February 8th, 2021

It is amazing to think of where we are compared to a year ago. So many predictions. Most of them wrong. None of this is surprising. First, the good news. We are continuing the trend in the right direction. The variants circulating now have not significantly changed the infection trend in the US, yet.

The bad news. The real concern now is can we get the virus under control before mutations start to stack up and thwart the vaccine effort. As an RNA virus, SARS2 makes a lot of replicative mistakes during it's self copying events. Many are corrected but some are not. If the mutation confers a benefit to the virus,

it will likely stay and gain traction as we are now seeing with the three new variants. The vaccine data that is emerging from the three major companies, Pfizer, Moderna and Novavax is showing roughly 90% or more efficacy against the original strain but significantly lower effect against the South Africa variant.

This is mixed but mostly negative news. On one hand 50% is better than 0%, but far less than 90% needed for a quality herd immunity and thus control. I am becoming more aligned with vaccination for all as this new problem could be a train wreck if a mortality increasing mutation occurs.

Let me explain for those that are afraid of the vaccine. Yes, it is new technology. Yes, it is possible that down the road we will find a rare side effect for a very small subset of vaccinated humans. Yes, it is possible that many things can go wrong. However, we are in a lose lose situation as I have said many times. The lose on the mutating virus side is orders of magnitude more risky than vaccination for most or all at this point. Whether this virus was natural or a biohazard accident is irrelevant at this point. It is here in all its glory.

Let us say that 60% of Americans and for that matter the global population get vaccinated. The other 40% continue to get infected, most will be asymptomatic, others will have diverse outcomes burdening the medical systems of the world for years to come. 5% of the vaccinated will have a poor vaccine response and will also get sick. Therefore, almost half of the world continues to get ill and pass along this virus. Not good for a planned return to normalcy.

I shudder to think of the ramifications of this virus circulating at these ebb and flow levels for another year or more. Does it mutate in a more deadly way? Does it start to target children? Does it really disable more people for good? Can people handle this level of mental and physical stress for that long? Are our children losing out because of another year of poor quality virtual education? There are so many ifs?

Here is a link to a Scientific American Article on the mutations in circulation. (Reardon S. 2021) Also see #11 below for an excellent report on the variants.

At current vaccination rates, it will take a year to get this country vaccinated. Now let's assume that we pull that off and no major variants ruin the immunity through vaccination by then. Now we still have to hope that the rest of the world is capable of effective vaccination so as to avoid a new "somewhere" variant that returns us to ground zero. The reason that polio still exists on the planet is because a few countries refuse to effectively vaccinate for it keeping it alive. The world of virology is simultaneously beautiful and deadly.

Now to the Quick hits

1) One thing is abundantly clear. Masking and social distancing works to slow the spread of the common cold and influenza in children and therefore society as a whole. We are in the month of February and the flu is nowhere to be seen in clinic. We are normally inundated with flu at this juncture in the calendar cycle.

Therefore, I do not need a study to tell me that the current efforts to control COVID are effective as tools against the flu and other viral respiratory illnesses for all of us.

At this point, I would double down on these measures moving forward.
a) Wash your hands for 20 seconds with common soap and do not touch your face until your hands are clean
b) Wear a high quality surgical or N95 type mask when out and about where people are, especially crowds
c) Eat super healthy, exercise daily, get 8 hours of sleep, take supplemental vitamin D , zinc and omega 3 fats, meditate and pray on your own inner peace and stress
d) Get vaccinated when your time comes up
e) Avoid chemicals and toxins that suppress immune function

2) Furthering the Autoimmunity discussion, let us look at Dr. Vojdani's most recent paper in Frontiers in Immunology. It is deep but worth your time. He goes through a series of points regarding the risk of autoimmunity from SARS2 and potentially the vaccines being used. It is one of the better articles written to date. As discussed 2 weeks ago, the SARS2 virus has been shown to have similar protein structures within it to our native tissue. According to Dr. Vojdani, "We applied both human monoclonal anti-SARS-Cov-2 antibodies (spike protein, nucleoprotein) and rabbit polyclonal anti-SARS-Cov-2 antibodies (envelope protein, membrane protein) to 55 different tissue antigens. 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."(Vojdani et. al. 2021) What he says here is that in a lab, his group was able to show that the SARS2 antibodies can and likely do attack our healthy tissue leading to autoimmune damage in the acute illness in susceptible patients. The key here is in susceptible individuals. Who these people are remains to be studied with regard to COVID. Yet, people at risk for autoimmune disease in general have strong family histories of autoimmunity and likely suffer symptoms of autoimmune disease themselves. (Khamsi R. 2021)

Therefore, let us say again, what is the immunological reality if you get the wild type infection versus the mRNA vaccine? If we state that we believe that SARS2 is causing immune mediated auto reactivity in select individuals when we get sick and we have mechanistically shown this to make sense as COVID is an inflammatory disease that can damage our cells making their proteins available for auto presentation based on our immunological status pre and during the infection, then we must define risk between groups. (Woodruff et. al. 2020)(Lerma et. al. 2020)(Vojdani et. al. 2020)(Kanduc et. al. 2020)

Risk from a wild type infection will robustly challenge our immune system by allowing it to see many protein pieces of the virus as it replicates and spreads throughout our tissues. The vaccine on the other hand is only presenting the one spike protein to the immune system after the messenger RNA teaches our cells to make the proteins and the immune system produces antibodies to it. This is only one viral protein type or epitope that the immune system can cross react with against our self tissue versus wild type infection which Dr. Vojdani has shown could be up to and beyond 28 protein fragments. It is at the minimum a 28 to 1 difference in auto reactive risk between wild type infection and vaccination. It is likely significantly worse than that.

Restated and reinforced another way, the true SARS2/COVID19 infection causes a ton of inflammatory tissue damage coupled with exposure to all of the SARS2 protein structures that the virus has including the many different spike proteins, envelope, membrane and the nucleocapsid. (SARS2 proteins) Our immune system can target any and all of these viral proteins producing SARS2 antibodies that can as shown above see our native barrier proteins, gastrointestinal, thyroid and neural tissues as foreign invaders and begin to attack us. This is exactly how autoimmunity occurs and is most likely occurring in COVID.

Risk: 1) Females are 7 times more likely to develop autoimmune disease in general than men. 2) SARS2 attacks males more aggressively based on our relative lack of interferons and antibodies against interferons. 3) Autoimmunity clearly follows a genetic predisposition coupled with an inflamed immune mileu. This inflamed milieu is defined by metabolic derangements that we call diabetes, obesity, cardiovascular disease and insulin resistance.

I repeat, at this point, we stand again at a fork in the road. No treatment is perfectly safe and that is certainly true of a new, novel technique no less, vaccine. Go left for wild type disease and autoimmune risk that is significant based on the research or go right and run the theoretical risk of autoimmunity to one singular protein if it occurs at all. I am pegging the risk as probably significantly greater than 25 to 1 based on my reading to date. I am a firm believer in choice. I know my choice. Now you are armed with more data and can get closer to making your own if you have not already. (Kostoff et. al. 2020)

3) Diabetic patients have markedly upregulated immune cytokine profiles. (Zheng et. al. 2021) As stated above, immune dys-regulation is the key second step in the autoimmune cascade. If diabetics have increased volumes of cell signaling cytokines and chemokines that are telling the immune system to ramp up and fight, there will potentially be increased self tissue destruction and antigen presentation leading to autoimmunity in susceptible persons. This at first blush seems odd as everyone knows that diabetic patients have less functional immune systems not ramped up ones.

Why would this be?

At the microscopic immune level, these individuals had elevations in the inflammatory signaling molecules like IL-6 an dTNFa as well as professional antigen presenting cells like helper CD4 T cells, but unfortunately they also had decreases in viral killing CD8 T cells. The immune makeup of a type 2 diabetic is dramatically broken in favor of viral survival and dysfunctional self defeating autoimmunity.

As we had seen in the past, controlling the diabetes with diet and medication will slow down or reverse these negative immune effects.

The continued thrust of every argument for healthy survival is to avoid the antecedent causes of inflammation, intestinal dysbiosis and subsequent immune dysregulation. The first principles theory is at play here. Go back to the headwaters to prevent disease. Exercise, eat healthy whole natural fresh foods, avoid chemicals and maintain calm.

Also, now they are using "the novel SODA score (based on sex, peripheral O2 saturation, presence of diabetes, and age) demonstrated good accuracy for adverse events prediction." (Lopez-Pais et. al. 2021) Older age, being male, having a low oxygen level and having poorly controlled diabetes are all poor outcome indicators.

There is a direct link between our lifestyle choices, microbiome composition, disease morbidity and finally COVID death risk. 95% of deaths are defined by this paradigm. (Yeoh et. al. 2020)

4) The new genetic variant of SARS2 may be slightly more deadly. Early estimates are raising the death risk by 35% from previous numbers. In other words, if 1.3 out of one hundred known infected individual cases, case fatality rate, died from the old strain, the new variant is closer to 1.8 per 100. Again, this is not infection fatality rate which is markedly lower based on asymptomatic case unknowns.

5) "Asymptomatic persons seem to account for approximately 40% to 45% of SARS-CoV-2 infections, and they can transmit the virus to others for an extended period, perhaps longer than 14 days. Asymptomatic infection may be associated with subclinical lung abnormalities, as detected by computed tomography. Because of the high risk for silent spread by asymptomatic persons, it is imperative that testing programs include those without symptoms. To supplement conventional diagnostic testing, which is constrained by capacity, cost, and its one-off nature, innovative tactics for public health surveillance, such as crowdsourcing digital wearable data and monitoring sewage sludge, might be helpful." (Oran et. al. 2020)

In the British Medical Journal, we see data noting that one in four previously infected individuals was asymptomatic while 40% of the symptomatic patients did not have fever, dry cough or loss of smell. (Mahase E. 2021) Between the two studies, we have a significant asymptomatic spread concern and also highly variable clinical presentation.

This is truly the problem with SARS2. We have little clue when an asymptomatic spreader is in our midst and with symptoms being all over the map, we have no clue who has what. Rapid and reliable testing is the only way forward based on this data.

6) Spread on surfaces? In a very thoughtful Nature article, the author discusses the relevant data regarding the ability of SARS2 to infect individuals from a touched surface. (Lewis D. 2021) The primary route of spread remains from an aerosol droplet and not from a surface. Proper hand washing is the best way to prevent the rare but possible spread via a touched surface.

7) Individuals between 20 and 49 years of age have been the major source of viral transmission. The authors state, "We estimate that as of October 2020, individuals aged 20-49 are the only age groups sustaining resurgent SARS-CoV-2 transmission with reproduction numbers well above one, and that at least 65 of 100 COVID-19 infections originate from individuals aged 20-49 in the US." (Monod. et. al. 2021) Stringhini and colleagues found that the majority of spread was in the same age group. (Stringhini et. al. 2020)

This data mirrors the in school transmission data sets from 2020 showing that most transmission occurs in the adults outside of the school setting during the adult regular activities. In all of the studies to date, we see over and over again that children are not the source of spread.

It is not surprising that young adults are the spread source based on risk taking behaviors coupled with the volume of ACE2 receptors for viral attachment. Younger children are not physiologically getting infected frequently and the older population is averse to risk. The pandemic lockdown fatigue coupled with poor governmental messaging left the young adult population confused and tired of following mixed state based rules.

We need to use these data sets to encourage all young adults to wash their hands, wear a mask and get vaccinated lest the pandemic rage on into a mutation that is more deadly or capable of hurting the youngest among us.

Nothing is predictable but prevention is always worth a pound of cure. It would be a nightmare to see this virus mutate into a more formidable killer.

8) You may only need one vaccine if you have already been infected and recovered according to a new study by Krammer et. al. They noted that the antibody response after one vaccine dose in a previously infected person was greater than or at least equal to a naive person after two doses. (Krammer et. al. 2021) This information could be used to help prioritize vaccine delivery.

9) Mother's COVID positive status and their newborns? JAMAPediatrics notes: "In this cohort study, maternal IgG antibodies to SARS-CoV-2 were transferred across the placenta after asymptomatic as well as symptomatic infection during pregnancy. Cord blood antibody concentrations correlated with maternal antibody concentrations and with duration between onset of infection and delivery. Our findings demonstrate the potential for maternally derived SARS-CoV-2 specific antibodies to provide neonatal protection from coronavirus disease 2019." (Flannery et. al. 2021) This data set fits with what we are seeing in clinic. Newborns born to COVID positive mothers are remaining asymptomatic and COVID negative due to the transferred antibody protection. The acutely sick mother within days of delivery may not benefit the child in this way however, we have yet to see a COVID positive newborn.

10) Being a long term smoker increases your risk of hospitalization and death by roughly 2 X. (Lowe et. al. 2021) These are completely expected results as smoking is the independent risk factor for most healthcare related chronic and acute mortality concerns.

11) In an excellent report called the Rise of the Variants by Otello Stampacchia, we see a cogent analysis of the variant dilemma. I encourage everyone to read it. Here is the link.

12) If you missed it, there is a really nice predictive essay from McKinsey and Company that is worth your time.

13) Mask wearing is the least that we can do until things slow down and vaccinations are in full effect. They work folks. The absolute reduction in transmission in our clinic of SARS2 and also influenza community wide is a testament to the interventions role in control. In a study by Rader and colleagues, they found a significant benefit in infection reduction through mask wearing. (Rader et. al. 2021) While it is a pain to do, it is useful and should be universal at this time. (Howard et. al. 2021)

14) Loss of smell is not an attack on the olfactory "smell" neurons but instead on the ACE2 receptor carrying support cells. These cells are ciliated and were found during pathological analysis of COVID patients to be dysfunctional. These support cells have specialized salt ions and beating cilia that receive odors, register them and transmit them to the nerve in order to signal the brain of a smell. When studied, the cilia of infected olfactory regions were totally detached and non functional rendering the ability to smell lost. The nerve itself was normal. The same appears to be true with taste receptors of the tongue in individuals who lose taste function. The nerves are fine while the support structures are not. (Sutherland S. 2020)

Losing your sense of taste, smell or sensations around either can be distressing and also dangerous. Being unable to smell a gas leak or dangerous chemicals can harm you. You may not be able to smell spoiled food, milk or any toxic substance. Not being able to chemically sense a ghost pepper or other dangerous food could damage your GI tract. Losing pain receptors may make noting a hot beverage impossible.

As noted already, 95% of individuals that lose smell and taste will get it back within 6 months. For the remainder, it is hope and a prayer for resolution. As always, follow the anti-inflammatory guidelines to enhance resolution where possible.

15) If you are unlucky enough to have SARS2 find its way into your brain, the outcome would not be good according to translational models. (Kumari et. al. 2021)

16) Pregnancy and the COVID vaccine. There is absolutely no data on the safety of COVID and the pregnancy state. The animal models are the only data in existence which is a poor indicator of human responses while pregnant. To get the vaccine while pregnant is a complete crapshoot.

While there are increased risks of COVID while pregnant according to the data, the other fork in the road is a complete unknown making it scary at the least.

There is absolutely no reasonable guidance to be given with regard to the COVID vaccine and pregnancy.

I will endeavor to explore the pregnancy conundrum more in the coming weeks.

CDC site on pregnancy

Dr. M

Reardon Scientific American
Vojdani Frontiers Immunology
Khamsi Nature
Kaneko Cell
Woodruff Nature Immunology
Woodruff MedRxIV
Lerma J Transl Autoimmunity
Vojdani Clinical Immunology
Kanduc Immunology Research
Kostoff Toxicology Reports
NYTimes Magazine Baker
AAP Numbers
Zheng J of Diabetes Research
Lopez-Pais Preventative Medicine Reports
Oran Annals of Internal Medicine
Mahase BMJ
Lewis Nature
Monod Science
Stringhini Lancet
Krammer MedRxIV
Yeoh Gut
Lewis Nature
Flannery JAMAPediatrics
Lowe JAMANetwork
Rader The Lancet
Stampacchia Report
Howard PNAS
Sutherland Scientific American
Kumari Viruses