April 25th, 2022

Omicron now has three strains: newer variant BA.2 makes up 74% of current case volume based on different parts of the country while omicron BA 1.1 is at 6 +% and B 2.12.1 is 19%. Delta and BA 1.1.529 are now gone by competition. Cases are increasing in some cities with little increase in hospital morbidity and mortality. In essence we are still fairing quite well in the new norm.

Little else to report here. (CDC Variants)

I flew this week for the first time without a mask. It was a real feeling of normalcy.

It was a feeling that we are finally waking up to the reality that Covid and many other illnesses are here to stay. Thus, we need to live that way. I say this for myself and all of the individuals that are lower risk and not risk averse. For everyone that chooses to keep their masks on, no problem. We are here to support your choice. We are a country that believes in choice above most things. Now that it is legal to do so, I will choose my path without a mask unless at work. No judgement. Don't listen to any media that judges or prejudges to know anything regarding this disease or pandemic. Follow the science and unbiased scientists looking out for your best interests. Don't trust anyone that cannot change their mind when presented with new data.

 Quick Hits and other musings -

1) A fascinating study published this month looked at the pathophysiology of PASC or long Covid issues. The authors include Inigo San Milan who is an expert in exercise physiology. The results are very important for our understanding of the fatigue and general dysfunction in post acute Sars2 Covid19 disease state. What did they find?

As they write in scientific terms: There is an urgent need to understand the pathogenesis of PASC and find effective treatments. The cardiopulmonary exercise test (CPET) is commonly used to investigate unexplained exertional dyspnea; as such, it could provide insight into mechanisms of PASC. CPET data can be used to calculate rates of β-oxidation of fatty acids (FATox) and of lactate clearance, providing insight into mitochondrial function. Fit individuals have better mitochondrial function and a higher rate of FATox during exercise than less fit individuals. Our results suggest that patients with PASC have significant impairment in fat β-oxidation and increased blood lactate accumulation during exercise, regardless of previous comorbidities. (de Boer et. al. 2022)

What the authors are saying in principle is that SASR2 causes a shift in the function of the energy centers of our cells and in this case specifically the muscle cell. The mitochondria are becoming the center of research of many disease states as they provide the energy for locomotion, thought, digestion and so much more.

Remember that we take all macronutrients in as food or beverage where they are broken down in the GI tract and then absorbed by the small intestine leading to small molecules of glucose, free fatty acids or amino acids being sent around the body for use as energy. The mitochondria in various cells in our body primarily use fat and glucose as the main energy players for most of us most of the time. For some reason, most likely a genetic predisposition, certain individuals are susceptible to a SARS2 induced shift in mitochondrial ability to burn fat as fatty acid oxidation and clear lactate after glycolysis of glucose. This shift leads to profound exercise intolerance and generalized fatigue. The mitochondria are prematurely shifting the substrate of energy generation from fat burning to glycolysis acting like an athlete at peak performance, i.e. zone 5 training versus what should be happening at lower levels of training which is fat oxidation. For more of the science from the article, see below.

2) "People are now confused about what it means to be fully vaccinated. It is easy to understand how this could happen. Arguably, the most disappointing error surrounding the use of Covid-19 vaccines was the labeling of mild illnesses or asymptomatic infections after vaccination as “breakthroughs.” As is true for all mucosal vaccines, the goal is to protect against serious illness — to keep people out of the hospital, intensive care unit, and morgue. The term “breakthrough,” which implies failure, created unrealistic expectations and led to the adoption of a zero-tolerance strategy for this virus. If we are to move from pandemic to endemic, at some point we are going to have to accept that vaccination or natural infection or a combination of the two will not offer long-term protection against mild illness." (Offit P. 2022)

This whole article is worth a read for an understanding on boosters in kids and adults - Link

3) From Drs. Gandhi and Noble - A Rational Roadmap to Future COVID Management:

"Sixth, we need a more targeted approach to boosters. This requires more precise reporting from the CDC, which involves categorizing severe breakthrough infections by the specific comorbidities and vaccination status of those hospitalized. Compared to many European countries such as the United Kingdom, the U.S. at large has failed to provide more detailed data on severe COVID-19 breakthroughs. More refined data will allow for more efficient targeting of further booster shots, prioritizing those most likely to benefit from regular boosting by age and health status." "we should continue to upgrade and improve our ventilation systems in public spaces, including schools, which will accrue long-term benefits from the reduced transmission of all respiratory pathogens to improved air quality in areas plagued by wildfires or other environmental pollutants."

These are 2 of the 10 items that I completely agree with. Not to mention that upgrading ventilation in schools has the added benefit of improving learning by reducing CO2 levels in the school learning space.

The article is worth reading in its entirety and can be found at this link.

4) "During this pandemic, we have all lost facial expression. It has been 2 years of the entire world having a masked facies. Has this lack of exposure to facial expression contributed to the sense of isolation that many of us feel? Has it deprived us of shared emotions, of empathy or led to misinterpreted feelings? On the other hand, perhaps we have also gained a new type of intimacy and deliberateness in our interactions, which get us beyond the immediate biases of seeing someone’s whole face. I find I spend more time really learning about who the person is. I truly savor moments of shared laughter. It will take time for us to recalibrate to the richness of full facial expression. As we begin to reveal ourselves to others once again, I am trying to be thoughtful about the expressions I convey, about the privilege of smiling and revealing the full extent of that smile, and how this in turn, might make someone else smile." (Ferenczi E. 2022)

I was surprised by the faces that lay behind the masks that have recently been revealed. My imagination had sent me down some very different pathways. I love seeing the smiles of children again. The facial affect of parents during discussion are now available for me to gaze upon a gauge involvement. There are so many nuances to the face that we have been missing out on. Thankfully, these nuances are back to help shed light on emotions, feelings, and so much more.

5) Ivermectin not useful for Covid. Most of the peer reviewed scientific data has come to this conclusion. However, one interesting association has some possible merit. Could the efficacy of Ivermectin seen in other parts of the world be related to a parasite called Strongyloides stercoralis? Ivermectin is an excellent treatment for this nematode. In an immunocompromised state, this worm can cause disseminated disease. Could Covid patients develop severe immune dysfunction allowing this parasite to overwhelm the patient leading to death? Thus, could it be that those treated with Ivermectin in parts of the world where the nematode is prevalent in human GI tracts have reduced Covid disease outcome burdens based on the reduction of nematode induced disease? This is plausible. (Wilson P. 2022 Medscape)(Gandhi et. al. 2022)

What I take away from this hypothesis is this - Ivermectin may turn out to have some benefit in person's with a parasitic burden preCovid exposure. It does not appear to have any effect otherwise. My real problem with the whole ivermectin story is that it was demonized and called horse medicine, voodoo, etc.... Before we truly knew the validity of it's action in the pandemic, we had to deal with a ridiculous media onslaught of negativity and shame around the thought of possibility. Medicine has to be very careful to not fall prey to indoctrinated beliefs based on non scientists or politically motivated scientists masquerading as the Knowers. The scientific method is very clear. Any hypothesis is valid until proven incorrect. We have a lot to learn still from the fallout of this pandemic. I lay a ton of blame at the feet of the political/medical/media complex that purports to be the knowers of truth before that is even possible. Faith in these institutions are at an all time low for me and many. It is now their responsibility to rebuild trust as it would be mine if and when I fail you.

6) Myopericarditis following Covid 19 vaccines versus other vaccines - The overall incidence of myopericarditis from 22 studies (405 272 721 vaccine doses) was 33·3 cases per million vaccine doses, and did not differ significantly between people who received COVID-19 vaccines. Compared with COVID-19 vaccination, the incidence of myopericarditis was significantly higher following smallpox vaccinations but was not significantly different after influenza vaccinations or in studies reporting on various other non-smallpox vaccinations. Among people who received COVID-19 vaccines, the incidence of myopericarditis was significantly higher in males (vs females), in people younger than 30 years (vs 30 years or older), after receiving an mRNA vaccine (vs non-mRNA vaccine), and after a second dose of vaccine (vs a first or third dose). (Ling et. al. 2022)

That's all this week,

Dr. M

De Boer ATS Journals
Offit NEJM
Ferenczi JAMA
Gandhi NEJMWatch
Ling Lancet Respiratory Medicine
CDC Variants Page

Our data suggest abnormally low FATox and altered lactate production by skeletal muscle as a putative cause of—or contributor to—the functional limitation of patients with PASC. Normally, as glycolysis increases with exercise intensity, lactate is oxidized for fuel in mitochondria, mainly in adjacent slow-twitch muscle fibers. Like FATox, lactate clearance capacity is a useful surrogate for mitochondrial function. In patients with PASC, even in those with normal pre–COVID-19 physical fitness and free of comorbidities, the metabolic disturbances of the skeletal muscle during exercise may be worse than those reported in moderately active individuals or in individuals with metabolic syndrome (3). Whereas rising blood lactate levels are expected during high exercise intensity (as glycolytic flux exceeds the rate of mitochondrial pyruvate oxidation), a high blood lactate at lower exercise levels indicates mitochondrial dysfunction (7). The inappropriately high arterial lactate levels at relatively low exercise intensity (e.g., >9 mM at 150 W) in patients with PASC indicate that the transition from FATox to CHOox occurs prematurely, suggesting metabolic reprogramming and dysfunctional mitochondria. Dysregulated lipid oxidation and decreased mitochondrial biogenesis have been reported in acute critically ill patients admitted to the ICU (8). However, the long-term weakness in ICU survivors is associated with heterogeneous muscle pathophysiology with variable combinations of muscle atrophy and impaired contractile capacity and not solely by diminished mitochondrial content (9). (de Boer et. al. 2022)