December 6th, 2021
A new variant detected in South Africa is now a variant of concern. They are calling it omicron or B1.1.529 and it has 30+ mutations many of which are in the spike protein region making it a possible player in vaccine evasion, but this is not proven. In the next few weeks the vaccine companies will test the vaccine against this new variant and we will have more data. One vaccine company, Novavax is apparently making a vaccine against this variant already.
If this variant does indeed evade the current vaccines, we are looking at 3 plus months for a new vaccine to be made to combat this new player. Oh, these are truly interesting times that we are living through. I may never stop writing about this mess. Incredible.
What else do we know at this moment about this variant?
1) Omicron accounts for the majority of tested samples in South Africa as of November meaning that it appears to be outcompeting Delta for the previously uninfected or immunity waned post infection or vaccine. This is likely a new mutation induced fitness advantage making it unlikely to be more deadly as it is more infectious, but that is a guess.
2) We have zero solid evidence yet that it is more or less deadly. Early reports out of South Africa are that it is not more dangerous. It is primarily infecting the under 45 year old age group because they are the least vaccinated group and most interactive. This would be in keeping with predictions that mutations will offer more infectiousness or severity but not both. TOI Article. However, the morbidity and mortality reality for the US will only be understood here as we have a much less healthy population in general than South Africa and almost everywhere else on planet Earth.
3) Omicron is now in the United States and will declare itself in the coming weeks as a more fit version in our population or a pretender, but it looks to be significantly more fit than delta
4) Omicron shares mutations with the variant delta, but it has a dozen novel mutations on its spike protein. Omicron has 32 mutations in this region overall. This is the largest number that I have seen to date. There is legitimate concern that it will reduce the ability of our current infection or vaccine induced antibodies to neutralize it, making our mRNA vaccines less effective. Apparently, the mutations are all in the locations of spike antibody binding sites. This really makes vaccine and prior infection evasion possible and maybe even likely. (Mishra S. 2021) This is a big problem, but if and only if we see more deaths and hospitalizations from it. I fear that the unvaccinated and previously uninfected are in trouble. Everyone else is a massive guess right now.
5) "On the bright side, antibodies taken from people who were first naturally infected and then vaccinated were still able to neutralize a synthetic Omicron-type virus in the laboratory. That suggests a booster dose of an mRNA vaccine may still provide robust protection against Omicron." (Mishra S. 2021) This tells me that if we have circulating antibodies from an mRNA vaccine, we will have a jump start on the new variant and this will significantly limit viral load and thus disease severity. Again, this is a guess as this is a lab based analysis and not in vivo. See the **** area below for actual mutation details.
Herd immunity is highly unlikely now and we are going to have to get used to SARS2 from here on out. Delta and now likely Omicron are both likely to have a reproductive rate north of 6 which makes the need for global immunization to be in the 90 to 95% range for a chance at some reasonable societal immunity. Many experts are predicting yearly viral spikes of SARS2 in the lines of influenza or possibly greater. Hopefully, as statistics seem to show, we will see less and less death and hospitalization as more people are vaccinated or have survived a previous infection. Thus, it is likely that we are heading into the nuisance phase of the pandemic/endemic. Lots of illness with less and less morbidity year upon year. Hopefully, as the hospitalization and death data continues to be uncoupled from circulating infections, we will see the CDC and state officials work back to a more normalized society. Omicron could really mess up any of these plans though.
Another big issue remains the lack of vaccination in developing and larger population countries around the world. These are the hotbeds of variant development including new variants in Brazil, India, South Africa and others so far in the pandemic. We need to prioritize vaccinating first timers over boosters for healthy fully vaccinated adults.
Quick Hits -
1) SARS-CoV-2 infection induces neutralizing antibodies in all lean but only in few obese COVID-19 patients. SARS-CoV-2 infection also induces anti-MDA and anti-AD autoimmune antibodies more in lean than in obese patients as compared to uninfected controls. Serum levels of these autoimmune antibodies, however, are always higher in obese versus lean COVID-19 patients. Moreover, because the autoimmune antibodies found in serum samples of COVID-19 patients have been correlated with serum levels of C-reactive protein (CRP), a general marker of inflammation, we also evaluated the association of anti-MDA and anti-AD antibodies with serum CRP and found a positive association between CRP and autoimmune antibodies.
Conclusions: Our results highlight the importance of evaluating the quality of the antibody response in COVID-19 patients with obesity, particularly the presence of autoimmune antibodies, and identify biomarkers of self-tolerance breakdown. This is crucial to protect this vulnerable population at higher risk of responding poorly to infection with SARS-CoV-2 than lean controls. (Frasca et. al. 2021)
Obesity remains the greatest risk factor for all cause cancer, diabetes, autoimmunity and coronary/cardiac diseases. The greatest risk factor for obesity is the combination of high fat/high refined sugar diets, high fructose corn syrup, sedentary behavior, chemical exposure and chronic unremitting stress. Tackling each one will go a long way toward healing the risk of most disease especially COVID related problems.
2) Obesity research: The authors state: "We identify two cellular targets of SARS-CoV-2 infection in adipose tissue: mature adipocytes and adipose tissue macrophages. Adipose tissue macrophage infection is largely restricted to a highly inflammatory subpopulation of macrophages, present at baseline, that is further activated in response to SARS-CoV-2 infection. Preadipocytes, while not infected, adopt a proinflammatory phenotype. We further demonstrate that SARS-CoV-2 RNA is detectable in adipocytes in COVID-19 autopsy cases and is associated with an inflammatory infiltrate. " (Martinez-Colon et. al. 2021)
What this research tells us is that pre infection, obese individuals have fat cells that are polarized toward an immune inflammatory state that are further polarized post viral exposure. These same fat cells can be infected by SARS2 and further inflame the local tissue through tissue specific macrophages that release cell immune signaling cytokines. The phenotype of the cytokines is consistent with severe COVID disease.
3) "Superspreading events have distinguished the COVID-19 pandemic from the early outbreak of the disease. Our studies of exhaled aerosol suggest that a critical factor in these and other transmission events is the propensity of certain individuals to exhale large numbers of small respiratory droplets. Our findings indicate that the capacity of airway lining mucus to resist breakup on breathing varies significantly between individuals, with a trend to increasing with the advance of COVID-19 infection and body mass index multiplied by age (i.e., BMI-years). Understanding the source and variance of respiratory droplet generation, and controlling it via the stabilization of airway lining mucus surfaces, may lead to effective approaches to reducing COVID-19 infection and transmission." (Edwards et. al. 2021)
Roughly 20% of infected individuals were super spreaders whereas 80% were minimal spreaders which is inline with previous studies. The part that is of most interest is the age and obesity correlation. Advancing age and obesity carry a common theme of weakened immune activity. This allows for higher viral loads and increased viral shedding.
4) Autoimmune reactions are underlying acute psychiatric changes in adolescents post COVID infection. When a child has abrupt onset of hallucinations, anxiety, OCD like PANS or PANDAS disorders, we are now
learning that the etiology is autoimmune antibodies attacking brain cellular tissue inducing the symptoms that we are seeing. Even schizophrenic symptoms are to be related to autoimmune attacks in COVID patients even with mild respiratory disease. The antibodies target neural tissue and certain targets like TCF4 which can appear like schizophrenia.
5) If you are interested in an article on the current state of COVID treatments for severe disease, then this piece in the Annals of Internal Medicine is a good starting place, (Boggiano et. al. 2021)
6) We will get into this in a deeper context down the road when I interview Dr. Rick Johnson in January, but let's look at this briefly now. His work on fructose metabolism driving uric acid elevations and subsequent damage to the kidneys that we see of as high blood pressure is intriguing for these reasons:
a) If high fructose corn syrup and the beverages that are made from it and sugar are consumed in high volumes, the metabolite uric acid will rise which triggers the innate immune system locally to make inflammasomes and reactive oxygen radicals like hydrogen peroxide which cause local inflammation and damage to mitochondria and cells in general. These cells then can undergo apoptosis or programmed cell death which can inadvertently present self tissue to the adaptive immune system driving auto immune antibody development. This is now being shown to be a major mechanism in the development of high blood pressure as kidney cells are being targeted by autoimmune antibodies. (Chan et. al. 2014)(Caliceti et. al. 2017)(Vora et. al. 2021)
b) If a human consumes lots of liquid sugar as soda or juice coupled to added sugar in process foods, then it is highly likely that multiple pathways are disrupted including the intestinal microbiome, glucose and fat metabolism, immune solvency and activity. The innate immune activation from the uric acid, dysbiosis in the gut and fat tissue will drive a low level endotoxemia that will worsen the initial SARS2 viral surveillance and killing response followed by an overloaded immune inflammatory response that will tear up a lot of our de novo tissue. This disrupted tissue will lead to self antigen presentation and autoantibody formation. Thus, we have precursor risk with our dietary behavior. Once again, mechanisms of risk are presented here to give you the reader a pathway to the why we must change our behavior now as it relates to fructose, high fructose corn syrup and other added refined sugars.
c) Dr. Johnson believes that we should consume zero beverages with refined sugar or fructose. We should limit our consumption of fruit on a daily basis to a cup of berries or like fruit. We should try to rid ourselves of processed foods as they contain lots of hidden sugars.
d) I believe that these metabolic pathways are the reasons behind the increased risk of death from COVID for Americans that have co morbid diseases of obesity and metabolic syndrome.
7) In a French study looking at the risk of SARS2 transmission at indoor concerts with effective masking, 3 day pre event negative PCR and optimized ventilation in 18 to 45 years old persons with no comorbid disease, they found no increased incidence of infection between thousands of event goers and matched controls. (Delaugerre et. al. 2021) The value of this study is that we can use these and other studies as metrics to assess risk in large venues. As with airplanes, I am in the camp that ventilation and masking makes a big difference in close quarter environments. It truly is a swiss cheese model whereby multiple preventative modalities stack upon each other for risk prevention.
8) In the NEJM, a group studied reinfections with COVID in Qatar. They found that reinfections reduced hospitalization or death 90% versus primary infections. Four reinfections were severe enough to lead to acute care hospitalization but not in an ICU, and none ended in death. The group noted that reinfections were rare and mild. (Aba-Raddad et. al. 2021) These facts again are not surprising as the SARS2 primed immune system responds more rapidly to new viral exposure reducing viral load and risk.
9) A nice review of the DIVINE study in Reach MD by Dr. Todd Rice looks at the use of hydrolyzed formulas with low carbohydrate loads in critically ill patients. The end result as would be expected is reduced insulin use and better metabolic metrics which are associated with better outcomes. This is worth keeping an eye on if a family member is admitted for COVID critical care concerns and has issues with blood glucose control.
Happy Holidays,
Dr. M
Mishra National Geographic
Frasca Inter J Obesity
Martinez Colon MedRxIV
PNAS Edwards
Reach MD Autoimmunity
Boggiano Annals of Internal Medicine
Vora Nature
Chan Biomed Res Int
Komada Nature Reviews Nephrology
Ghaemi Rheum Rep
Caliceti Nutrients
Delaugerre Lancet ID
Aba-Raddad NEJM
Rice ReachMD
CDC MMWR
CDC Variants Page
****The 32 mutations that occur in Omicron’s spike gene can be organized into three groups, depending on how they alter the function of the spike protein, says Olivier Schwartz, a virologist and immunologist at the Pasteur Institute in France.
Some mutations enhance the spike protein’s ability to bind to the human ACE2 receptor; some help the surface of the virus fuse with the cell and allow the virus to enter; others alter the appearance of the spike protein, making it harder to recognize and allowing the virus to evade antibodies.
Of the many mutations on Omicron’s spike, the loss of amino acids at positions 69 and 70 makes the virus twice as infectious as the original virus. But in a stroke of luck, these two mutations are not present in Delta, making Omicron easy to distinguish in a widely used PCR assay.
The University of Cambridge’s Gupta has previously shown that these deleted amino acids, along with a third mutation at position 796 on the spike protein, are associated with Alpha’s ability to evade the body’s immune response. This suggests these same three mutations could help Omicron escape existing immunity either from vaccines or previous infections—and some preliminary evidence suggests that is happening.
“To date there have been a number of breakthrough infections, but they have been mild,” says Barry Schoub, a virologist and adviser on COVID-19 vaccines to South Africa's government. However, experts say it is too early to know whether Omicron causes more severe disease as there is a lag between infection and hospitalization.
Another cluster of mutations in Omicron at positions 655, 679 and 681 of the spike protein are thought to help the virus infect human cells more easily; they also exist in the Mu variant and are known to enhance its transmissibility.
Additionally, in a study not yet peer reviewed, researchers suggest that a mutation that Omicron shares with Alpha and Mu might help it replicate faster and resist immunity. And a mutation at the 501 position also found in Alpha, Beta, and Gamma makes the spike protein attach more tightly to the ACE2 receptor, making the virus more efficient at infecting cells.
Here is a cool youtube video on how the mRNA vaccine works in video form. Link
Redisplayed for those who missed it's significance
1) Diet and death - finally someone writes a quality article after 21 months of time gone by. In a well written article, Helena Evich tackles a topic at the national level that I have been waiting for for a long time. She writes: "In Washington, there has been no such wake-up call about the link between diet-related diseases and the pandemic. There is no national strategy. There is no systemswide approach, even as researchers increasingly recognize that obesity is a disease that is driven not by lack of willpower, but a modern society and food system that’s almost perfectly designed to encourage the overeating of empty calories, along with more stress, less sleep and less daily exercise,setting millions on a path to poor health outcomes that is extremely difficult to break from." "Glickman noted that the country’s leading voices on coronavirus, including Anthony Fauci, don’t focus on underlying conditions and what could be done about them long term. Instead, the focus is solely on vaccines, which have been proven to be safe and effective.
“They hardly ever talk about prevention,” Glickman said. “It’s missing. It’s a gigantic gap in the discussion about how health care relates to Covid and how it relates to the prevention of disease.”"
This article is a start, but we need more public messaging about the risks of food and disease risk.
In our race to control an uncontrollable pandemic, we allowed our heads of medicine, including Dr. Fauci, to flip flop around on the science, get themselves tied to untruths and scandals which in effect torpedoed an amazing vaccine effort that has saved countless lives. Trust evaporated rapidly among many laypeople and medical providers alike. There were a lot of intelligent people asking serious questions that needed to be met with science and understanding but instead were met only with censorship and more distrust. I have so much sadness for those that got stuck in the misinformation gap and paid the price with their lives. The science was there, but politics ruined the clear science and the truth.
Most importantly - the government needs to stop subsidizing the staple crops of corn, soy and wheat which drive the engine of cheap mass produced poor quality food and instead pay farmers to produce high quality vegetables fruits and meats for mass consumption. Let's make soda 6$ per can and an apple 30 cents. Wouldn't that be a step towards health!
I hear many say that we don't want a nanny state telling us what too eat. I agree. We already have a nanny state funding all of the garbage food that is driving us in the wrong direction. Two options exist for me. No subsidies at all or preferably subsidize high quality food for all children aged 0 to 21.
My 2 cents!
2) What are the antecedent risk factors of COVID induced disease in young children? "Approximately 30% of hospitalized children had severe COVID-19 and 0.5% died during hospitalization. Among hospitalized children aged <2 years, chronic lung disease (aRR=2.2, CI: 1.1–4.3), neurologic disorders (aRR=2.0, CI: 1.5‒2.6), cardiovascular disease (aRR=1.7, CI: 1.2‒2.3), prematurity (aRR=1.6, CI: 1.1‒2.2) and airway abnormality (aRR=1.6,CI: 1.1‒2.2) were associated with severe COVID-19. Among hospitalized children aged 2‒17 years, feeding tube dependence (aRR=2.0, CI: 1.5‒2.5), diabetes mellitus (aRR=1.9, CI: 1.6‒2.3) and obesity (aRR=1.2, CI: 1.0‒1.4) were associated with severe COVID-19. Severe COVID-19 occurred among 12.0 per 100,000 children aged <18 years, and was highest among infants, Hispanic children, and non-Hispanic Black children."(Woodruff et. al. 2021)
This group of children should absolutely line up for a covid vaccine based on the current data stream.
