July 18th, 2022

 variants make up: BA.2 is 1%, BA.4 is 16%, BA.5 is 65%, and B2.12.1 is 17%. This Covid wave is inline with volumes from wave three which was delta. BA.5 is taking over as the new strain with excellent immune evading and vaccine evading skills. Every other strain is fading fast.

All strains are showing no signs of increased disease morbidity. North Carolina data is very clear here as we have transitioned to BA.5 we are not seeing any uptick in hospitalization and death. In NC, we are ticking down to 4% of admitted patients needing a ventilator and 11% needing an ICU bed for Covid.

R0 infectiousness is in the range 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.

Little else to report here. (CDC Variants)

Thoughts: As I was walking on the beach with my wife this week, I was marveling at the fact that there is still enough information worthy of writing about regarding SARS2 every other week. I would never have believed this 1 or 2 years ago.

The government is now pressing for Omicron strain specific vaccines for the fall which makes sense if we want to slow transmission as the current generation one boosters are not very useful in that regard. Novavax is going to be in this space as well for those that are uninterested in the mRNA vaccine type. See my later point, #2, about vaccinating the immune compromised globally if we want to slow the mutational spread which is the only way to stop the ever present need for more vaccine changes.

I find it interesting that the powers that be on the national stage are again promoting doom and gloom with BA.5 despite no signs of increased morbidity which is the true metric of problem. Increased infectiousness is certainly annoying and a true reality, but, fear of this strain appears misplaced now. The new reality for the world needs to be working hard on reducing future mutations which appears to be highly associated with immune compromised status in humans. Mask mandates are being looked at again in places like Los Angeles. When will it end? Who knows!

I am still struggling with the National guidance for mass boosting for the healthy and the younger aged. Scientifically, it makes little to no sense in the context of the function of the current mRNA vaccines. The uptake of the boosters in these groups is a referendum on the guidance as very few people find it a good choice. 198 million Americans over 18 years of age received the 2 dose primary series. 101 million received the first booster and only 17 million received the next or more boosters. That response is vastly different than political or some other ideology. It is the truth that they don't work well and for any reasonable length of time.

I find it a brilliant idea to vaccinate those individuals with immune issues globally every 3-6 months based on the latest data. This sounds like a viable strategy for some mutational control.

If anyone is interested in sharing, I would love to hear and share your thoughts regarding how this newsletter and even the podcasts have helped you navigate the covid experience these past years. All comments are welcome.

Quick Hits and other musings -

1) From a study by the Veterans Affairs Administration we have this report: First infection with SARS-CoV-2 is associated with increased risk of acute and post-acute death and sequelae in the pulmonary and extrapulmonary organ systems. However, whether reinfection adds to the risk incurred after the first infection is not clear. Here we use the national health care databases of the US Department of Veterans Affairs to build a cohort of people with first infection (n = 257,427), reinfection (2 or more infections, n = 38,926), and a non-infected control group (n = 5,396,855) to estimate risks and 6- month burdens of all-cause mortality, hospitalization, and a set of pre-specified incident outcomes. We show that compared to people with first infection, reinfection contributes additional risks of all-cause mortality, hospitalization, and adverse health outcomes in the pulmonary and several extra-pulmonary organ systems (cardiovascular disorders, coagulation and hematologic disorders, diabetes, fatigue, gastrointestinal disorders, kidney disorders, mental health disorders, musculoskeletal disorders, and neurologic disorders); the risks were evident in those who were unvaccinated, had 1 shot, or 2 or more shots prior to the second infection; the risks were most pronounced in the acute phase, but persisted in the post-acute phase of reinfection, and most were still evident at 6 months after reinfection. Compared to non-infected controls, assessment of the cumulative risks of repeated infection showed that the risk and burden increased in a graded fashion according to the number of infections. The constellation of findings show that reinfection adds non-trivial risks of all-cause mortality, hospitalization, and adverse health outcomes in the acute and post-acute phase of the reinfection. Reducing overall burden of death and disease due to SARS-CoV-2 will require strategies for reinfection prevention.(Al-Aly et. al. 2022)

This is concerning data overall. However, this is a 90% male population with an unknown comorbidity situation. These patients are in the VA system making the comorbidity likelihood higher. That in turn would denote increased inflammatory risks which in turn causes increased tissue damage and increased disease concerns as stated. However, this begs the reality that we need high quality newly Omicron BA.4/5 targeted vaccines to stem this tide until a new variant plagues us. Oh the webs that we weave in the fight against this little trixter.

2) From a study in Nature Medicine the authors state: In some immunocompromised patients with chronic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, considerable adaptive evolution occurs. Some substitutions found in chronic infections are lineage-defining mutations in variants of concern (VOCs), which has led to the hypothesis that VOCs emerged from chronic infections. In this study, we searched for drivers of VOC-like emergence by consolidating sequencing results from a set of 27 chronic infections. Most substitutions in this set reflected lineage-defining VOC mutations; however, a subset of mutations associated with successful global transmission was absent from chronic infections. We further tested the ability to associate antibody evasion mutations with patient-specific and virus-specific features and found that viral rebound is strongly correlated with the emergence of antibody evasion. We found evidence for dynamic polymorphic viral populations in most patients, suggesting that a compromised immune system selects for antibody evasion in particular niches in a patient’s body. We suggest that a tradeoff exists between antibody evasion and transmissibility and that extensive monitoring of chronic infections is necessary to further understanding of VOC emergence. (Harari et. al. 2022)

When we have global flairs of Covid 19, there is clear evidence now that individuals that are immune compromised have become breeding grounds for genomic mutations in SARS2 leading to variants of concern. The virus, in individuals with impaired immune ability, has the ability to slowly replicate over time adding more and more mutations that eventually lead to better transmission and spread. This occurs because the immune system does not effectively kill the virus in the normal 3 to 8 day time frame leading to months of replicative activity. These variants become our new circulating troublemakers.

Thus, in my opinion, we should be making vaccines in this country that are high quality and targeted to the current circulating strain. Then we should be releasing it worldwide very quickly to people in immune compromised states first. This should have the effect of slowing down these emerging VOC's that are evading our natural and vaccine induced immunity due to immune dysfunctions.

We will be stuck in a whack a mole variant world for a long time until we can get the immunecompromised reservoirs protected from infection globally. And this may be impossible.

3) Some gene SNP's or single nucleotide polymorphisms are associated with worse outcome from covid. This part continued from last week looks at the reality that we all have SNP's of varying degrees in our genome and that they are only of interest when we get severely sick or inflamed during an illness. The tissue damage during the illness exposes our own tissue and immune system to to each other leading to over reactions that we see of as autoimmunity and cancer over time. (Grolmusz et. al. 2022) It is highly concerning that Covid19 will be the genesis of a whole new wave of these types of diseases in individuals with comorbid disease, SNP's and time. The soup has been made for many and we will be waiting for these shoes to drop.

4) Vaccine boosters coming out this fall will contain viral segments from early strains as well as the newer BA.4 and BA.5. This should really help those that take it to resist the viruses ability to make us symptomatically sick for now. Current boosters offer little to no value to us that are not in a high risk pool and have had natural illness as I had in February. From a National Geographic article: "Additionally, not all experts agree that boosters are necessary once people pass the somewhat arbitrary threshold of age 50.“I just think this sort of blanket notion of everybody over 50 getting this vaccine doesn’t make sense,” says Paul Offit, a professor of pediatrics in the Division of Infectious Diseases at Children's Hospital of Philadelphia and one of two FDA advisory committee members who voted against including Omicron components in the fall boosters. It makes more sense for people over age 70 because their less vigorous immune systems aren’t as good at stopping a mild infection from progressing to a moderate or severe one, Offit said. But at age 71 himself, Offit has only gotten his first booster. He feels that the single extra shot, along with the fact that he had a recent natural COVID-19 infection, offers about as much protection as possible because antibody levels fall so quickly after getting additional boosters. Adults over 50 who have had an Omicron infection in the last six months already have more immunity from the infection than they’d get from another booster shot, based on data presented at the June 28 committee meeting." (Haelle T. 2022)

More high quality commentary to listen to.

5) In a recent study of US blood donations, the combined seroprevalence from infection or vaccination reached 94.7% by December 2021. (Jones et. al. 2022) We are creeping towards a place where every single person in this country has had Sars2 infection and or vaccination. Thus, we remain in a very enviable place with regards to death and hospitalization moving forward. Variants will come and go and cause us irritation due to increased transmissibility and immune escape from prior infections. However, there are zero signs that increased severity will show up.

I remain steadfast in the belief that lifestyle decisions that promote immune solvency are by far the best avenue to disease prevention and morbidity prevention moving forward. Vaccines are useful for high risk individuals but not at the expense of quality self care. A vaccine booster is no longer going to be the savior from bad outcomes if you remain inflamed and generally unhealthy in the new variant world as we will likely be playing variant whack a mole with vaccine production.

6) From Dr. Kerner's article we see: For example, the discovery that the pathogenesis of the disease in 20% of patients with critical COVID-19 pneumonia can be explained by either IEIs of type I IFN immunity or pre-existing autoantibodies neutralizing type I IFNs is an outstanding finding for common infections, for which monogenic lesions have never been shown to underlie more than 1% of cases for other conditions. Also, GWAS data suggest that the risk of hospitalization for COVID-19 is 60% higher in carriers of the Neanderthal haplotype, which is at least three times more frequent in individuals of South Asian descent (>50%) than in individuals with European ancestry (16%). This, together with unaccounted sociodemographic factors, may partly explain the higher risk of infection or hospitalization for COVID-19 in minorities of South Asian ancestry living in the UK. Two independent studies aiming to determine the cellular basis of the increase in the risk of severe disease associated with this locus have suggested that this outcome may result from a decrease in CXCR6 levels. (Kerner et. al. 2022)

This is truly the future of medicine where we have targeted data that gives us a window into risks of various pathogens moving forward based on genetic heritage and the immune makeup based on it. The future is so bright as technology opens our eyes.

7) Children lost significant volumes of movement time over the Pandemic. From JAMA Pediatrics: Twenty-two studies including 46 independent samples and 79 effect sizes from 14,216 participants (median age, 10.5 years; range, 3-18 years) were included. The percentage change in the duration of engagement in total daily physical activity from before to during COVID-19 was −20%. Moderation analyses revealed that changes were larger for higher-intensity activities, corresponding to a 17-minute reduction in children’s daily moderate-to-vigorous physical activity levels. The reduction in physical activity was also larger for samples located at higher latitudes and for studies with a longer duration between physical activity assessments. (Neville et. al. 2022)

This has multiple long term consequences to these children: metabolism dysregulation through hyperglycemia from lack of insulin independent glucose muscle uptake, immune dysregulation from sedentary and metabolic shifts in immune macrophage and innate cell polarity, lipid dysregulation and much more. Movement is critical for long and short term health.

8) The effectiveness of previous infection alone against symptomatic BA.2 infection was 46.1%. The effectiveness of vaccination with two doses of BNT162b2 and no previous infection was negligible, but nearly all persons had received their second dose more than 6 months earlier. The effectiveness of three doses of BNT162b2 and no previous infection was 52.2%. The effectiveness of previous infection and two doses of BNT162b2 was 55.1%, and the effectiveness of previous infection and three doses of BNT162b2 was 77.3%. Previous infection alone, BNT162b2 vaccination alone, and hybrid immunity all showed strong effectiveness (>70%) against severe, critical, or fatal Covid-19 due to BA.2 infection. Similar results were observed in analyses of effectiveness against BA.1 infection and of vaccination with mRNA-1273. (Altarawenh et. al. 2022)

These results are in line with most of the data related to previous variants as the protection against severe disease is great across all groups that were vaccinated, infected or a hybrid of both. The three dose benefit is misleading as the time to measure that 77% number was 45 days or less for the study participants. The waning value of the third booster is 2 months in general.

That's all this week,


Dr. M

Al-Aly Research Square
Harari Nature Medicine
Grolmusz Frontiers in Immunology
Haelle National Geographic
Jones JAMA
Kerner European J Human Genetics
Neville JAMAPediatrics
Sahly NEJM journal Watch
Altarawenh NEJM
CDC Variants Page
CDC Covid Deaths