May 9th, 2022

North Carolina like the rest of the country is still without much Covid related illness although case trend is upward.

Salisbury Pediatrics is Covid testing between a zero and 2% positive rate week by week still. Influenza A is prominent in our practice.

In NC, we are down to 5% of admitted patients needing a ventilator and 10% needing an ICU bed for Covid. Historically low numbers and almost all are unvaccinated.

The 7 day moving average of cases for the US in recent weeks is at 66,000.

The risk of death is 0.000033 once vaccinated with a two dose series or survived natural infection.

As it stands today, the United States has had 81.5 million known cases and almost 995,000 deaths. The case numbers will continue to underestimate true case volume by 3-4x as home kit positives are not being reported.

If you did not read 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.

As with the first newsletter on this topic, keep solace with the fact that there is a 99+% chance of survival for all of us regardless of vaccination. However,
mathematically, you now have a 99.9998% chance of survival once vaccinated and the vaccine safety for the mRNA vaccines continues to look good.

Questions and Answers:

Men - Do you run from or bury your feelings?

100 % say yes

Men - are you holding deep wounds that you have not grieved or released?

50 % say yes

 

Omicron now has even more cousin strains: newer variant BA.2 makes up 62% of current case volume based on different parts of the country while omicron BA 1.1 is at 1% and B 2.12.1 is 37%. 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.

BA.4 and BA.5 are making waves in South Africa with an R0 infectiousness in the range of measles. Yikes from an infectiousness perspective. The new reproductive rate is 1 infects 12 which infects 144 which infects 1,728 which infects 20,736. That is a very fast spread rate.

Little else to report here. (CDC Variants)

From Monika Gandhi's Newsletter: "1) Masks: The ruling that the federal transportation mask mandate in the US was not legal this past week triggered a major re-evaluation of the effectiveness of mask mandates versus masks. Mask mandates didn’t seem to work because people use a variety of masks and cloth masks don’t seem to reduce transmission. However, good masks certainly work for the individual to limit exposure to a respiratory pathogen (e.g. N95, KN95, FFP2, KF94, double mask) so media/scientific literature turning to effectiveness of one-way masking (with good masks!) for anyone who wants to mask moving forward

2) Vaccine effectiveness in those with immunocompromising conditions: The mRNA vaccines work so well that there is a lot of data emerging that a strong immune response is generated even in those on chemotherapy, immunomodulator agents for rheumatologic conditions, HIV, and a host of other immuncompromising conditions. These are powerful vaccines. This leads to the booster discussion and who needs the 4th shot and when – the European equivalent of the CDC has decided on those with immunocompromised or those 80 years and older; the US guidelines are more permissive down to the age of 50

3) COVID zero: What is happening in China (specifically Shanghai where human rights violations are taking place in the name of COVID zero) reveals that we cannot eliminate COVID due to 4 reasons: 1) 29 species of animals carry (we cannot kill all these animals); 2) Long incubation period; 3) Symptoms look like other pathogens; 4) Vaccines increasingly non-sterilizing. However, we can reduce severe disease to very low rates by vaccination, monoclonal antibodies like Evusheld for immunocompromised, and oral antiviral treatments (Paxlovid, molnupiravir) – all of which need global access." (This email address is being protected from spambots. You need JavaScript enabled to view it.)

 

Quick Hits and other musings -

1) New variants - The recently emerged SARS-CoV-2 Omicron sublineages BA.2.12.1, BA.2.13, BA.4 and BA.5 all contain L452 mutations and show potential higher transmissibility over BA.2. The new variants’ receptor binding and immune evasion capability require immediate investigation, especially on the role of L452 substitutions. Herein, coupled with structural comparisons, we show that BA.2 sublineages, including BA.2.12.1 and BA.2.13, exhibit increased ACE2-binding affinities compared to BA.1; while BA.4/BA.5 displays the weakest receptor-binding activity due to F486V and R493Q reversion. Importantly, compared to BA.2, BA.2.12.1 and BA.4/BA.5 exhibit stronger neutralization evasion against the plasma of 3-dose vaccinees and, most strikingly, of vaccinated BA.1 convalescents....Together, our results indicate that Omicron can evolve mutations to specifically evade humoral immunity elicited by BA.1 infection. The continuous evolution of Omicron poses great challenges to SARS-CoV-2 herd immunity and suggests that BA.1-derived vaccine boosters may not be ideal for achieving broad-spectrum protection. (Cao et. al. 2022)

This is a very interesting study leaving us yet again realizing that the speed of Sars2 mutation is outpacing our ability to catch up to it and get close to any form of herd immunity. It appears very very unlikely that we will ever achieve herd immunity. The newer variant strains of Omicron lineage are more infectious by a large margin but remain no more deadly than BA.1 and less morbid than the delta strain based on current data.

Evasion of the antibody humoral system appears to be the new norm for this variant lineage based off of BA.1 leaving us in a quandary. Vaccines are minimally effective against stopping the spread of the illness at any level. Even omicron specific vaccines are not working to slow spread. The death risk is still decoupled from infection which remains great news. Therefore, we have to keep asking ourselves, what are we fighting for now? If we vaccinate the US with a strain specific BA.4/5 vaccine but the remainder of the world is unvaccinated, then the immune escape seen to date will make the new vaccine obsolete in short order. That is also assuming that a new variant doesn't emerge before the 100 day vaccine development period plus the days to distribute are completed. It is almost as if you need to have a perfect mass vaccination globally over 1 week to pull any sort of herd immunity off. Clearly, that will never happen. Thus, I ask again, what are we fighting for now? My answer - normal life. We have to learn to live with Covid and it's mutations over time. As always that leaves you in control of your lifestyle decisions that drive immune solvency and your safety when you get infected.

2) CDC seroprevelence study - As of February 2022, approximately 75% of children and adolescents had serologic evidence of previous infection with SARS-CoV-2, with approximately one third becoming newly seropositive since December 2021. The greatest increases in seroprevalence during September 2021–February 2022, occurred in the age groups with the lowest vaccination coverage; the proportion of the U.S. population fully vaccinated by April 2022 increased with age (5–11, 28%; 12–17, 59%; 18–49, 69%; 50–64, 80%; and ≥65 years, 90%). (CDC)

This data set confirms what we had suspected. The United States is now almost fully exposed to Sars2 in one variant or another and many also vaccinated. Therefore, the risk of death for most people has plummeted and should remain low for a long time based on T cell immune activity. There will continue to be emerging data that the vaccines will help reduce severity for high risk individuals against most if not all future variants. This is NOT to say that vaccination with boosters will stop at all the spread of disease based on current infectiousness of the new variants coupled to the immune escape of the vaccines and prior Sars2 infection.

With the vaccines now, we are playing whack a mole. The logistical reality of controlling the endemicity of Sars2 covid in the future remains daunting at best and on par with our ability to halt influenza yearly. (this is not a comparison of infectiousness as Sars2 is far more contagious than the flu)

We are truly in a new paradigm. The elderly and the immunocompromised individuals in the world are at high risk moving forward for a negative outcome. The new variants immune escape means that they will have a chance to set up shop rapidly in hosts before T cells come to play. This puts people on the back foot for immune resiliency and protection. I surmise that boosters for this population are the only true protection from death over time as Infections with Sars2 will be frequent and repeated.

3) More on boosters - Two studies from Israel looked at over 1 million doses of a fourth dose of Pfizer's mRNA vaccine in a greater than 50 year old population. The studies noted that protection against testing positive for SARS2 was 50% better with a fourth dose than those with only 3 doses and the protection had waned by 8 weeks. As seen in previous vaccine studies, protection against severe Covid was robust in this riskier population. (Bar-on et. al. 2022)(Magen et. al. 2022)

4) From a new study: COVID-19 survivors were less accurate and with slower response times than the matched control population – and these deficits were still detectable when the patients were following up six months later. The effects were strongest for those who required mechanical ventilation. By comparing the patients to 66,008 members of the general public, the researchers estimate that the magnitude of cognitive loss is similar on average to that sustained with 20 years ageing, between 50 and 70 years of age, and that this is equivalent to losing 10 IQ points. (Eurekaalert)

We know that in a subset of patients, covid crosses the blood brain barrier and induces inflammation. These individuals are at risk for brain degeneration or dysfunction over time. Age increases this risk likely due to microbiome, metabolic and immunologic changes induced by poor lifestyle behaviors. .

Again, like we discussed a few weeks ago. Aim to mitigate this risk by reducing inflammatory triggers including poor quality foods, toxins, sleep deprivation, stress and drug use.

5) From the British Medical Journal: The mRNA-1273 and BNT162b2 vaccines are effective in individuals who take immunosuppressants. However, individuals who are vaccinated but on immunosuppressants are still at higher risk of SARS-CoV-2 infection and COVID-19 hospitalisation than the broader vaccinated population. Booster doses are effective and crucially important for individuals on immunosuppressants. (Shen et. al. 2022)

6) Some individuals could have poor transport of omega 3 fats based on mutations in the gene Mfsd2a that encodes for a docosohexaenoic acid, DHA, transport protein. This defect can cause a decrease in the transport of DHA into the brain's cells leading to increased blood brain permeability which is an issue in Long Covid and post covid neurological sequelae. (Andreone et. al. 2017)(Ben-zvi et. al. 2014)

Another reason to increase your omega 3 fatty acid intake as fish oil or whole small cold water fish. That's all this week,

 Dr. M

 

Cao BioRxIV
Bar-On NEJM
Magen NEJM
EurekaAlert
Shen BMJ
Andreone Neuron
Ben-Zvi Nature
CDC MMWR
CDC Variants Page