November 21st, 2022

The work around Covid research is fading for me. This is now mostly a highly contagious upper respiratory infection for most. The morbidity has faded to a level where we are seeing very limited disease in children and the hospital data remains completely plateaued. Unless there is a dramatic shift in this virus, we are moving toward a world where Covid may be like the other 4 circulating coronaviruses for most of the United States population

Omicron US strains: as of November 19th data - variants make up: BA.4.6 is 4%, BN.1 is 5%, BF.7 is 8%, BA.5 is 24%, BQ.1 is 26%, BQ1.1 is 24%

BA.5 has lost most of the ground it had held for a while to many new Omicron variant offshoots. BF.7, BQ.1 BN.1 and BQ1.1 are very interesting as they are more infectious than BA.5. That remains amazing. If you look at the CDC variants bar graph, it is silly how many new variant Omicron offshoots there are now.

BF.7 and the new BQ variants have mutations in the spike and nucleotide regions of the RNA genome giving them increased infectiousness and immune evasion. Pharmaceutical antibody therapies are no longer working. No higher level of morbidity noted for the vaccinated and previously infected.

None of these VOC's are showing signs of increased disease morbidity.

Little else to report here. (CDC Variants)


Quick Hits and other musings -

1) In a well written article in Time Magazine we see a thorough analysis of the new circulating variants.
Scientists took blood sera from 88 people in five groups (below) and exposed it to the four variants in the lab. Here’s what they found:
• Fully vaccinated and once-boosted people (three total shots of the original mRNA vaccines) had 37- and 55-fold lower neutralization against BQ.1 and BQ.1.1, respectively, than they did against the original SARS-CoV-2 virus, and about 70-fold lower neutralization against XBB and XBB.1.
• Fully vaccinated and twice-boosted people (four total shots of the original mRNA vaccines) had 43- and 81-fold lower neutralization against BQ.1 and BQ.1.1, respectively, than they did against the original virus, and 145- and 155-fold lower neutralization against XBB and XBB.1, respectively.
• Fully vaccinated and twice-boosted people (three shots of the original vaccine plus one Omicron booster) had 24- and 41-fold lower neutralization against BQ.1 and BQ.1.1, respectively, than they did against the original virus, and 66- and 85-fold lower neutralization against XBB and XBB.1, respectively.
• Fully vaccinated people who had received the original booster and who had been infected with BA.2 had 20- and 29-fold lower neutralization against BQ.1 and BQ.1.1, respectively, than they did against the original virus, and 103- and 135-fold lower neutralization against XBB and XBB.1, respectively.
• Fully vaccinated people who had received the original booster and who had been infected with BA.4 or BA.5 had 13- and 31-fold lower neutralization against BQ.1 and BQ.1.1, respectively, than they did against the original virus, and 86- and 96-fold lower neutralization against XBB and XBB.1, respectively.
(Park A. 2022)

The take home is simple: All new omicron based variants are extremely infectious but not really dangerous anymore to immunocompetent people. They are evading prior immunity as well as all vaccines to varying degrees. Morbidity remains very low now. The current bivalent vaccines are not showing any improvement over the ancestral vaccine. Death remains almost zero for all healthy previous infected or vaccinated individuals. This is likely the new norm from here on out.

2) Katherine Eban has written a new thorough piece on the Pandemic origins and it is absolutely worth your time to read. From the article: "Week after week, scientists from those branches chronicled their party-building exploits in reports uploaded to the WIV’s website. These dispatches, intended for watchful higher-ups, generally consist of upbeat recitations of recruitment efforts and meeting summaries that emphasize the fulfillment of Beijing’s political goals. “The headlines and initial paragraphs seem completely innocuous,” Reid says. “If you didn’t take a close look, you’d probably think there’s nothing in here.” But much like imperfect propaganda, the dispatches hold glimmers of real life: tension among colleagues, abuse from bosses, reprimands from party superiors. The grievances are often couched in a narrative of heroism — a focus on problems overcome and challenges met, against daunting odds. As Reid burrowed into the party branch dispatches, he became riveted by the unfolding picture. They described intense pressure to produce scientific breakthroughs that would elevate China’s standing on the world stage, despite a dire lack of essential resources. Even at the BSL-4 lab, they repeatedly lamented the problem of “the three ‘nos’: no equipment and technology standards, no design and construction teams, and no experience operating or maintaining [a lab of this caliber].”

"And then, in the fall of 2019, the dispatches took a darker turn. They referenced inhumane working conditions and “hidden safety dangers.” On Nov. 12 of that year, a dispatch by party branch members at the BSL-4 laboratory appeared to reference a biosecurity breach. Once you have opened the stored test tubes, it is just as if having opened Pandora’s Box. These viruses come without a shadow and leave without a trace. Although [we have] various preventive and protective measures, it is nevertheless necessary for lab personnel to operate very cautiously to avoid operational errors that give rise to dangers. Every time this has happened, the members of the Zhengdian Lab [BSL4] Party Branch have always run to the frontline, and they have taken real action to mobilize and motivate other research personnel. Reid studied the words intently. Was this a reference to past accidents? An admission of an ongoing crisis? A general recognition of hazardous practices? Or all of the above? Reading between the lines, Reid concluded, “They are almost saying they know Beijing is about to come down and scream at them.” And that, in fact, is exactly what happened next, according to a meeting summary uploaded nine days later. The dozens of pages of WIV dispatches that Reid unearthed, particularly those from November 2019, helped shape the conclusion of the interim report. Working out of a small, windowless room in the Hart building that they nicknamed “the Bat Cave,” the researchers cross-referenced Reid’s analysis with myriad clues, from procurement notices and patent filings to records of ongoing scientific experiments at the WIV. As their investigation grew, so did a timeline that unfolded across the walls like a giant checkerboard."......."Without the cooperation of China’s government, we can’t know exactly what did or didn’t happen at the WIV, or what precise set of circumstances unleashed SARS-CoV-2. But the dispatches that Reid unearthed, when overlaid with additional evidence the Senate team compiled, point to a catastrophe in the making: political pressure to excel, inadequate resources to safeguard risky work and an effort to skirt blame once a crisis hit. As Reid sees it, the international community must continue to demand answers. “If you just throw your hands in the air and say, ‘We’ll never know because it’s China,’ and just move on — if you take that defeatist approach to things — you can’t prepare yourself to prevent something like this from happening in the future.” (Eban K. 2022)

It goes on for pages to chronicle the reality of what happened in China that makes the case for a possible lab leak. So fascinating.

3) "Although microbial populations in the gut microbiome are associated with COVID-19 severity, a causal impact on patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. We first demonstrate SARS-CoV-2 infection induces gut microbiome dysbiosis in mice, which correlated with alterations to Paneth cells and goblet cells, and markers of barrier permeability. Samples collected from 96 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, including blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species. Analysis of blood culture results testing for secondary microbial bloodstream infections with paired microbiome data indicates that bacteria may translocate from the gut into the systemic circulation of COVID-19 patients. These results are consistent with a direct role for gut microbiome dysbiosis in enabling dangerous secondary infections during COVID-19."(Bernard-Raichon et. al. 2022)

Why does this matter? It is well known that human lifestyle decisions regarding food, chemical exposure, exercise volume, stress and much more dictate the health of the intestinal microbiome. The fact that individuals with poor Covid outcomes have dysbiosis (poor intestinal microbe diversity) is well known. These issues are now shedding further light on the fact that these bacteria are leaking into the blood stream triggering immune and inflammatory reactions that significantly worsen disease as we had seen in multi inflammatory syndrome in children.

The take home remains the same: spend time caring for your intestinal bacteria and they will care for you.

4) A good article in the Atlantic Magazine about the validity of hand washing as a mitigation measure against respiratory viral illnesses. The take home is as expected and as we noted play out in the Covid pandemic. 20 second soapy hand washing is useful to prevent most infectious transmission except for viral respiratory viral disease. Masks and avoidance are the only really useful mitigation measures here. (Stern J. 2022)


Non Covid Quick Hits:

5) "Low skeletal muscle mass is associated with cognitive impairment and dementia in older adults. This review describes the possible underlying pathophysiological mechanisms: systemic inflammation, insulin metabolism, protein metabolism, and mitochondrial function. We hypothesize that the central tenet in this pathophysiology is the dysfunctional myokine secretion consequent to minimal physical activity. Myokines, such as fibronectin type III domain containing 5/irisin and cathepsin B, are released by physically active muscle and cross the blood–brain barrier. These myokines upregulate local neurotrophin expression such as brain-derived neurotrophic factor (BDNF) in the brain microenvironment. BDNF exerts anti-inflammatory effects that may be responsible for neuroprotection. Altered myokine secretion due to physical inactivity exacerbates inflammation and impairs muscle glucose metabolism, potentially affecting the transport of insulin across the blood–brain barrier. Our working model also suggests other underlying mechanisms. A negative systemic protein balance, commonly observed in older adults, contributes to low skeletal muscle mass and may also reflect deficient protein metabolism in brain tissues. As a result of age-related loss in skeletal muscle mass, decrease in the abundance of mitochondria and detriments in their function lead to a decrease in tissue oxidative capacity. Dysfunctional mitochondria in skeletal muscle and brain result in the excessive production of reactive oxygen species, which drives tissue oxidative stress and further perpetuates the dysfunction in mitochondria. Both oxidative stress and accumulation of mitochondrial DNA mutations due to aging drive cellular senescence. A targeted approach in the pathophysiology of low muscle mass and cognition could be to restore myokine balance by physical activity." (Oudbier S. 2022)

This research is critical to our long term health. Activity is so important on so many levels, but in this case we are able to generate more BDNF and other enhanced metabolic properties of life for reduced inflammation and increased longevity in a healthful state. Everything is tied together in our neuroimmunometabolic pathways. To be sedentary, poorly nourished and toxic is to die younger with less functional ability of every system in the body. The take home point here is to get your children moving often and with vigor. That has a long term feed forward effect on keeping the brain clean and energetic in positive ways. Couple this data to the sleep data on glymphatics and sleep induced cleaning and you see a variable picture of preserving brain health. See above for a diagram of this reality.

We are going to dive deeper here next week.

6) New research from MIT notes that the Earth has corrected its atmosphere multiple times over its existence. Through a process called Silicate weathering whereby the silicate rock traps carbon dioxide reducing the overall atmospheres CO2. This is the current scientific explanation for how the Earth has been suitable for mammalian life for so long. From the article, "The global carbon cycle exerts substantial control over Earth’s climate through its influence on the atmospheric CO2 concentration. CO2 enters the ocean-atmosphere system due to solid Earth degassing and organic carbon oxidation, and is removed through the chemical weathering of carbonate and silicate rocks and subsequent carbonate burial in ocean sediments, as well as organic carbon burial. Weathering rates increase with temperature and CO2 concentration: This is hypothesized to lead to a long-term stabilizing feedback in which increases in surface temperatures are countered by drawdown of CO2, and vice versa. This feedback can help explain the puzzle of Earth’s enduring habitability even as stellar luminosity has changed significantly. It also justifies the useful “steady-state” assumption in the study of past carbon cycle change and is an important foundation for the “habitable zone” concept used in exoplanet research." (Arnscheidt et. al. 2022)

I bring this up only in the context of human behavior and how it affects our environment. We do not treat our planet well as witnessed by plastic pollution in the ocean, air pollution in major cities and industrial regions, Mississippi river delta fertilizer damage and on and on. The Covid lockdown proved one thing very quickly. When humans stop acting, mother nature takes back over as witnessed by animals returning to all habitats that they are pushed out of, water and air becoming significantly cleaner. I think that the same will occur with global warming. Regardless of if we change to prevent it from worsening at our hand in the short term, the Earth is primed to fix it over 100000 years as it has dealing dealing with volcanic eruptions and other massive carbon releases that could have made the planet unlivable. The Earth doesn't think in our small term of years.

Like the human body, all systems in general are geared for survival and creation. It is our individual and collective behaviors that stymie this reality.

That's all this week,

Dr. M


Park Time Magazine
Eban ProPublica
Bernard-Raichon Nature
Stern Atlantic
Oudbier Gerontology
Arnscheidt Science Advances
CDC Variants Page
CDC Covid Deaths