October 25th, 2021

North Carolina is back to relative normalcy in most places.

If you have had 2 doses of an mRNA vaccine, you have a very very small risk of a significant hospitalization and therefore death from the Delta variant based on statistics overall.

Being Unvaccinated now is the greatest risk factor for a negative outcome. Advancing age and co morbid disease add layers of risk on top of the vaccination status

Latest numbers google/CDC

We are continuing to see that the lambda, gamma and mu variants are not an issue yet and likely will not be in the United States as delta is outcompeting them.

As it stands today, the United States has had 45.4 million known cases and almost 736,000 deaths. There has been a significant downtick in deaths over the previous 2 week cycles as case volume has plummeted.

If you did not read the newsletter about an Integrative approach to health in the COVID era, read this link and this link.

As with the first newsletter on this topic, keep solace with the fact that there is a 99+% chance of survival for all of us regardless of vaccination. However,
mathematically, you now have a 99.9998% chance of survival once vaccinated and the vaccine safety for the mRNA vaccines continues to look good.

Why take on that extra risk?

 

 According to the American Medical Association, 96% of medical doctors have received a Covid vaccine nationally. That says a lot about the safety of this vaccine. Physicians are loathe to receive interventions that have not been well studied for safety as we see the train wrecks of intervention failures in our patients. This information should really help those that have been sent down the wrong path by the poor political messaging around vaccination nationally. If you are over 18 years of age, please consider vaccinating if you have not already done so. This decision may save your life.

 

Comorbidity risk reassessed 20 months in to the pandemic. From Dr. Antos and colleagues: "A total of 39,451 COVID-19 deaths were identified from four States that had comorbidity data, including Alabama, Louisiana, Mississippi, and New York. 92.8% of the COVID-19 deaths were associated with a pre-existing comorbidity. The risk of mortality associated with at least one comorbidity combined was 1113 times higher than that with no comorbidity. The comparative analysis identified nine comorbidities with odds ratios of up to 35 times higher than no comorbidities. Of them, the top four comorbidities were: hypertension, diabetes, cardiovascular disease, and chronic kidney disease. Interestingly, lung disease added only a modest increase in risk. (Antos et. al. 2021)

The common theme remains that what makes you inflamed and prone to disease puts you at risk for death or hospitalization from SARS2. The main driver of these disorders remains poor lifestyle decisions over time. Poor quality nutrition is #1 closely followed by unremitting mental stress. Sloth and chemical exposure in toxic loads or of lesser volume over a chronic time period are also driving immunometabolic inflammatory dysfunction.

As SARS2 is now endemic, it is hard to predict the future. However, it is highly likely that those among us that practice poor quality lifestyle actions on a prolonged basis will suffer sooner or later with COVID as we age. Age seems to be a defining factor in risk for many reasons:

1) As we age, our immune function is weakened
2) Vaccine responses weaken
3) We are inflamed for longer increasing the risk of co morbid disease
4) Bad luck happens over time with other illnesses or accidents that make us vulnerable to infection

Thus, the only real take home to all of this data at this point is as follows:
1) Vaccinate with at least two doses if never infected or one dose if previously infected
2) Consider a booster shot based on co morbid risk and age
3) Work very hard to reduce all antecedent triggers for inflammation as discussed ad nauseam in this newsletter
4) Make sure to take all of your medicines on a regular basis to keep inflammation to a minimum

Quick Hits -

1) The vaccines work against hospitalization and death despite Delta's ferocity. "Among U.S. adults without immunocompromising conditions, vaccine effectiveness against COVID-19 hospitalization during March 11–August 15, 2021, was higher for the Moderna vaccine (93%) than the Pfizer-BioNTech vaccine (88%) and the Janssen vaccine (71%)." (CDC)

The real point here is that the variants will be controlled by the vaccines unless there is a full key shift in the spike protein which is exceedingly unlikely to happen. Thus, for every American, there is a 7 to 12% chance of a negative breakthrough event that could require hospitalization if you had Moderna or Pfizer respectively. The preponderance of these breakthroughs that end up in the hospital will occur in the same demographic groups that were at major risk pre vaccine:
1) People over 65 years of age
2) People with obesity, coronary vascular disease, diabetes, high blood pressure and kidney disease
3) People that are immune suppressed significantly

Everyone else, in general, should do very well post vaccination.

The natural ability of the immune system to handle the mild antigenic changes in SARS2 variants is very well on display right now. Our immune reactions are beautiful to witness.

Redo for significance in the future: Let us take a deeper dive into the technical world of B cell memory and therefore lasting protection post vaccine or natural illness. Once you have seen the virus' RNA protein fragment as either a spike fragment from the mRNA vaccine or chopped up portions of the natural virus, your immune system will present this sequence to the B cell in an elegant way called antigen presentation that will develop a subspecies of B cell called the Memory B cell which has the distinctive ability to be quiescent and long lived in our bone marrow after the SARS2 virus is dead and gone. The entire purpose of the long lived memory B cell is to have the ability to re recognize the SARS2 virus when it returns. The rapid RNA sequence recognition based on this memory allows for the immediate development of neutralizing antibodies that squash the SARS2 virus rapidly next time around.

What about the variants? We know that the SARS2 virus mutates at a modest pace. If the SARS2 RNA has changed its structure during a mutation, let's say from alpha to delta, does the memory B cell still have immune ability or do we lose immune recognition? Here comes the beauty of the human immune system.

Do you remember the stories of people getting super swollen lymph nodes in the armpit of the vaccinated arm? This was a sign that the T and B cells were migrating to the local lymph nodes of the armpit to exchange genetic viral information in preparation for memory B cell development. In the germinal center of these lymph nodes, the antigenic material (protein fragment of the virus) is exchanged and understood immunologically. One fate of this activity is critical. These B cells will go through divisions deeper in the germinal center of the lymph node (think of the rings on a tree moving closer to the center). With each division the B cell adds a mutation to the B cell receptor which mirrors the virus with minor alterations in the anticipation that the virus will mutate as well.

Think about this. Our immune systems evolution coincided with the knowledge that pathogens mutate over time so we do the same thing. The process is called somatic hypermutation whereby the B cells have affinity maturation that allow them to specialize to viral or pathogen structures for future recognition. There are two different types that predominate over time. The basic memory B cell which has a poly reactive memory to a pathogen allows for a lot of flexibility in case of pathogen mutation. The long lived plasma cell is a more high affinity B cell that has more tightly bound antigen recognition and therefore aggressive antibody targeting to a specific previously seen virus.

Memory B cells hide in the tonsils, lymph nodes, spleen, bone marrow and in the blood stream plotting there next attack like a hiding snake in the off chance that a SARS2 (pick your greek letter) mutation variant comes to play. The human B cell variants are ready and poised to get a head start at the viral killing game.

It is a beautiful thing and the major reason behind my belief that we are ok over time with SARS2 if we are either vaccinated or had natural disease and are practicing high quality living that reduces the big co-morbid diseases.

2) "COVID-19 presentation varies widely between individuals, ranging from asymptomatic to life-threatening infection. Several host and viral factors have been shown to influence disease penetrance and severity. In addition, the infectious dose has also been speculated to have a role. Dabisch et al. show in a SARS-CoV-2 challenge study of 16 cynomolgus macaques that the infectious dose indeed influences symptom development and seroconversion. They used aerosolized virus at different concentrations and found that low doses could lead to seroconversion and virus replication in the respiratory tract without symptom development, such as fever, whereas higher doses produced fever, which suggest that low infectious doses might be associated with asymptomatic infection." (Hofer J. 2021)

This is a really important study! It was long suspected that dose and time of exposure were the major risk factors for a bad outcome from SARS2. Now we have concrete data to the affirmative. Super spreaders in a 1 hour church or meeting event could cause significant disease burden whereas people passing you on the street are not the issue. Yet again, we see science proving how ridiculous the current masking rules are for indoor dining where a mask is required to walk to a bathroom, but sitting without a mask while dining is low risk. This policy never made sense and still does not.

For more on the poor state of CDC mask guidance, here is a great opinion piece in the Washington Post by Joseph Allen. He states: "The Centers for Disease Control and Prevention’s recommendations for mask-wearing in areas of “substantial” or “high” spread of covid-19 have resulted in many businesses and universities requiring everyone to wear masks indoors — even if everyone is vaccinated.
This makes no sense. Not only does it rely on flawed metrics to estimate the impact of community spread, but also it ignores all the evidence that vaccines work to limit the spread of the virus."

Common sense is being hidden by political agendas.

3) There was a significant reduction in routine childhood vaccination during the pandemic due to lost visits. (DeSilva et. al. 2021) This is a potential recipe for a resurgence of a previously controlled infection. If your child is behind on any of the routine vaccines of childhood, catch them up to keep herd immunity strong.

4) ZDoggmd has a great video with Monika Gandhi on COVID and many topics related. I highly recommend this video or listen to it in audio. (Link) They discuss the ridiculous messaging that occurred throughout the pandemic. They go into the reality that natural immunity is useful and there is very good science behind T and B cell activity in those who had natural infection. They discuss the massive benefits for adults being vaccinated and the fact that the delta and other variants are not causing major issues to the vaccinated. Dr. Gandhi makes a clear case for how the CDC should be publishing the demographics of the vaccine breakthrough deaths and hospitalizations in order to prioritize vaccine boosters based on need and not a willy nilly executive/CDC order without much logic. The world still needs vaccine and the hot beds of attack in foreign nations are where the variants have come from making blanket US booster statements illogical. The messaging has undermined the entire vaccine effort at the highest levels of government. They discuss so much more regarding what the media and policy makers have completely botched throughout the pandemic leading to the US being one of the worst vaccine adopters globally despite making the best vaccines and having the best access to them. What a mess of epic proportions.

5) "We describe three adolescent and young adult patients who had confirmed or probable COVID-19 infections early on during the pandemic and were referred for evaluation to the Chronic Fatigue Clinic at the Johns Hopkins Children's Center. All patients reported orthostatic intolerance symptoms within the first 2 weeks of illness, and 10-min passive standing tests were consistent with postural tachycardia syndrome. After 6 months of illness, all three patients met criteria for ME/CFS. Clinical features of interest included strong histories of allergies in all three patients, two of whom had elevations in plasma histamine. Each demonstrated limitations in symptom-free range of motion of the limbs and spine and two presented with pathological Hoffman reflexes. These comorbid features have been reported in adolescents and young adults with ME/CFS." (Petracek et. al. 2021) This is a case series that is starting to shed some light on the after effects of Covid19 in a subset of adolescents that developed chronic fatigue like symptoms. They have some features physically and by serum testing that are similar to ME/CFS. Histamine levels greater than 1.8 usually in the 3 to 4 range were noted. This is based on the allergic phenotype found here. The positive Hoffman sign and decreased range of motion of the upper extremities is also consistent with CFS. A Hoffman's sign is performed when a provider snaps or flicks the nail of the middle or 4th finger eliciting a reflex where the thumb and first finger flex in response.

Long COVID is likely to be CFS triggered by SARS2 and treatment will follow suit as is done with CFS patients.

6) "Following a peak at day 15-28 post-infection, the IgG antibody response and plasma neutralizing titers gradually decreased over time but stabilized after 6 months. Plasma neutralizing activity against G614 was still detected in 87% of the patients at 6-15 months. Compared to G614, the median neutralizing titers against Beta, Gamma and Delta variants in plasma collected at early (15-103 days) and late (9-15 month) convalescence were 16- and 8-fold lower, respectively. SARS-CoV-2-specific memory B and T cells reached a peak at 3-6 months and persisted in the majority of patients up to 15 months although a significant decrease in specific T cells was observed between 6 and 15 months." (Marcotte et. al. 2021)

More data on post infection natural immunity that persists for much longer than reported by some sources.

7) "Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the UK to accelerate population coverage with a single dose. At this time, trial data was lacking, and we addressed this in a study of UK healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a sub-study of 589 individuals, we show that this single dose induces SARS-CoV-2 neutralizing antibody (NAb) responses and a sustained B and T cell response to spike protein. NAb levels were higher after the extended dosing interval (6-14 weeks) compared to the conventional 3-4 week regimen, accompanied by enrichment of CD4+ T cells expressing IL2. Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective, immunogenic protocol." (Payne et. al. 2021)

The Institut National de Santé Publique du Québec states that the best post vaccination antibody response was when the second dose was delayed by up to 16 weeks. For example, the study revealed that the Oxford-AstraZeneca vaccine was 47 per cent effective at preventing infections when the second dose was given three to four weeks after the first, as recommended by the manufacturer. But that efficacy jumped to 92 per cent when the second dose was administered at least 16 weeks after the first. (Serebrin J. 2021)

Further high quality data that we should be extending the dosage range between the two dose regimen for mRNA vaccines. Again, we see study data showing more robust responses for those previously infected and recovered plus one vaccine dose. We all need to be consumers of data before making choices on dosing regimens that are blindly being stuck to despite better data globally. The goal is to prevent hospitalization and death not all illness which is impossible. Therefore, we need to iterate protocols for max antibody responses from vaccination with or without prior infection.

Layer your protection,

Dr. M

Antos Infect Dis Reports
Hofer Nature Reviews Microbiology
DeSilva JAMANetwork
Petracek Frontiers in Medicine
Marcotte MedRxIV
Payne Cell
Serebrin CBC
Valcarce Breastfeeding Medicine
Schmidt Nature
Loske Nature Biotechnology
Fischer MedRxIV
Block British Medical Journal
Scott British Medical Journal
CDC MMWR
CDC Variants Page