Omicron US strains: as of June 4th data - variants make up: BA.2 is 14%, BA.4 is 8%, BA.5 is 13%, and B 2.12.1 is 64%. This Covid wave is inline with volumes from wave three which was delta. Death and hospitalizations are not tracking with infectious volume at all anymore. We remain in a place of limited concern now that the morbidity is far below delta and earlier strains when everyone was SARS2 immune naive.
BA.4 and BA.5 are not showing any early signs of increased disease morbidity. This mirrors other countries battling these strains.
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.
Complete opinion: What is the current state of affairs? We have a highly contagious and mutational SARS2 virus that is present in the United States. The mutations usually occur overseas in vaccine naive areas. The landscape here has changed as most of us have some immunity as vaccine induced, viral induced or a hybrid combination. That reality has dramatically reduced the death and hospitalization rate so that my colleagues in the ICU feel little to no stress anymore from Covid despite relatively high case volume compared to other waves except wave 4. Thank God for this change as many are burned out or on their way there from 2 years of constant care. The current vaccines are not very useful for illness prevention as witnessed by the many people that I know that have had 4 doses of mRNA vaccines, the most recent being within 60 days, and still getting symptomatic illness requiring significant time to feel better. The data also supports the witnessed reality as boosters are offering less than 50% protection against symptomatic disease and waning antibodies within 60 days for most. The current vaccines and prior natural disease are very very reliable for preventing hospitalization and death as witnessed in the hospital data and T cells and memory B cells are fully functional in almost everyone. Risk stratification is the key to boosting moving forward as we have heard from thought leaders Paul Offit and Monica Gandhi in recent weeks.
There has been a very very poor national uptake of boosters with only a third of eligible adults getting one at 100 million. This is likely based on the poor effectiveness at preventing illness and the science showing that the primary series is protecting against death at a very high rate despite waning antibodies.
The Omicron variants are infecting within 3 days on average leaving little time for the T cells and B cells to respond fast enough to prevent symptomatic disease, but are fully protective for immunocompetent people against severe disease. The memory T and B cells are able to ramp up antibody and viral killing capacity fast enough to prevent lung and organ infiltration as was seen with earlier waves of disease when individuals had no immunity or vaccine exposure. This is great news as this prevents most if not all severe disease in immunologically solvent people. Immunologically, the antibodies need to be circulating in volume to prevent symptomatic disease. Thus, the only option for reasonable symptomatic disease prevention is vaccination every 2-5 months. Ugh. That sounds ridiculous and is. Thus it is not being recommended nor should it be.
We also now have paxlovid. A decent medicine antiviral that blocks a protease enzyme called mPRO which is a viral enzyme that plays an essential role in viral replication by cleaving the 2 viral polyproteins reducing replication slowing infections allowing the immune system to catch up and win. Link to diagram of drug action.
Put all together, we have a completely new situation that begs a major question that must be answered moving forward. Why are we pushing boosters for all adults between 12 years of age and 30 that are at best minimally effective for a few months in a population that is very very low risk at this point based on a priori vaccine and disease history. We have limited long term data on 4 and counting mRNA vaccines in teenagers and young children. I may not be towing the party line here, but I am finding it hard to want to boost my children who have been vaccinated and also had natural Omicron this year with no problem.
The big wild card remains a mutation in this variant set that becomes more deadly. All bets are off if this occurs. The good news is that based on history, we will have some warning as these events are and have occurred overseas to date. Will boosters mitigate that situation any more than natural infection? The current data sets say no as natural infection provides more wide ranging SARS2 epitope spread coverage and better antibody responses based on data reviewed in this newsletter.
My thoughts are these: 1) I am pro vaccine for all individuals that have not received a vaccine to date 2) we are in a much better place than we have ever been in this pandemic from a poor outcome perspective 3) we need a newer vaccine set that is targeted to the Omicron variants that actually reduces transmission significantly and lasts longer than a few months 4) We need a national narrative around immune solvency beginning with lifestyle decisions that are hurting immune function as discussed many times in this newsletter to help reduce infectious burdens and morbidity in general 5) We need to accept that people are very very skeptical about the booster and have good reason to be based on the data and illness while being boosted multiple times. More data needed to hone these opinions. And they are just that opinions.
Quick Hits and other musings -
1) From the United Kingdom, we have research published in Science noting: The Omicron, or Pango lineage B.1.1.529, variant of SARS-CoV-2 carries multiple spike mutations with high transmissibility and partial neutralizing antibody (nAb) escape. Vaccinated individuals show protection from severe disease, often attributed to primed cellular immunity. We investigated T and B cell immunity against B.1.1.529 in triple mRNA vaccinated healthcare workers (HCW) with different SARS-CoV-2 infection histories. B and T cell immunity against previous variants of concern was enhanced in triple vaccinated individuals, but magnitude of T and B cell responses against B.1.1.529 spike protein was reduced. Immune imprinting by infection with the earlier B.1.1.7 (Alpha) variant resulted in less durable binding antibody against B.1.1.529. Previously infection-naïve HCW who became infected during the B.1.1.529 wave showed enhanced immunity against earlier variants, but reduced nAb potency and T cell responses against B.1.1.529 itself. Previous Wuhan Hu-1 infection abrogated T cell recognition and any enhanced cross-reactive neutralizing immunity on infection with B.1.1.529.(Reynolds et. al. 2022)
This is a mess. In this study, if you were a healthcare worker and had been infected with an earlier SARS2 strain and were triple vaccinated with an mRNA vaccine and then you got ill with gen one omicron, your outcome from an immune perspective against future omicron variants was reduced. The reality that a person infected with the first Wuhan strain and then was triple vaccinated would end up with reduced and frankly impaired immunity against Omicron and future variants is very disturbing. This omicron variant has mutated in a way that has allowed it to mess with our immune system's response to it leaving us a little less prepared going forward. Little Trixter.
The immune system and this virus continues to marvel in good and bad ways. Section II has the entire discussion from this Science Journal article as it is very interesting.
2) A similar study was published in the Lancet Infectious Diseases this week noting from Sweden this time that individuals with triple vaccination status and previous SARS2 infection had weaker immune responses to Omicron compared to their vaccinated and not previously infected compatriots. (Blom et. al. 2022)
3) From a study in JAMA we find: The cohort included 7772 live births (7466 pregnancies, 96% singleton, 222 births to SARS-CoV-2 positive mothers), with mean (SD) maternal age of 32.9 (5.0) years; Preterm delivery was more likely among exposed mothers: 14.4% (32) vs 8.7% (654). Maternal SARS-CoV-2 positivity during pregnancy was associated with greater rate of neurodevelopmental diagnoses in unadjusted models as well as those adjusted for race, ethnicity, insurance status, offspring sex, maternal age, and preterm status. Third-trimester infection was associated with effects of larger magnitude. (Edlow et. al. 2022)
This data will need to be verified in future studies, however, it is concerning in that viruses often cause trouble during pregnancy and SARS2 should be no exception. The bottom line is for all of us to keep an eye on children born to SARS2 positive mothers for signs of delay. When identified, early childhood intervention with therapy is key.
4) mRNA vaccines (with Moderna being more associated) are showing myocarditis issues in teenagers and young men up to 39 years of age. This has to be part of the boosting calculus. More studies needed to show which causes more myocarditis now, boosters or natural disease post primary vaccine series or natural primary infection.
5) Novavax is finally getting a review by the FDA for emergency use which will be welcome news for those at risk for bad outcomes based on disease or age and refusing to take the mRNA vaccine or unwilling to get many boosters over time. Novavax vaccine is a direct injection of that spike protein itself, along with an adjuvant (a separate ingredient that excites the immune system to cause a response against the protein structure). This is the same type of vaccine style as our annual influenza vaccine. It is the only one currently in production in the US that is not a novel delivery method like the mRNA or Adenoviral vector types.
The vaccine's data shows that it is safe and effective. The only issue is a signal regarding myocarditis in young men and teenage boys that appeared to be greater than the mRNA issues noted over last 2 years. This issues will be looked at over the next months to a year. However, these risks are easily reduced by giving this vaccine to the at risk population which is mostly not the teenagers and young men.
6) My friends at the Pollution Detectives have been looking at indoor air quality and cognitive effects for years. No we see new interest in air quality related to infectious disease spread. From JAMA: Improving air quality has the potential to reduce not only infections with SARS-CoV-2 but also infections with other respiratory viruses and bacteria, reactive airway disease (eg, asthma) triggered by antigens, pulmonary and cardiovascular injury from inhalation of harmful respiratory particulates (eg, wildfires, smog), and toxicity from inhalation of volatile organic compounds. A once-in-decades opportunity now exists to make sustained improvements to public and private indoor air quality, reduce COVID-19 risk, and improve school, workplace, and consumer health and safety. Several methods are readily available to assess if improvements are working. Carbon dioxide monitors can provide insight on how well an occupied space is ventilated. Airflow measurement devices and tracer gas tests can directly examine ventilation rates. Aerosol sensors can determine the effectiveness of filtration systems. (Dowell et. al. 2022)
This is a great opportunity to repurpose wasteful governmental spending to a place of action and effect for the health of our children.
7) Vaccine for young kids - Pfizer's 2 dose series is 28% effective in preventing symptomatic disease in children aged 6 months to 5 years versus 37% for Moderna. (NYT coronavirus Briefing 6/15/22In a word, not effective to prevent illness. The kicker is for those at risk for a very rare but very bad outcome, it works great. The hard part is this, we have no idea who these exceedingly rare kids are. According to the CDC, 442 children have perished to date from Covid between the ages of 0 and 4 years. But, were those direct Covid deaths or associations. That I cannot answer. Overall, it is a small number, unless it is your child. Unfortunately, they do not risk stratify to know if there is a group that absolutely should be vaccinated. Most children that are older have natural immunity based on the statistics from the waves to date. Influenza by comparison kills less than 100 young children ( less than 5 years old) annually making covid more deadly overall. Thus, parents will have to weigh this data very carefully when deciding what to do. The AAP and CDC absolutely recommend the vaccines for all children over 6 months of age.
8) A very interesting study: report findings of 128 prospectively studied SARS-CoV-2 positive patients. Cognition and olfaction were assessed at 2-, 4- and 12-months post-diagnosis. Lung function, physical and mental health were assessed at 2-month post diagnosis. Blood cytokines, neuro-biomarkers, and kynurenine pathway (KP) metabolites were measured at 2-, 4-, 8- and 12-months. Mild to moderate cognitive impairment (demographically corrected) was present in 16%, 23%, and 26%, at 2-, 4- and 12-months post diagnosis, respectively. Overall cognitive performance mildly, but significantly declined. Cognitive impairment was more common in those with anosmia, but only at 2 months. KP metabolites quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine were significantly associated with cognitive decline. The KP as a unique biomarker offers a potential therapeutic target for COVID-19-related cognitive impairment. (Cysique et. al. 2022)
This is interesting from the perspective that having biochemical pathways identified as players in dysfunction can lead to interventions to resolve brain fog and cognitive decline.
9) Myocarditis is roughly 2 per 100000 person days according to a new analysis in the Lancet. (Wong et. al. 2022) It is most common after dose 2 of an mRNA vaccine in young men aged 18 to 25. Other studies to date have shown that myocarditis was more common following natural infection. This leads me to believe that the SARS2 spike protein is the causative trigger and a problem for all young men. Risk leans towards getting a vaccine series if unvaccinated and never infected. Boosters remain an unknown for risk when comparing other previously infected or vaccinated states.
10) Ivermectin safe but minimally useful says a study from Duke researcher Susanna Naggie. (Naggie et. al. 2022)
That's all this week,
Dr. M
