Volume 12, Letter 47 Coronavirus Update 74 plus other stuff

Omicron US strains: as of November 5th data - variants make up: BA.4.6 is 10%, BA.2.75 is 2%, BF.7 is 9%, BA.5 is 39%, BQ.1 is 17%, BQ1.1 is 19%

BA.5 has lost most of the ground it had held for a while to many new Omicron variant offshoots. BF.7, BQ.1 and BQ1.1 are very interesting as they are more infectious than BA.5. That remains amazing.

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)

Why are we seeing massive waves of RSV and Influenza A right now? These viruses normally circulate in the winter only. The answer is nuanced, but likely primarily because of the pandemics social distancing and hygiene activity. During the 2020-2022 cycle of Covid fear and mitigation of viral risk, most of us avoided the normal trappings of viral spread. We masked avoiding the viral droplet portal of entry most commonly used. We kept our children semi isolated from other children where most year to year viral transmission events occur. We practiced enhanced hand washing and sanitizing reducing natural viral spread through contact. In essence we stopped the normal propagation of respiratory virus for 2 years. A whole cycle of children between 0 and 2 years old are RSV and flu immune naive leading to a perfect host pool for spread. The 2 to 18 year olds have had a long pause in exposure reducing circulating virus specific antibodies to negligible levels leading to stronger infections and more spread. Anyone who has a child in college (me) has seen infection after infection pound these students this fall. It seems like they are always dealing with a viral illness. Immunity country wide will return in the coming year to these viral illnesses reverting to the old reality of winter predominance.

Quick Hits and other musings -

1) I spoke to Dr. Paul Offit this week after seeing the new data and he was right after all according to two new studies in BioRxIV. Dr. David Ho and his group looked at a small group of vaccinees from the old booster versus the new Omicron based bivalent booster and found that the new version offered no benefit over the ancestral strain based vaccine for the development of antibodies that are specific to omicron or more volume post vaccination. Dr. Dan Barouch and his group also found similar results noting that the immune imprinting reality has come to pass as Dr. Offit rightly predicted. The antibody response was similar between groups and there was no clinically relevant disease protection from the new bivalent boosters over the original strains, however, there needs to be more time to prove out this truth regarding clinical outcomes. That is the first impression. The antibodies produced are mostly against the ancestral strain and not the new omicron variant fulfilling Dr. Offit's immune imprinting discussion. If we go back to the Science Reynolds paper we also see similar issues playing out with natural and hybrid immunity realities. Go back and listen to podcast #27 to learn more about this topic from Dr. Offit.

Thus, it appears now for all intents and purposes that those individuals that had natural Wuhan, Alpha or Delta infections or were vaccinated with the ancestral mRNA vaccines and then get either omicron infection or a booster to omicron via the bivalent mRNA boosters, they will not mount a response against omicron specific antigens in a meaningful way, but will still maintain good protection against severe disease and hospitalization.

So, it appears that we will be getting repeatedly infected with the Omicron variants despite vaccinations and or prior infections with omicron. This is playing out very much like the reality of the common cold coronaviruses. Repeated illnesses and every year or two or three.

Going back to August 29th Covid Update we see:

In the interview with Dr. Offit there were a few big take aways:

·     Boosters for non risk based teen and young adults are unlikely to provide benefit while offering a small but real level of risk from myocarditis

·     Boosters are offering minimal benefit to the nation from a transmission perspective. At best 8-12 weeks of protection against symptomatic disease

·     Dr. Offit voted against adding omicron antigens to this fall's booster as there was limited data that it would any benefit. He was in the minority at the FDA advisory meeting, thus this fall's booster will have new strain genetics in it

·     The boosters could, not shown yet in humans, block future variant immunity to newer strains through viral immune imprinting

·     Humans need to pay more attention to their health to mitigate disease over time

·     We, as a society, need to stop tiptoeing around the concepts of lifestyle induced disease risk and in a non judging manner educate everyone in the risk categories, i.e

·     He clearly stated that we have achieved our goal with vaccinations, the reduction of death and hospitalization and it appears the 2 dose primary series was enough to achieve it

·     High risk groups are the ones that should vaccinate every time a new one is available based on the guidelines

In a recent piece in Time Magazine, Dr. Offit also offered the following: "That has vaccine experts divided. Dr. Paul Offit, a member of the advisory committee, says this strategy makes him “uncomfortable” for several reasons. He notes that the data presented from Pfizer-BioNTech and Moderna in June involving their BA.1 booster shot, which focused on the levels of virus-fighting antibodies the vaccine generated, were underwhelming. “They showed that the neutralizing antibody titers were between 1.5- and two-fold greater against Omicron than levels induced by a booster of the ancestral vaccine,” he says. “I’d like to see clear evidence of dramatic increase in neutralizing antibodies, more dramatic than what we saw against BA.1, before launching a new product. We’re owed at least that.” While conducting human studies does take more time, Offit says even a small trial involving about 100 people to measure their antibody levels after getting a BA.4/5 booster would be helpful. “You can boost people and measure their neutralizing antibodies two weeks later,” he says. Such information could also be critical in setting realistic expectations for the Omicron booster. The public might feel it’s a panacea that signals the end of the pandemic, but without any data showing how well the booster will protect people from not only getting sick, there might be unrealistic expectations about what the boost can do. “I get a little nervous, frankly, when I hear this [booster] is going to be miraculous,” Offit says." (Park A. 2022)

2) "Between Dec 8, 2020, and Feb 28, 2022, 16,208,600 individuals completed their primary vaccine schedule and 13,836,390 individuals received a booster dose. Between Dec 20, 2021, and Feb 28, 2022, 59,510 (0·4%) of the primary vaccine group and 26,100 (0·2%) of those who received their booster had severe COVID-19 outcomes. The risk of severe COVID-19 outcomes reduced after receiving the booster. Older adults (≥80 years vs 18–49 years), those with comorbidities (≥5 comorbidities vs none), being male (male vs female), and those with certain underlying health conditions—in particular, individuals receiving immunosuppressants (yes vs no)—and those with chronic kidney disease remained at high risk despite the initial booster. Individuals with a history of COVID-19 infection were at reduced risk (infected ≥9 months before booster dose vs no previous infection. Older people, those with multimorbidity, and those with specific underlying health conditions remain at increased risk of COVID-19 hospitalisation and death after the initial vaccine booster and should, therefore, be prioritised for additional boosters, including novel optimised versions, and the increasing array of COVID-19 therapeutics." (Agrawal et. al. 2022)

3) "In a sample of twice-vaccinated, older, community-dwelling US adults, self-reported systemic symptoms after SARS-CoV-2 mRNA vaccination were associated with greater antibody response vs local-only or no symptoms. These results agree with a previous report in US health care workers that showed higher postvaccination antibody measurements among those with significant symptoms after an mRNA vaccine. This report identifies age, sex, and Moderna vaccine as factors associated with both vaccine reactogenicity and immunogenicity, consistent with prior observations. No association was observed between symptoms after vaccination and race or ethnicity, body mass index, or comorbidities....Nonetheless, systemic symptoms remained associated with greater antibody response in multivariable-adjusted models, highlighting unexplained interpersonal variability....In conclusion, these findings support reframing postvaccination symptoms as signals of vaccine effectiveness and reinforce guidelines for vaccine boosters in older adults."(Hermann et. al. 2022) This is straightforward and relatively expected data. The more of an immune response to a virus or a vaccine is usually associated with a more robust antibody response. The problem again remains that this is only useful for 2-5 months as antibodies wane rapidly. Thus, as stated repeated boosting is important for the older and at risk population.

4) I find this piece in the Wall Street Journal enlightening when it comes to money spend that is misguided. From the article: "Since Covid shots first became available, the federal government has purchased and distributed them instead of relying on the market to match supply with demand. The result has been colossal waste. Between December 2020 and mid-May 2022, the U.S. wasted 82.1 million doses. Some expired on pharmacy shelves before they could be used; others were discarded after remaining unclaimed in opened multidose vials. The FDA authorized bivalent vaccines at the end of August for people who had received their primary dose series or their most recent booster shot at least two months prior. The CDC’s Advisory Committee on Immunization Practices ratified the recommendation, despite concerns among some members that the vaccines didn’t have enough testing on human subjects and that two months wasn’t long enough between shots. The Biden adm inistration announced on Sept. 8 that it had secured 170 million of the updated doses. It is still seeking an additional $22 billion from Congress to buy more." (Zinberg J. 2022)

The bivalent vaccine uptake in our office and nationally has been paltry at best and is likely to remain that way. Since the federal government bankrolled the entire project of Operation Warpspeed, there was little to no reason to over buy and waste federal dollars that could be spent to buy good food for people which could have a profound impact on health nationally. Money waste at the government level is constant. I digress.

5) Monika Gandhi has more great information to share: "Antibody-producing memory B-cells — generated by the vaccines or as a result of a prior infection — have been shown to recognize the virus, including the ability to adapt to the variant to which they are exposed. Although we do not know how long these memory B cells last, survivors of the 1918 influenza pandemic were able to produce antibodies from memory B cells when their blood was exposed to the same strain nine decades later.

The vaccines also trigger the production of T cells. While B cells serve as memory banks to produce antibodies when needed, T cells amplify the body's response to a virus and help recruit cells to attack the pathogen directly. T cells from the vaccine preserve polyfunctionality across the Omicron variant. Memory T cells generated by COVID-19 may last a lifetime, according to a study that examined participants with varying degrees of initial disease severity. Memory T cells generated in individuals who survived a different coronavirus infection in 2003 were shown in a recent paper to last at least 17 years.

Booster shots will just raise antibodies temporarily, but their effectiveness wanes several months later. However, each booster (or exposure) diversifies and broadens T-cell responses to the virus and a booster shot will also expand the potency of B cells, making them better able to respond to Omicron.

During the Omicron variant surge this winter, we did see a greater chance of reinfection compared with previous variants, but not in severe disease across the general population with two-dose vaccines. Booster shots helped older patients achieve greater protection against severe infection, however, and are most critical for those over 65 years of age. Those with any immunocompromising condition should also get additional shots." (Gandhi M. 2022)

Non Covid Quick Hits:

6) "In this study, compared with Non Video Game Users, Video Game Users were found to exhibit better cognitive performance involving response inhibition and working memory as well as altered BOLD signal in key regions of the cortex responsible for visual, attention, and memory processing. The findings are consistent with videogaming improving cognitive abilities that involve response inhibition and working memory and altering their underlying cortical pathways." (Chaarani et. al. 2022)

What we see on occasion in studies of video gaming is an uptick in processing and working memory. These findings are not surprising in the context of what modern video gaming requires of the user to complete the tasks. The issue remains that for most VG users the time spent becomes the detrimental wave toward dysfunction. Sedentary activity for hours is unhealthy. Focusing your vision on a narrow close by field for hours is a pathway to myopia. Spending hours gaming takes away from other events that are important, i.e. studies, sport, music, exploratory craft and imaginative learning.

Take this data for what it is. Video games are useful for 1-2 hours a day MAX.

That's all this week,

Dr. M

Collier BioRxIV

Goodman CNN

Reynolds Science

Agrawal Lancet

Hermann JAMANetwork

Zinberg WSJ

Gandhi Medscape Blog

Chaarani JAMANetwork

CDC MMWR

CDC Variants Page

CDC Covid Deaths