Volume 12, Letter 35 Coronavirus Update 68 plus other stuff

Omicron US strains: as of August 13th data - variants make up: BA.4 is 5%, BA 4.6 is 5% BA.5 is 89%, and B2.12.1 is 1%. This Covid wave is still inline with volumes from wave three which was delta.

BA 4.6 is a newer sub variant of BA.4. No evidence of any major concern here as it is not outcompeting BA.5

BA.5 is showing no signs of increased disease morbidity.

R0 infectiousness is in the range north of measles: the new reproductive rate is 1 infects 12 which infects 144 which infects 1,728 which infects 20,736 which infects 248,832. That is a very very fast spread rate and likely an underestimate.

Little else to report here. (CDC Variants)

At this point the fundamentals completely point to a world of Covid mitigation based on personal risk tolerance and previous vaccination and/or disease. It no longer makes any sense for the entire population to be asked to change the way they live and exist. The messaging (See number 9 below) remains a struggle for me as people including the heads of major health organizations are pushing for measures beyond what is logical. Messaging continues to be unrealistic regarding Covid for society at large. Why?

1) 95+% of the population has a priori immunity based on vaccination and or viral disease survival making the risk of death for this group very very very low

2) Death rate and hospitalization per infection has plummeted and is no longer coupled to infectious regional volume which remains quite high with BA.5. Death and hospitalization are the only metrics that matter.

3) Morbidity remains tied to personal health risks: age greater than 65, co-morbid disease that has inflammation at it's core (Diabetes, hypertension, coronary vascular disease and obesity)

4) Mental health and the health of the nation's economy are also important and should not be put behind Covid anymore in the pecking order

5) Boosters remain minimally effective for most of us at preventing symptomatic infection and there is excellent evidence that prior infection and/or a 2 dose series of mRNA vaccines provides incredible coverage against death and hospitalization. This is not true if you have a risk factor

6) Too many people have put off healthcare because of Covid fear increasing disease burdens and delayed cancer diagnosis. We need to normalize our environment for most of us

Based on these truths, we need to get back to life as normal.

On that note: the CDC has just released new guidance that is welcome:

·     If you are exposed to Sars2, you no longer need to quarantine at home, regardless of vaccination status - caveat - wear a mask for 10 days and get Covid tested on Day 5

·     If you test positive for Sars2, you should still isolate at home for at least five days followed by 5 days of masking. If you had moderate or severe illness, or are immunocompromised, you should isolate for 10 days

·     Unvaccinated children/students who are exposed to Sars2 will no longer need to test unless symptomatic

·     Social distancing is recommended on a personal risk basis

·     The guidelines around masks — which recommend that people wear them indoors in places where community Covid levels are high — have not changed. (CDC)

Quick Hits and other musings -

1) Intermitent fasting and Covid death risk? This is a key study that reinforces everything that I believe in and what the data has said over the pandemic: restricting your access to food that drives inflammation will have a net positive effect on all cause survival including Covid. From the study: Subjects engaging in periodic fasting (n=73, 35.6%) did so for 40.4±20.6 years prior to COVID-19 diagnosis. The composite outcome occurred in 11.0% of periodic fasters and 28.8% of non-fasters. Other predictors of hospitalisation/mortality were age, Hispanic ethnicity, prior MI, prior TIA and renal failure, with trends for race, smoking, hyperlipidaemia, coronary disease, diabetes, heart failure and anxiety, but not alcohol use. In secondary analysis, COVID-19 was diagnosed in 14.3% of fasters and 13.0% of non-fasters. Conclusions: Routine periodic fasting was associated with a lower risk of hospitalization or mortality in patients with COVID-19. Fasting may be a complementary therapy to vaccination that could provide immune support and hyper-inflammation control during and beyond the pandemic. (Horne et. al. 2022)

The science here is multi fold: 1) fasting removes food from the metabolic and immunological system allowing for random resets in the autophagy of poor quality cells as well as immune enhancement of T and B cell lines. 2) fasting reduces global inflammation and its respective excessive inflamed cells from the circulation. 3) fasting shifts the energy source from carbohydrates predominantly to fatty acids which are known to bind the Sars2 receptor binding domains reducing viral entry 3) repeated fasting boosts basal levels of galectin-3 which has a downstream effect on infectious risk by directly binding to a wide variety of pathogens, activating the innate immune system, increasing the expression of human genes encoding proteins with antiviral capacities which inhibits viral replication. 4) fasting could be removing, albeit temporarily, trigger foods for inflammation like dairy or gluten in non celiac gluten sensitive patients that could have the net effect of reduced systemic inflammation.

I will say this - I have been time restricted feeding for 4 years now. I compress my eating times between 1 pm and the 6-7 pm most days. 1-2 days a week, I am now trying to fast for 23-24 hours. I find that I feel the best with this pattern of food consumption. It is a challenge to get all of my needed calories this way, but so far so good.

2) For how long will we be dealing with repeated infections to Sars2? An interesting article in the Atlantic goes through some of the theories on this topic. (Zhang S. 2022) I fall in the camp that we may see mutations related to infectiousness but not morbidity. However, I suspect that this will not change much. Time will tell.

3) Helminths and disease risk may be a major reason behind Africa's morbidity numbers compared to the industrialized countries globally. From an article in Evolution, Medicine and Public Health: "Suboptimal understanding of concepts related to hygiene by the general public, clinicians and researchers is a persistent problem in health and medicine. Although hygiene is necessary to slow or prevent deadly pandemics of infectious disease such as coronavirus disease 2019 (COVID-19), hygiene can have unwanted effects. In particular, some aspects of hygiene cause a loss of biodiversity from the human body, characterized by the almost complete removal of intestinal worms (helminths) and protists. Research spanning more than half a century documents that this loss of biodiversity results in an increased propensity for autoimmune disease, allergic disorders, probably neuropsychiatric problems and adverse reactions to infectious agents. The differences in immune function between communities with and communities without helminths have become so pronounced that the reduced lethality of severe acute respiratory syndrome coronavirus 2 in low-income countries compared to high-income countries was predicted early in the COVID-19 pandemic. This prediction, based on the maladaptive immune responses observed in many cases of COVID-19 in high-income countries, is now supported by emerging data from low-income countries. Herein, hygiene is subdivided into components involving personal choice versus components instituted by community wide systems such as sewage treatment facilities and water treatment plants." "Emerging evidence indicates that much of the morbidity/mortality associated with SARS-CoV-2 is in fact due to an overly aggressive immune response and ensuing cytokine storm that may be partly autoimmune in nature. In general, in the field of medicine, the presence of helminths is thought to produce an attenuated immune response due to secretion of immunoregulatory molecules, creation of regulatory networks and changes in mucosal surface permeability. However, given that vertebrate immune function evolved in the presence of symbiotic helminths, the field of medicine needs a change in perspective and may benefit greatly by considering the immune response in the presence of helminths to be ‘normal’ and function in the absence of helminths to be hyperresponsive. With this view in mind, it seems intuitive that biota alteration may be, at least in part, responsible for part of the morbidity and mortality associated with SARS-CoV-2 in high-income countries."(Parker et. al. 2021)

Dr. Parker and I sat down in 2021 to discuss this topic with podcast #7, the Macrobiome and Human Health. It is very clear to me that the loss of biodiversity is a major problem in humans whether it is in the bacterial microbiome or with parasites in the intestinal macrobiome. These issues are not going away. Humans are heading toward towards a worsening health state as we continue to take lifestyle choices that are not inline with our genetics and our symbiotic relationships. We are truly becoming polar bears trying to live in the desert. Stay tuned for a little more on this topic next week.

4) In an excellent piece in the Wall Street Journal, we see reams of stats noting major declines in our collective health metrics following Covid disease. Heart disease and stroke incidence has jumped almost 6% from prepandemic volumes. This is not surprising as the mode of SARS2 attack will negatively affect individuals that were already struggling with vascular inflammation. There was also a massive increase in antibiotic resistant bacteria caused by the sheer volume of sick humans requiring antimicrobial therapies for prolonged periods of time. These antibiotics were often inappropriately prescribed to help covid patients out that were not suffering from bacterial disease. Couple this again to the reality that many immunologically unhealthy individuals will remain sick for longer increasing their risk of antibiotic exposure. Lifestyle issues related to stress and depression also went way up including alcohol/drug use, firearm deaths, sexually transmitted diseases and more. And finally, health based prevention testing and vaccinations decreased. Cancer screenings and identification waned leading to later diagnosis and worse disease burdens. (Abbott B. 2022)

5) SARS2 attacks the human in the respiratory tract via the ACE2 receptor which happens to be found in high number in the olfactory epithelium and the sustentacular cells. The SARS2 viral infections causes these smelling cells to be sloughed off leaving the tissue to look like an inflammatory wasteland. There are two scenarios that could occur depending on the pre-infectious inflammatory baseline of the infected individuals as well as the initial virus load. Healthy individuals with or with out a high viral load will likely have a recovery that is fast due to the basal cells regenerating the same cells as were present pre illness.

This recovery may be impaired by several factors:

• Individuals characteristics. Indeed, aged and/or overweight individuals are much more susceptible to COVID-19. The olfactory epithelium integrity declines with age and overweight individual often present an increased basal inflammation state in their tissue which could also impair regeneration. Infection by SARS-CoV-2 of olfactory epithelium already in an inflammation state may facilitate the virus infection efficiency as its receptor ACE2 is overexpressed during inflammation.

• Initial virus load. OSN or olfactory sensory neurons seems to be infected only with higher virus loads. If this infection reaches a certain threshold, it could begin to affect immature OSNs which will impact the regeneration of the olfactory epithelium.

• Invasion of the respiratory epithelium. Part of the olfactory epithelium can be replaced by respiratory epithelium as usually observed in post viral olfactory disorders. It would diminish the recovery from anosmia. (Meunier et. al. 2021)

6) Menstrual changes with Covid were a noted reality for many women. From Science Advances they write: We found that increased/breakthrough bleeding was significantly associated with age, systemic vaccine side effects (fever and/or fatigue), history of pregnancy or birth, and ethnicity. Immune activity and hormonal function are intimately tied together in women. The spike protein of the SARS2 virus is very immune activating making it highly likely that natural disease and the vaccination will have a short term negative effect on menstrual activity and female hormone activity in general. Being transient makes it highly unlikely that it will be problematic.

However, I still have firm beliefs that people that abuse the metabolic system are at higher risk for these issues at baseline and that the viral illness just pushes them over the edge into symptoms. I think of PCOS, polycystic ovarian syndrome, or testicular volumes here. These issues are highly associated with obesity and highly processed diets.

7) Prolonged loss of smell is a risk factor for cognitive decline in post Covid patients. This is likely related to the fact that the virus has attacked the brain in a global way. We know that many of these patients have lost brain cell activity in the support cells of the nasal epithelium. It may be a more global attack on the brain. Time and more research will answer these questions. Folks suffering from cognitive decline should read this paper in the Journal Aging by Dr. Dale Bredesen.

8) PACS or Long Covid is finally getting more granular based on the research. From Dr. Canas and colleagues we see that "two to eight symptom profiles (clusters) were identified, with three recurring clusters. A cardiopulmonary syndrome was the predominant observation, manifesting with exertional intolerance and dyspnoea, fatigue, autonomic dysfunction, tachycardia or palpitations, lung radiological abnormalities including fibrosis, and chest pain. A second common presentation consisted in persistent general autoimmune activation and pro-inflammatory state, comprising multi-organ mild sequelae, gastrointestinal symptoms , dermatological symptoms, and/or fever. A third syndrome was reported, with neurological or neuropsychiatric symptoms: brain fog or dizziness, poor memory or cognition, and other mental health issues including mood disorders, headache, central sensitization, paresthesia, autonomic dysfunction, fibromyalgia, and chronic pain or myalgias. Unsupervised clustering methods identified two to six different post-COVID phenotypes, mapping to the ones described above. "(Canas et. al. 2022)

This information remains very useful for the future of clustering these patterns in order to study them closer for genetic, epigenetic and causative patterns that could lead to better treatments.

9) Here is an example of everything that is wrong with modern media messaging: An article written for the lay public basically stating (without discussing who is at risk) that we should all avoid these 5 places from now on with Covid sub variant omicron BA.5 in play. The author uses Dr. Ulm - "Dr. J. Wes Ulm, Harvard and MIT-trained MD, PhD with a background in bioinformatics, gene therapy, genetics, drug discovery, consulting and education tells us." as the arbiter of truth. "Although BA.5 is spreading like wildfire across the United States, there are ways to try to prevent catching the virus and Dr. Ulm shares five places to avoid and why. Read on—and to ensure your health and the health of others". Here are the five avoidance decisions that we are counseled to make now: 1) Large Indoor Gatherings, Especially if Air-Filtering, Ventilation, and UV Disinfection are Unavailable, 2) Smaller Indoor Gatherings with Close Contact or Inability to Social Distance, 3) Public Transportation, 4) Indoor Gyms or Health Clubs with Poor Ventilation, 5) Outdoor Events in Close Quarters, Especially with Close Proximity to Loudly Yelling or Hollering Voices. (Newgen H. 2022)

Let me get this straight. A virus that is highly infectious unlike anything we have seen in my lifetime and finally not causing significant deaths nationally based on a priori SARS2 exposure plus vaccinations is now necessitating these draconian choices without context of each persons personal health risk. Wow. This virus is likely to be here forever which in turn means that the authors are planning a long term strike against these 5 behaviors to save our culture. In a vacuum where the economy, personal happiness and personal health risk are not accounted for, then this is completely reasonable. Alas, we live in the real world! Current hospitalization rates due to Covid remain very low despite high circulating viral illness. Death and hospitalization drive the way a society exists with a novel virus not circulating viral levels and ivory tower researchers.

The long term consequences of these 5 choices on a national scale if repeated based on every new Covid wave: 1) no more family gatherings indoors! 2) no more concerts or sporting events where you are not 6 feet away from your neighbor who is not allowed to scream 3) forget the gym. If you cannot workout outside and be socially distanced, just stop exercising 4) bankrupt companies by the boatload who used to provide gym services, concerts, events, drove a bus/plane/train/etc.. and anyone working for a company that these 5 rules will hurt. How are these authors mitigating these downstream problems of poverty, mental health struggles, less exercise fitness, decreased social happiness? Where is the common sense education?

What is absolutely lost on many in America remains the true reality that these current viruses and pathogens of the future are here full stop. The absolutely best way to avoid the nightmare of death and morbidity is to take care of your immune self as has been discussed many times to date or can be found in the the newsletter about an Integrative approach to proper health in the COVID era and frankly all future infectious diseases, read this link and this link.

If Dr. Ulm and Heather Newgen would have taken a global perspective discussing 1-5 as mitigation measures for the at risk population while simultaneously discussing global lifestyle decisions that help us all improve our resilience to infectious disease, then I am all in. Unfortunately, this is the messaging that we get instead. Buyer beware as we will continue to see guidance that does not take everyone into account. I find these types of articles very disturbing and very damaging for the collective health of the whole population, especially when they come from a person(s) who represent the highest level of education.

That's all this week,

Dr. M

Horne BMJ Nutrition Prev Health

Zhang The Atlantic

Parker Evolution Med Pub Health

Abbott WSJ

Meunier Frontiers In Physiology

Lee Science Advances

Canas MedRxIV

Newgen Eat This

CDC MMWR

CDC Variants Page

CDC Covid Deaths