In my recent posts on COVID-19 I have pointed out that alcohol (even 2 drinks) suppresses the immune system for at least a few days. Alcohol consumption is a double hit, first as an immune suppressant, then as a major source of oxidative stress and reduction in protective glutathione levels. Two glasses of wine tonight followed by a COVID-19 sneeze in your face the next day could be the difference between an effective immune response (mild symptoms) versus an overwhelming life threatening infection!

Likewise, one night of inadequate sleep (which immediately suppresses immunity) followed by a COVID sneeze in your face the next day could have the same deleterious effect.

Below is a chart from the review article mentioned at the start of this post. Notice the top line states “ADDRESS SLEEP, STRESS, DIET, SUGAR, ALCOHOL

If you have been reading my posts on COVID-19, you have heard this before.

integrative medicine chart

Notice the second row in the chart with escalating doses of NAC as intensity of disease increases. When cytokine storm hits NAC dose recommendations peak and glutathione (available for IV administration) is recommended. IV glutathione surprisingly is not part of most hospital formularies and I have never seen it used in a hospital setting. Functional medicine physicians sometimes use it outside of the hospital setting. IV glutathione has become a sexy and lucrative office procedure in some functional medicine practices.

NAC has high bioavailability, meaning it is absorbed well in our gut. So oral supplementation can rapidly and effectively increase levels of glutathione in the body. IN FACT, treatment of acetaminophen overdose in the ER typically begins with oral NAC (often administered through a naso-gastric feeding tube, passed through the nose and into the stomach) Doses are often calculated by the regional poison control center (available by phone 24/7/365) and subsequent doses follow a standard protocol based on weight.

I would encourage you to read through this COVID-19 INTEGRATIVE MEDICINE review article.

It is thick with science but you might be surprised by how much you understand and learn.

In the chart above there is specific mention of Vitamin C supplementation in escalating doses as degree of illness increases. Vitamin C is an important anti-oxidant and in that sense is a glutathione sparing agent helping to mitigate glutathione depletion.

Other important factors mentioned in the article and the chart above include items mentioned here in previous posts: ZINC, ZINC IONOPHORES, phytochemicals (quercitin, EGCg, curcumin), Vitamin D, exercise, sleep, stress reduction, sunshine.

So I will close this post the way I have closed on many posts related to COVID-19.

Support your immune system.

  1. Avoid alcohol consumption (alcohol wreaks havoc with your immunity)
  2. Get plenty of sleep (without adequate sleep your immune system does not work well )
  3. Follow good sleep habits
  4. Exercise, especially out of doors in a green space, supports the immune system
  5. Get some sunshine and make sure you have adequate Vitamin D levels.
  6. Eat an anti-inflammatory diet rich in micronutrients.
  7. Practice stress reduction like meditation and yoga which improves the immune system
  8.  Eliminate sugar-added foods and beverages from your diet, sugar increases inflammation, contributes to metabolic dysfunction and impairs immunity.

In a future post I will describe my PERSONAL approach to dietary supplements in the context of COVID-19. I will also discuss the issue of an ADVANCED DIRECTIVE, in case you are hospitalized.

THIS WEBSITE PROVIDES INFORMATION FOR EDUCATIONAL PURPOSES ONLY. CONSULT YOUR HEALTH CARE PROVIDER FOR MEDICAL ADVICE.

Eat clean, drink filtered water, love, laugh, exercise outdoors in a greenspace, get some morning sunlight, block the blue light before bed, engage in meaningful work, find a sense of purpose, spend time with those you love, AND sleep well tonight.

Doctor Bob

Glutathione review links are below:

Glutathione!

Mitochondrial Glutathione, a key survival antioxidant

Glutathione: overview of its protective roles, measurement, and biosynthesis