September 6, 2020
Latest numbers show that we have seen massive drop-offs in deaths and cases in all of the formerly hard hit areas. The previously untouched midwest is seeing increased case volume. North Carolina peaked on July 23rd. More than 80% of deaths are skewed toward the over 55 age group and 94% of all deaths occurred in a person with a comorbid chronic health disease. 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.
NC death cases
In a nutshell, a paper written by Dr. Garvin and colleagues reviewed the outcome of the data crunched by the supercomputer at Oak Ridge National Laboratory regarding COVID19 and came up with an excellent unifying theory for COVID 19's symptom complex and death outcomes. It is not truly a cytokine storm but also a bradykinin storm.
This is an event where excessive amounts of bradykinin are released into the circulation and local tissues in response to the SARS2 virus. Bradykinin is a chemical that naturally induces blood vessel dilation and permeability leading to local leakage of fluid in to tissue spaces during a healing process that requires clotting or inflammation. This allows immune and inflammatory mediators of healing to be mobilized to areas of infection or injury. Under normal circumstances, the dilation and leakage are all self limited and result in an inflammatory response, resolution and complete recovery.
According to the new hypothesis, the SARS2 virus induces excessive volumes of bradykinin all over the body leading to leakage of increased amounts of fluid and cytokines into healthy tissue areas which leads to more inflammatory cytokines infiltrating the tissue and compounding the fluid based inflammatory response that essentially drowns a sick patient. I will stop here in this section. In a coming newsletter I will produce a unifying pathophysiological theory based on all of the excellent research to date.
The new news:
1) Why does lightning strike the young rarely? We now have a glimpse into why some young healthy people are succumbing to COVID19 on extremely rare occasions - genetic weakness immunologically. In the Netherlands, there was an analysis of two sets of brothers who suffered significant disease morbidity and one death from COVID19. They found out that the men, aged 21 to 32 years of age, had genetic defects in the X linked TLR7 gene which encodes for the pattern recognition receptor known as toll like receptor 7. This receptor is critical in recognizing a pathogen like coronavirus early on during an infection and then sending out a warning signal called an interferon which in turn calls in the immune system on a broader scale to mount a vigorous killing response. (Van der Made et. al. 2020)
I am convinced that we will find out over time that these one off lightning strikes for the 20 to 40 year old healthy individuals are all or mostly related to genetic immune weaknesses of surveillance, recognition and killing of pathogens. This is unfortunately Darwinian.
Another reason to live every single day to its fullest!
2) Men are at higher risk for many reasons including: a) earlier onset of lifestyle related diseases of aging that put a person at risk for COVID19. b) men and women have different immune makeups related to childbearing (Selmi C., Gershwin M. 2019) c) as above with the brother study, "It turns out that there are over 60 genes associated with immune function on the X chromosome," Klein says. Some are involved in the production of interferons, key modulators of the body's response to viruses. "My group and others have shown that females show greater expression of some of these genes than do males," Klein adds, "and this can have functional significance." (Wallis C. 2020)
Essentially, women have more robust innate immune systems for viral and bacterial surveillance during the childbearing years that seems to change to mirror men after menopause. This makes complete evolutionary sense as a mother's immune system during pregnancy has to shift in order to tolerate the genetic makeup of the child which is 50% father based. This would not work if the T Helper cell profile remained in an attack mode, i.e. TH1/17. Therefore, the female physiology evolved to use X chromosome genes and estrogen and prolactin hormones to drive immune changes that allow for vigorous immune pathogen surveillance but not attention to the child's genetic foreignness.
Female physiology is truly beautiful!
3) Lockdowns are not useful and take a high toll economically, mentally and for the future of our children. A second high quality analysis of lockdowns and the lack of benefit has been published in the Wall Street Journal this month. The biggest concern in a pediatrician's eyes will always be the negative effects on a child's wellbeing and future prospects. This article does a great job looking at these and many other aspects of the poorly decided lockdown strategy. I find it even more fascinating that the CDC even had a 2017 community mitigation guideline for severe pandemic flu stating that stay at home orders were not recommended.
In my opinion, we are now at the point in this pandemic where we have enough knowledge to conclusively recommend that masks are useful for avoidance of exposure. Limiting prolonged poorly ventilated indoor social activity is massively beneficial. I am now very conscious of visits that are pushing the 20 to 30 minute mark in a closed clinic room. Washing hands for 20 seconds multiple times a day has high efficacy for transmission reductions.
Most importantly, we must encourage everyone to eat healthfully, sleep 8 hours nightly, exercise daily, avoid toxins and be at peace mentally. Here is where the rubber truly meets the road for death prevention.
4) Racial inequalities continue to play out with higher death rates among minority individuals. There are multiple reasons behind this unfortunate reality the least of which is actually genetics. According to the statistics, structural racial inequalities are driving the differences: more crowded living environments increasing viral spread and load, more immune dys-regulating stress increasing viral survival and promoting systemic inflammation, more food deserts/poor nutritional support coupled with unsafe environments reducing physical activity promoting inflammatory based chronic disease which is a primary risk of death from COVID19, more toxin exposure in low paying factory jobs and poor quality living environments driving inflammation and much more.
These issues are profound and require a concerted societal and governmental effort to reverse for this and the next generation. We must act from the grassroots level on up. We must treat everyone with respect and dignity as we help our fellow American heal the lifestyle wounds that place them at risk.
5) Over a 2 month period in Rhode Island, they found that there were 30 COVID 19 transmissions that occurred in children in child care settings out of 18,945 children statewide. There was an additional 22 teachers and adults that tested positive during the same time period. This is another study showing the significantly rare rate of transmission in child care settings. (MMWR report) If these statistics held all year, a big if, that would mean 180 childhood cases in a year across the state or 1% over that years time frame. More data to ponder over risk of schools and day care environments. The lack of quality school education is a massive known risk. These data sets continually point to getting the children back in school.
6) Vitamin D deficiency data again. In the Journal of Endocrinological Investigation, Dr. Carpagnano and colleagues looked at vitamin D status in ICU admitted adults and respiratory failure. They found in a sample of 42 patients that severely deficient vitamin D status during hospitalization was associated with higher mortality and worse respiratory disease. The higher the vitamin D level the better the outcome. (Carpagnano et. al. 2020) While this does not prove causation, it does make one believe that either vitamin D status is a proxy for overall health or it is mechanistically involved in the outcome, or both. I think that the answer is both. We have discussed here many times that obesity and other lifestyle related diseases confer increased risk for vitamin D deficiency and that mechanistically vitamin D is involved in immune function at a macro level.
7) We continue to learn more about immune responses in individuals that are asymptomatic. From a recent Nature article by Rebecca Cox, she writes: "Although spike-specific CD4+ T cells are found in patients with COVID-19, 30-50% of healthy people with no detectable COVID-19 infection also had SARS-CoV-2-specific CD4+ T cells and 20% had CD8+ cytotoxic T cells. These T cells are probably cross-reactive with other HCoVs, but whether they can provide protection from COVID-19 disease remains to be determined. Furthermore, CD4+ T cells and CD8+ T cells specific for SARS-CoV-2 were found in the convalescent phase after mild COVID-19 and these T cells were shown to recognise peptides derived from the viral spike, nucleoprotein and matrix as well as other viral proteins." (Cox et. al. 2020)
See this figure for a pictorial objective of this discussion.
What we are learning is that after a COVID19 infection the immune system may not have IgG antibodies circulating in the blood against COVID as the half life of an IgG antibody is 21 days. But this by no means displays a lack of ability nor immunity to SARS2. It is actually highly likely that these individuals have enough immune recognition to thwart a major infection moving forward. This is another likely reason for the decreasing numbers in all hotspots over time. (Rodda et. al. 2020)
Whether this bears fruit or not, we shall see. The current trend in the former hotspots of the northeast, Florida, Georgia, Louisiana, California and Texas speak to this possibility. However, some hard hit European countries are now seeing increased cases and deaths. We need more time and data to conclude that we are where we think that we are.
8) Asthma continues to not be associated with poor outcomes from COVID19. Dr. Broadhurst and colleagues looked at admissions and intonations and found no difference between asthmatic and non asthmatic patients. (Broadhurst et. al. 2020) This is likely due to the fact that COVID19 is a vasculitic disease more than a pulmonary disease pathogenically.
9) My friend, Dr. Sam Yanuck, shared two profound articles for COVID prevention through sleep sufficiency. The gist is as follows: when we are to sleep adequately, our nighttime pre bedtime physiology has to be that we have low cortisol, high melatonin and high adenosine levels. These same chemicals send a set of signals to the immune system to induce adequate viral fighting T helper type 1 cells and natural killer cells. This in turn causes an uptick in interferons which are critical to get SARS2 under control.
9) Sweden continues to look good without locking down. This makes me smile as it takes incredible guts to do what they did. (Mckinsey Economic Analysis)
10) An excellent 18 minute podcast by Docsmo on the SARS2 vaccines is available here.
For now, using a mask of the surgical type appears to be a great idea to prevent spread. The best idea for survival is still rooted in caring for yourself through healthy eating, adequate rest, exercise and stress reduction.
Knowledge is power,
Dr. M
Smith Medium
Hofman Clin Reviews Allergy Immunology
Ip Wall Street Journal
Van Der Made JAMA
Ellinghaus NEJM
Selmi Expert Rev Clin Immunology
Wallis Scientific American
CDC Death Statistics
MMWR Rhode Island
Carpagnano J Endo Investigation
Cox Nature Reviews Immunology
Rodda Medrxiv
Broadhurst American Thoracic Society
For those who missed the analogy:
After running with a few friends on a sidewalk, a gentleman coming in the other direction walked quite far away with the intent of decreasing his risk of exposure to SARS2 which I found reasonable on the face of it. It brought to mind an analogy to understand risk. It is clear from the data that COVID risk is heavily defined by prolonged exposure to the virus via aerosol droplets, i.e. being in a closed room for 20 plus minutes without a mask with an infected person = bad idea. This is how viral load comes to be a major player.
Star Wars analogy: Imagine that a Jedi is the equivalent to the human that is less than 60 years old and maximizing lifestyle choices for health. In the Star Wars movies, a Jedi is the pinnacle of balance in mental and physical abilities like a well tuned immune system in a human. The clone troopers represent a SARS2 virus particle. Thus, if we imagine a bunch of clone troopers coming to kill the well trained Jedi knight, the outcome is total destruction for the clones. However, if the Jedi is injured through poor choices like not sleeping, eating poorly for a while, drinking too much alcohol or smoking and being stressed out, then the number of troopers needed to win the battle decreases and the outcome can change. As we age, we develop more risks for dysfunctional Jedi abilities leading to less clones needed to beat us.
This is simplistically what is happening with COVID19. The volume of viral particles needed to get into your system and kill you is directly related to your inherent Jedi powers and time spent in the war zone. The more time you spend in the war zone the more clones you will have to kill off. The more time you spend abusing your body, the less viral particles needed to hurt or kill you.
