COVID-19 Vaccine Safety Part I

January 17, 2021 8 Comments

A scanning electron microscope image of SARS-CoV-2

 

I would like to preface this blog with the assertion that I am not against the COVID-19 vaccine and all it symbolizes. A safe and effective vaccine against COVID-19 would be a remarkable achievement.  

There is currently no evidence that any of the coronavirus vaccines worsen coronavirus infection rather than confer immunity to it, but this phenomena, called Antibody Determined Enhancement  (ADE), WAS supposed to be something scientists closely monitor. In the meanwhile, medicine brings no attention to this concern and is completely ignoring that ADE is the reason we have never had a successful vaccine against coronaviruses after the 2002 SARS-CoV-1 epidemic.

We knew that the earlier severe coronavirus (SARS-CoV) carried the potential for reemergence since the Severe Acute Respiratory Syndrome (SARS-1) outbreak in 2002. Hence, researchers have been trying to develop a coronavirus vaccine since that time. Yet, these efforts have historically been thwarted by ADE.

SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), is closely related to SARS-CoV (with ~80% sequence identity), which caused the SARS outbreak in 2002. Its next closest human coronavirus relative is Middle East respiratory syndrome-related coronavirus (MERS-CoV), which caused Middle East respiratory syndrome in 2012. SARS-CoV-2 is also genetically related to other endemic human coronaviruses that cause milder infections.

A major goal of the COVID-19 vaccine development is to generate antibodies that prevent the entry of SARS-CoV-2 into cells.

Antibody-dependent enhancement, ADE.

Ever heard of it? I thought not. ADE resembles Cytokine Storm in its worst presentation and Cytokine Storm is what kills people with our current SARS-CoV-2 infection.

Cytokine storm

Cytokine Storm is not new to humans and the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) pandemic has reminded us of the critical role of an effective host immune response and the devastating effect of immune dysregulation. This year marks 10 years since the first description of a cytokine storm.

The term Cytokine Storm denotes a hyperactive immune response characterized by the release of mediators that our immune system utilizes to destroy and clear infectious agents. Cytokine storm implies that the levels of released cytokines have become injurious to our cells.

In a nutshell, whenever a healthy body is fighting an infection, the natural immune system response that occurs involves releasing cytokines that essentially signal the immune system to start doing its job. Cytokines are meant to be helpful to us in moderation, but when a certain pathway is engaged too much, the immune system starts causing damage to the patient through cytokine mediated inflammation in the body. It is at this juncture that if cytokines, which normally play an important role in our healthy immune responses, are released in large amounts all at once, cytokine storm can ensue. Cytokine storm seen in COVID is responsible for Acute Respiratory Distress Syndrome (ARDS) and life threatening multiple organ failure which can lead to death from systemic inflammation and organ shut down.

Antibody-dependent enhancement, ADE

In some instances, the presence of specific antibodies to a virus are actually beneficial to the virus. Known as Antibody-Dependent Enhancement (ADE) of virus infection, the ADE of virus infection is a phenomenon in which virus-specific antibodies enhance the entry of virus, and in some cases the replication of virus, i.e. upregulate viral infection and potential infectivity. Besides the common receptor/coreceptor‐dependent mechanism of cellular attachment, the fact that viruses can rely on antiviral antibodies for their efficient entry into target cells has been well known now for over 20 years, makes Antibody-Dependent Enhancement (ADE) of virus infection by vaccines a very important potential to avoid and carefully watch for, PRIOR to global vaccination. To make matters worse, ADE associated with SARS-CoV infection has been historically shown to be primarily mediated by the Anti-spike antibodies, the very ones we produce with the vaccine in our body.

Antibody Dependent Enhancement (ADE) of a disease is always a concern for the development of vaccines because the mechanisms that underlie antibody protection against any virus has a theoretical potential to amplify the infection or trigger harmful immunopathology, resembling cytokine storm.

ADE was first seen in natural viral infections with the Dengue virus and some of its relatives. ADE has been observed in SARS, MERS and other human respiratory virus infections including RSV and measles.

Essentially, ADE is associated with decreased levels of the anti-inflammatory cytokines in our body and increased levels of the pro-inflammatory chemokines. It is seen in individuals with secondary infection, or if infected after vaccination for the virus.

The concern is that when people are:

  1.  re-infected with particular pathogens (one of my concerns is how does this differ from vaccinating previously SARS-CoV-2 infected patients; a practice encouraged by the medical community with zero safety data)
  2.  inoculated with vaccines that work by priming the patient for infection when snippets of virus to mimic a first infection are injected into the body

How do we know without extensive investigation whether those antibodies created during the first-time infection (or with vaccine) do not end up enhancing the disease rather than protecting against subsequent infections?

Called Antibody-Dependent Enhancement;  ADE, has been demonstrated in animals during the coronavirus vaccine research since 2002. Therefore this research never progressed to human trials, not at least until the recent SARS-CoV-2 vaccine, where currently the millions of humans receiving the vaccine are the primary test animal.  Remember, the reason for LENGTHY vaccine safety investigation is just that. We are not limited to immediate collections of data for reactions to the vaccine. A mild fever, body aches and fatigue are really all that are currently reported 2 months into the Pfizer and Moderna studies. What about long-term adverse effects? No data.
Always ask the question....how will I know if a future medical issue  I may develop, is not related to a vaccine whose safety was untested and whose regulation was lost with EUA. This is the biggest issue on the chalk board right now...followed by way too many question marks! Putting aside that fact that the mRNA vaccine is a new vaccine never to be used to inoculate a human (for reasons that are in a future blog), we must be smart about CONCERNING and unrevealed reasons that the coronavirus has not proven eligible for a safe and effective vaccine.

Remember there is significant scientific knowledge of the potential risk for any COVID-19 vaccine exacerbating COVID-19 severity via antibody-dependent enhancement (ADE) in the scientific community, which is disregarded when the FDA approved the EUA of the COVID-19 vaccines.

Going forwards, it has been considered CRUCIAL by the scientific community  to evaluate animal and clinical datasets for signs of ADE, and to balance ADE-related safety risks against intervention efficacy if clinical ADE is observed. Ongoing animal and human clinical studies were to provide important insights into the mechanisms of ADE in COVID-19. Such evidence is sorely needed to ensure product safety in the large-scale medical interventions required to reduce the global burden of COVID-19. 

YOU ASK WHERE ARE THE STUDIES and WHY DOESN'T MEDICINE TALK ABOUT COVID-19 SAFETY on this level???

GOOD QUESTION. Remember EUA?

 What is EUA?

In certain emergencies, the FDA can issue an Emergency Use Authorization (EUA) to provide access to medical products that may potentially be used when there are no adequate, approved, and available options.

The EUA process is different than an FDA approval or clearance. Under an EUA, in an emergency, the FDA makes a product available to the public based on the best available evidence, without waiting for all the evidence that would be needed for FDA approval or clearance.

  After two decades of failed vaccine trials in animal, why EUA a coronavirus vaccine for humans without a well-established safety profile??

Answer: the Vaccination Dilemma

The Vaccination Dilemma is defined as competition between a clinical trial for vaccine efficacy and safety as well as long-term value and it's emergency use. Remember, once a vaccine is granted emergency approval, there is pressure on developers to offer the immunization to trial participants who received the placebo. But if too many people cross over to the vaccine group, WE LOSE OUR CONTROL PLACEBO group. This means the companies lose the data to study and to establish long-term outcomes of efficacy and safety.

Why is this important? Other than the obvious, "WE LOSE OUR CONTROL PLACEBO group. This means the companies lose the data to study and to establish long-term outcomes of efficacy and safety", let's also answer this question with a return to the Pfizer and Moderna studies that led to EUA. Of the 70,000 people that entered the 2 company studies and were divided into vaccine and non-vaccine ( placebo) groups, the 95+% efficacy of the vaccines was extracted from 0.5% of this testing population, 4-5 weeks into their respective Phase 3 (human) studies. The statistical ethical issue I raise in this measurement comes from the fact that only 0.5% of the 70,000 patients between the two groups were used to create the touted 95% efficacy. PLUS, this statistic came only 8 days after the 2nd vaccine was provided in both groups. Yes, of the 70,000 people between the two studies, less than 350 people between the two study groups was used to generate the 95% efficacy statistic which led to EUA approval, 8 days after the 2nd vaccine inoculation. 

My hopes:

With the knowledge that antibody-dependent enhancement, ADE, occurs with coronaviruses, there is a real risk for ADE with the SARS-CoV-2 vaccines. But, the hope is that we will reduce the risks of ADE of SARS-CoV-2 with the COVID-19 vaccines if we deliver high doses of potent neutralizing antibodies, rather than lower concentrations of non-neutralizing antibodies that would be more likely to cause ADE. So the hope is that the mRNA vaccines we are using will avoid the possibility of generating non-neutralizing antibodies that are not strong enough and can cause ADE.

“If you’re just giving the immune system the only choice of making an antibody”, like we do with the mRNA, then you drastically limit the possibility of inducing ADE,” states James Crowe, an immunologist at Vanderbilt University Medical Center. “This is very hard to study in humans”, he goes onto affirm.

 My strongest recommendation for all my readers is to please take into consideration the lack of real scientific support either the Moderna or Pfizer drug companies have right now to substantiate their safety. 

COVID research is seriously looking into and demonstrating efficacy of anti-inflammatory drugs to prevent COVID deaths. Does this come as such a surprise to you, the reader, after what you just read about Cytokine storm and ADE in this blog? 

Natural Immune Support and Inflammation Prevention

Although recommended to many patients for their SARS-CoV-2 prevention and treatment program, I have not raised my all time favorite choice for thwarting systemic inflammation to the table in a blog. So, please consider adding ENFLA-MEND to your repertoire for cellular health and inflammation prevention. 

 Enfla-Mend Px balances NF-kB (nuclear factor- kappa B), mediating inflammatory cytokine release.

This formula supports the total body to include brain health and works as a natural anti-oxidant, neutralizing (reduces) inflammation:

  • Highest curcumin essential oil content and turmerones per cap in the Industry
  • Lipophilic curcuminoids have been shown to be able to cross the blood-brain barrier.
  • Turmerones support healthy neural stem cell proliferation and neuroprotection.
  • Curcuminoids support the body’s natural action of clearing beta-amyloid plaque within normal range
  • Curcuminoids support normal acetylcholine levels

 Please take 2 daily.

 Another blog will review the data regarding the significant negative correlation (i.e. inverse relation = lower the level of D associated with increased COVID Infection cases) observed between mean vitamin D levels and COVID-19 cases. For now, remember Osteo-Px because Vitamin D is part of an ancient complex molecular effort to protect our immune system in every imaginable way. But Vitamin D's ability to do its work is created by the molecular dance on receptors of the human cell when A, D, and K work together. These lipid-based molecules are all powerful antioxidant nutrients which are intricately bound through shared receptors. They balance and enhance each other, and as a group, profoundly influence genes, immunity, inflammation, and the healthy balance of life in our body. Please take 1 daily. 
Please remember, I welcome questions and comments and that the best forum for this is on the blog. 
ALSO remember, STAYWELL - this is the 15% discount code provided for all supplements purchased through the website to those who support the blog and our network of communication with one another!
Stay Tuned and STAYWELL!
Ariane Cometa MD
your holistic doc

 

 

 




8 Responses

Jenny Dyer
Jenny Dyer

February 03, 2021

Thank you, Dr. Cometa! I’m going to share this with my family. This helps me understand how the numbers people have been touting were derived and what they mean. Best wishes.

Ariane Cometa MD
Ariane Cometa MD

January 30, 2021

Hi Jane,
Thanks for the question:
The resource for the small number of subjects and short testing period for determining the efficacy is actually Pfizer and it is published in the NEJM article, published Dec 31, 2020, “Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine”. “A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19” is based upon “A total of 43,548 participants underwent randomization, of whom 43,448 received injections: 21,720 with BNT162b2 and 21,728 with placebo. There were 8 cases of Covid-19 with onset at least 7 days after the second dose among participants assigned to receive BNT162b2 and 162 cases among those assigned to placebo”. So, doing the math, 162 (people in the placebo group, 7 days after the second vaccination dose,) was divided by the total amount infected with COVID 7 days after the second vaccination dose- 169 ( includes 7 infected after 2nd vaccination dose in those who received vaccine ) is 162/169= 95%. SO this statistic came from a population of 169 people, 1 week after second vaccination dose. Not good science. AKC

Jenny Dyer
Jenny Dyer

January 30, 2021

Hi, Dr. Cometa — Thanks very much for this. I’m especially concerned about the small number of subjects and short testing period for determining the efficacy. Could you please let me know the source for that info? Thanks!

Ariane Cometa
Ariane Cometa

January 17, 2021

Hi there Helen and Mike,
Great! That is my hope…that folks spread the blog to help people feel informed with the science regarding SARS-CoV-2 and how to approach both prevention and treatment. More to come!
All my love,
Dr. Cometa

Helen Royal
Helen Royal

January 17, 2021

Thank you so much, Ariane. I’ll be sending your information out to family and friends starting tonight!

Ariane Cometa
Ariane Cometa

January 17, 2021

Thank you so much Jennifer and Mary Allison for your Comments. It is so appreciated. Most important to me at this time is that folks know the science out there, rather than the medical rhetoric regarding the approach towards SARS-CoV-2. I will do my best to keep everyone informed.

Ariane Cometa MD
your holistic doc

Mary Allison
Mary Allison

January 17, 2021

Wonderful explanations and I have passed them on. Thank you so much. Too many of my elderly friends have done no research and have already started the vaccines…..

Jen Gately
Jen Gately

January 17, 2021

Many thanks for this detailed analysis. Really important to get the truth from an educated source like yourself.

Leave a comment

Comments will be approved before showing up.