July 5th, 2021

 Latest numbers google/CDC

Most states are at a steady state with vaccinations and disease for SARS2. There does not seem to be any further movement on the vaccine front or the significant infection front. There are some pockets of disease in poorly vaccinated communities.

The vaccines continue to be effective against all of the variants including Delta.

As it stands today, the United States has had 33.7 million known cases and almost 605,000 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.

 

Mathematically, you now have a 99.9998% chance of survival once vaccinated.

This is much safer than driving a car!

 

Coronavirus Update 39

 

Quick hits

1) Repeat with new information as an important follow up on MIS-C, multi inflammatory syndrome - c., from 2 weeks ago. Remember that in children, MIS-c is associated with poor intestinal function from a microbiome perspective coupled to genetic weaknesses in immune suppression of chemokine CXCL9 post inflammation. Research from the lab of Dr. Alessio Fasano has shown direct evidence of intestinal permeability in children with multi inflammatory syndrome - c:

The authors found that children, unlike adults, the SARS2 virus decides to take up residence in the intestines and replicate there. The virus can be found in the child's stool via testing. This is a unique finding to children as the intestine is not known to be a harboring site for the virus in adults. The expert researcher on this paper, Dr. Fasano, has extensive knowledge of the function of the intestinal mucosal lining and the fact that the cells are held together by tight junctions made up of different proteins forming a semi impermeable membrane. This becomes very important in this case because in this study they found out that a protein zonulin, known to open these junctions, was elevated in the MIS-c children. This indicates that the intestinal integrity has been compromised. They further solidified this case by showing that the SARS2 spike protein "leaked" through this formerly impermeable area into the blood stream. The spike protein then caused an elevation in immune activity in the blood stream consistent with a cytokine storm. The work of Dr. Ed Behrens' group added to this data by showing that the MIS-C children could not turn off the chemical signal for post viral exposure immune enhancement leading to runaway immune inflammation.

What is most interesting in these rare and susceptible children is that they see the virus in their respiratory tract, kill it and move on with little to no symptoms only to show up in clinic 2-4 weeks later with MIS-c owing to this shift of viral replication to the intestine after primary viremia/infection.
• The paper notes that there is increasing knowledge that the intestine serves as ground zero for SARS-2 COVID disease in adults and that in severe cases, microbial dysbiosis (abnormal bacterial makeup) and disruption of the gastrointestinal barrier drive inflammatory activation.
• MIS-C in children is delayed for weeks after initial infection when the virus is no longer found in the nose/respiratory tract making the source of the virus a different replication location in MIS-C.
• They showed that weeks after initial infection, they could isolate RNA for SARS2 in the intestine. There the virus causes intestinal inflammation and permeability leading to spike proteins leaking into the blood stream triggering the inflammatory immune response leading to system wide damage.
• Most therapies including steroids and IVIG (pooled immune globulin) are not clearing the spike protein from the blood pointing to the inability of current therapies to address the virus at the gut level as they are only addressing the downstream inflammation not the upstream generator of inflammation.
• In the study, in one 17 month sick child, they used Larazotide, a zonulin antagonist, an investigational therapy used in this case to block the zonulin peptide that was increasing the intestinal tight junction permeability looking for a reduction in spike protein in the blood and a corresponding inflammatory reduction. This occurred as hoped and clinical resolution occurred. (Yonker et. al. 2021)

Unpacking all of this for MIS-C:
• This is clearly a disease occurring in individuals with prior co-morbidities putting them at risk for baseline inflammation.
• There is a genetic predisposition in some individuals to be missing a gene to suppress the immune inflammatory response once it starts.
• Dysbiosis, poorly balanced intestinal bacteria, is a risk factor for MIS-C and dysbiosis is caused by chronic poorly chosen lifestyle decisions, especially diet.
• We cannot change a genetic risk for a negative outcome but we can absolutely change our decisions that promote dysbiosis and chronic health decay.

Yet again, we see data pointing to our own personal control of our health outcomes. We can as parents make the following decisions to reduce our risk of MIS-C for our children:
1. No matter what has happened in the past, clean up your child's diet by switching to an Anti inflammatory diet, Whole 30 diet  diet or at the least a no processed whole food diet of predominantly fruits and vegetable matter. A highly processed modern diet is the most important antecedent trigger of dysbiosis and intestinal permeability.
2. If you plan to have a child soon, breastfeed your infant from birth and practice healthy weight gain during pregnancy to set the stage for a healthy child's microbiome. The prepregnant time is a perfect time to practice an anti inflammatory diet.
3. Get adequate sleep based on age requirements. For most kids, that is 8 to 10 hours nightly. This will help reduce sleep deprived immune activation.
4. Practice chemical and toxin avoidance by avoiding the consumption of unnecessary drugs that affect the gut including antacids, antibiotics, non steroidal medicines. These medicines will negatively affect intestinal microflora balance promoting dysbiosis.
5. Practice mental health stress reduction through prayer, meditation, art therapy, counseling and more.
6. Exercise and move often stimulating gut motility and evacuation which prevents constipation and small intestinal bacterial overgrowth.
7. Link to many articles on healing the gut biome: link

 

2) Variants - SARS2 Version B 1.617.2 delta is emerging as a new trouble maker. First seen in India in December of last year, it is rapidly spreading in the United Kingdom and the western states of the United States. Early data for the delta variant is showing increased transmissibility (between 40% and 60% higher than the original strain) and maybe slightly more morbidity in the unvaccinated which is yet under study. The mRNA vaccines appear to be working quite well with the Pfizer-BioNTech vaccine showing 88% efficacy against symptomatic disease from the delta variant after 2 doses. (UK.Gov)

National Geographic has a comprehensive article on the delta variant. LINK

In the Lancet we see new data on the delta variant in Scotland. It appears to double the risk of hospitalization versus previous circulating variants in the unvaccinated population. (Sheikh et. al. 2021)

Still zero evidence that the delta variant is more problematic to children at any age.

3) More data as to why we are seeing a flatlined curve despite a more transmissible variant circulating in the US is noted here: "In this investigation we examined the magnitude, breadth, and durability of SARS-CoV-2 specific antibodies in two distinct B-cell compartments: long-lived plasma cell-derived antibodies in the plasma, and peripheral memory B-cells along with their associated antibody profiles elicited after in vitro stimulation. We found that magnitude varied amongst individuals, but was the highest in hospitalized subjects. Variants of concern (VoC) -RBD-reactive antibodies were found in the plasma of 72% of samples in this investigation, and VoC-RBD-reactive memory B-cells were found in all but 1 subject at a single time-point. This finding, that VoC-RBD-reactive MBCs are present in the peripheral blood of all subjects including those that experienced asymptomatic or mild disease, provides a reason for optimism regarding the capacity of vaccination, prior infection, and/or both, to limit disease severity and transmission of variants of concern as they continue to arise and circulate."(Lyski et. al. 2021)

4) A disturbing study from MedRxIV is showing that mild to severe cases of Covid are causing relatively similar issues in the brain with tissue loss. This is not a good thing as we do not do a good job of regrowing brain tissue once damaged. They looked at 394 patients and 388 controls who had received a brain scan before the pandemic had affected them and then after developing the illness. Only 15 of the 394 patients required hospitalization. They found a significant loss of brain grey matter especially in the regions related to taste and smell. (Douaud et.al. 2021)

5) The mRNA vaccines are working to help unvaccinated individuals. "Here, by analyzing vaccination records and test results collected during the rapid vaccine rollout in a large population from 177 geographically defined communities, we find that the rates of vaccination in each community are associated with a substantial later decline in infections among a cohort of individuals aged under 16 years, who are unvaccinated. On average, for each 20 percentage points of individuals who are vaccinated in a given population, the positive test fraction for the unvaccinated population decreased approximately twofold" (Milman et. al. 2021)

Assuming this data set is verified in future analysis, which is likely, and we know that we are at 50% plus vaccination rates in many if not most communities, we then we have a five fold or 500% reduction in disease transmission among the under 16 year old age range. This is playing out clinically in the office as we are seeing rare COVID cases in all children since late April when vaccinations hit a community high. This, yet again, teaches us how effective vaccination is at stopping mass disease transmission on a population level and why it is so important.

6) Long lasting memory is happening: remember that the immune system is poised to respond to new but similar protein structures in viruses through an elegant system of memory. When a virus like SARS2 has the ability to mutate it's RNA sequence and make variants that provide it an advantage for transmission or survival we must counteract this action in a similar way. This is exactly what happens. Our immune system has the ability, once it has seen the virus, to select for specific high affinity antibodies against SARS2. Then the cells that make these antibodies go and hide dormantly in the bone marrow and lymph tissues with expressed goal of activating at lightning speed if SARS2 shows up again even with a variant mutation. (Palm et. al. 2019)

This is the principle reason behind why the variants are offering no major risk to the previously infected or vaccinated Americans. This was the scariest part of the pre vaccine response era for me. Now that we have months of data that the mutations are not thwarting our amazingly smart immune system, we can all breath easier and live life despite what some out there are saying about the variants. Until we see a variant that is circumventing the long lived plasma cells or memory B cells, I am going to live a healthy life without fear.

7) Big study from the UK regarding COVID spread at large events is very reassuring. 58000 spectators at multiple events ended up leading to only 28 Covid cases. This is further reassuring news that the vaccinations coupled to individuals with prior infection have provided a viral reproductive buffer at mass events. (BBC) It is time to return to stadiums and concerts.

8) Is prior infection from SARS2 protective. To date most of the data says yes, especially from severe disease. Now from a new study, Dr. Sheehan and colleagues report the following: "Of those with initial negative testing, 5449 (3.9%) were subsequently positive and 3191 of those (58.5%) were symptomatic. Protection offered from prior infection was 81.8% and against symptomatic infection was 84.5%. This protection increased over time." (Sheehan et. al. 2021) This is inline, albeit slightly less, than vaccination.

All of the studies keep pointing to quality immunity post vaccination or disease. With the memory cells also showing robust responses in multiple studies, we are in good shape for a while. How long is still a work in progress, but I am thinking in terms of years not months. I will be amazed if we will need a yearly booster like the influenza vaccine. Likely every 3 to 7 years or even 10 years like tetanus. These are outright guesses though.

9) In a cool article about the physics of SARS2 aerosol movements in the lungs, we see that 65% of the viral particles reach the distal lung tissue where the oxygen is exchanged and that the right middle and upper lung are the areas most affected. (Islam et.m al. 2021) The SARS2 virus is 120 nanometers in size making it extremely small and transmissible to the distal lung tissue where it can do the most damage. The predilection for the right lung is clinically useful as that makes the focus of therapy in the ICU there.

10) If you have had confirmed Covid infection, then one vaccine dose is enough of a booster to have fantastic immunity and 100% prevention of severe disease. Many European countries are no longer recommending 2 doses after confirmed illness. (Dolgin E. 2021)

11) Preschool children with asymptomatic or mildly symptomatic Covid disease are mounting robust immune responses at 8 months post infection. (Cruz et. al. 2021)The data continues to show us that young children are getting exposed and clearing the virus rapidly with little to no long term problems and great immunity to date.

 

Happy 4th of July,

Dr. M

CDC MMWR
CDC Variants Page
UK Government COVID
Sheikh Lancet
Lyski MedRxIV
Douaud MedRxIV
Milman Nature Medicine
Palm Frontiers in Immunology
Sheehan Clinical Infectious Diseases
Dolgin Nature
Cruz Pediatrics
Islam Physics of Fluids