October 11th, 2021

The 4th wave is over in North Carolina.

If you have had 2 doses of an mRNA vaccine, you have a very very small risk of a significant hospitalization and almost no chance of 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 44 million known cases and over 711,000 deaths.

There is still no change in the knowledge that more than 80% of deaths are skewed toward the over 55 age group and 94% of all deaths occurred in a person with a co-morbid chronic health disease. More biological antibody medicines are on the horizon that may along with a mixture of vitamin A , D, zinc, quercetin and melatonin be employed for a safe resolution to COVID19. 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?

Are you in favor of blinded population based genomic studies to define disease risk?

80% said Yes

Are you worried about bad actors in genetic analysis?

70% said Yes

 Coronavirus Update 46

 Quick Hits -

1) Breastfeeding is passing passive IgG and IgA antibodies against SARS2 to the newborn after maternal natural infection as well as post vaccination. This small 22 mother study showed peak antibody levels 10 days after the second vaccine dose which is expected based on plasma levels for all vaccinees responses. (Valcarce et. al. 2021) How long these antibodies persist and how well they protect remains to be studied. Anecdotaly though, we have had many covid positive mothers deliver in our hospital. No mother to child transmission has occurred to my knowledge. Thus, it is highly likely that natural infection and vaccine alike are useful for disease prevention for a few months at least for the newborn.

2) With children rarely falling severely ill to SARS2/Covid, the question remains as to why some are dying and with incredible inflammation when they do? 480 children have succumbed to the virus since the pandemic started. It leads to the hypothesis of genetic immune mutations allowing for an overreactive immune response or an under reactive viral killing mechanism or both. We have already discussed the work of Drs. Fasano and Behrens in previous newsletters pointed to intestinal dysbiosis and mutations in repressing cell immune signals like CXCL9. Now we see a case report in Nature, "Among children, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are typically mild. Here, we describe the case of a 3.5-year-old girl with an unusually severe presentation of coronavirus disease (COVID-19). The child had an autoinflammatory disorder of unknown etiology, which had been treated using prednisolone and methotrexate, and her parents were half cousins of Turkish descent. After 5 days of nonspecific viral infection symptoms, tonic-clonic seizures occurred followed by acute cardiac insufficiency, multi-organ insufficiency, and ultimate death. Trio exome sequencing identified a homozygous splice-variant in the gene TBK1, and a homozygous missense variant in the gene TNFRSF13B. Heterozygous deleterious variants in the TBK1 gene have been associated with severe COVID-19, and the variant in the TNFRSF13B gene has been associated with common variable immunodeficiency (CVID). We suggest that the identified variants, the autoinflammatory disorder and its treatment, or a combination of these factors probably predisposed to lethal COVID-19 in the present case." (Schmidt et. al. 2021)

As time progresses, I suspect that most infectious diseases that kill children will be isolated to an understanding that genetic immune weaknesses are the pathway to death when coupled to lifestyle triggers of immune inflammation which we have discussed for years. I think of genetic defects in the MAC complex of the complement cascade of immune activity and death from meningococcal disease. Time will answer all of these perviously tragic unknowns.

3) New antiviral pill may be on the horizon. Molnupiravir is a drug that induces mutations in the viruses genome causing an inability of the SARS2 virus to replicate effectively. Phase 2 trials showed a large reduction in viral identification by testing in treated patients. (Fischer et. al. 2021) Now there are reports from Merck that the drug in phase 3 trials is cutting death rates in half for hospitalized patients. This, if proven true, will be very welcome news as there are no really high quality treatments available for reducing death,

While this drug may or not pan out and I truly hope that the data is true, one thing is for sure, changing your lifestyle choices will dramatically reduce all cause mortality over time and vaccination cuts death risk even better than any drug ever will.

4) Unfortunately and fortunately, almost 1/3 of the US has had natural infection. Why is that not being discussed in a positive way for immunity moving forward? In a well written opinion piece in the British Medical Journal, Jennifer Block raises many important questions regarding the illogical approach that the United States has taken regarding individuals with natural immunity. It is worth your time to read the whole piece. She asks very important questions. Why aren't we counting natural infection like a vaccine or at minimum offer one dose of mRNA vaccine 3 months post illness for full immunity comparable to no illness and two vaccines? The data clearly supports this truth. Europe and Israel are using much more logical approaches to these questions. Here some excerpts from the piece:

"As more US employers, local governments, and educational institutions issue vaccine mandates that make no exception for those who have had covid-19, questions remain about the science and ethics of treating this group of people as equally vulnerable to the virus—or as equally threatening to those vulnerable to covid-19—and to what extent politics has played a role." "But the studies kept coming. A National Institutes of Health (NIH) funded study from La Jolla Institute for Immunology found “durable immune responses” in 95% of the 200 participants up to eight months after infection. One of the largest studies to date, published in Science in February 2021, found that although antibodies declined over 8 months, memory B cells increased over time, and the half life of memory CD8+ and CD4+ T cells suggests a steady presence""In Israel, researchers accessed a database of the entire population to compare the efficacy of vaccination with previous infection and found nearly identical numbers. “Our results question the need to vaccinate previously infected individuals,” they concluded.""President Biden left no room for those questioning the public health necessity or personal benefit of vaccinating people who have had covid-19: “We have a pandemic because of the unvaccinated ... So, get vaccinated. If you haven’t, you’re not nearly as smart as I said you were.”"

"A large study in the UK and another that surveyed people internationally found that people with a history of SARS-CoV-2 infection experienced greater rates of side effects after vaccination. Among 2000 people who completed an online survey after vaccination, those with a history of covid-19 were 56% more likely to experience a severe side effect that required hospital care." (Block J. 2021)

Read the last few paragraphs as well. Very informative. For me, this excellent discussion again puts the federal messaging in a bad light. Why are we not following the logic of good science as stated in this piece and all of the published data presented since the beginning of the pandemic? Why the rigid approach that alienates a large swath of intelligent Americans? I have seen many people who were infected with natural COVID have a really bad reaction to dose number 2. This entire process of vaccination and immunity understanding needs to be reassessed lest the federal government and the CDC lose more credibility than they already have. Science doesn't lie, it just improves upon itself until answers become more clear. Politics is a whole different animal altogether.

5) Boots on the ground - No increase incidence of MIS or deaths in children noted by my friends in Charlotte, Charlottesville, Raleigh and Philadelphia. There are many more cases in children which is expected with a more infectious viral variant. Adult disease continues to be mostly in unvaccinated individuals with a co morbidity or vaccinated individuals over 65 years with comorbid disease. The theme of inflammation and age continues true.

6) The case for universal boosters. The authors write: "the primary objective of covid-19 vaccines is to protect against severe illness rather than infection, and multiple well designed studies have found sustained vaccine effectiveness against severe covid-19 for most adults. One large UK study, published as a preprint, using a case-control design based on PCR results showed that very high levels of protection against severe disease continued beyond five months after vaccination, especially among people who have no serious underlying conditions." (Scott et. al. 2021) This is another well thought through and written article that is worth your time to read. The case for universal boosting has never made sense to me and again seems politically driven and not based on sound science. The boosters make complete sense for at risk groups.

7) A nice article in the Conversation by Jessica Bernard on the effects of SARS2 on the brain can be found at this link. It goes through much of the data that I have already presented on brain tissue loss and what that means.

8) In an interesting study looking at predictions of reinfection in a Covid endemic state of living, the authors stated: "These data provided a means to estimate profiles of the typical antibody decline and probabilities of reinfection over time under endemic conditions. Reinfection by SARS-CoV-2 under endemic conditions would likely occur between 3 months and 5·1 years after peak antibody response, with a median of 16 months. This protection is less than half the duration revealed for the endemic coronaviruses circulating among humans. For SARS-CoV, the 5–95% quantiles were 4 months to 6 years, whereas the 95% quantiles for MERS-CoV were inconsistent by dataset." (Townsend et. al. 2021)

Although this is predictive modeling, it is likely in line with what we will see as circulating common cold coronaviruses are able to reinfect people with relative ease and frequency. Thus, as has been said many times, we need to get busy living with this virus and life in general. My only response to this data set is this. If, and likely true, SARS2-covid19 is here forever, we have only two really good choices moving forward: 1) get vaccinated, 2) practice basic lifestyle choices that are pro longevity which we have discussed forever.

I do fear that many Americans will not follow #2 and that as with the flu, we will see many extra deaths annually from covid for centuries to come.

9) We have known for over 18 months now that kids are at significantly lower risk of hospitalization and death. 710000 deaths in older populations compared to 480 children. Why? We have posited for a long time that it was early recognition and killing based on detected antibodies in children as well as the reduced inflammatory burden of children because of age. Now we see a nice mechanistic paper in Nature pointing to an increased ability to see and kill the virus at the earliest stages in the nose and respiratory tree.

"Children have reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and a substantially lower risk for developing severe coronavirus disease 2019 compared with adults. However, the molecular mechanisms underlying protection in younger age groups remain unknown. Here we characterize the single-cell transcriptional landscape in the upper airways of SARS-CoV-2-negative (n = 18) and age-matched SARS-CoV-2-positive (n = 24) children and corresponding samples from adults (n = 44), covering an age range of 4 weeks to 77 years. Children displayed higher basal expression of relevant pattern recognition receptors such as MDA5 (IFIH1) and RIG-I (DDX58) in upper airway epithelial cells, macrophages and dendritic cells, resulting in stronger innate antiviral responses upon SARS-CoV-2 infection than in adults. We further detected distinct immune cell subpopulations including KLRC1 (NKG2A)+ cytotoxic T cells and a CD8+ T cell population with a memory phenotype occurring predominantly in children. Our study provides evidence that the airway immune cells of children are primed for virus sensing, resulting in a stronger early innate antiviral response to SARS-CoV-2 infection than in adults." (Loske et. al. 2021)

This data and all the data given to date has to be part of the calculus behind any parents decisions regarding their younglings moving forward.

 

Keep thinking,

Dr. M

 

Valcarce Breastfeeding Medicine
Schmidt Nature
Loske Nature Biotechnology
Fischer MedRxIV
Block British Medical Journal
Scott British Medical Journal
Townsend Lancet Microbe
Loske Nature Biotechnology
CDC MMWR
CDC Variants Page