February 28th, 2022

 

Omicron's sibling is the new variant BA.2. It appears to be very very similar to Omicron from the same lineage genetically with 50 amino acid changes. It is more infectious by 10-30% by most recent data. No data that it is more deadly to date in humans although a preprint article from a Japanese research group noted that in an animal model the disease is worse than BA.1 Omicron. (Yamasoba et. al. 2022) They noted more cellular fusion increasing infectivity and also more lung cell infection increasing morbidity. The immune protection from BA.1 against BA.2

was reduced by 6X. This does not mean that humans will respond the same way as the animal model results. It bears watching. So far, I have seen no data that humans are suffering worse disease. United States BA.2 numbers remain less than 10% likely due to the quality immunity achieved following the massive Omicron BA.1 surge the past 8 weeks. Our T and B cell immunity from BA.1 should serve to protect most of us from any issues with BA.2. Time will tell, but so far so good.

Yamasoba BioRxIV

Omicron Overview this week.

As I discussed last Covid update, the Omicron variant found me finally in a consciously un-boosted state. My residual Omicron side effects over the past 3 weeks were exercise induced fatigue and a very mild dry cough. Nothing else hit me this go round. This reality should play out the same for most people that have been vaccinated and or had natural disease coupled to a healthy lifestyle.

Quick Hits -

Children's mental health suffered significantly during the pandemic due to many different upstream negative changes including isolation, increased exposure to home stressors, poor nutritional access, anxiety due to disease fears, reduced exercise due to infection fear, and much more.

1) From the CDC this year, let's look at some of the Emergency Department data as a proxy for COVID related changes in children's health.

CDC examined changes in U.S. ED visit trends to assess the continued impact of the pandemic on visits among children and adolescents aged 0–17 years (pediatric ED visits). Compared with 2019, pediatric ED visits declined by 51% during 2020, 22% during 2021, and 23% during January 2022. I am going to reproduce the CDC data here with my take on it afterwards.

Among children aged 5–11 years, the number and proportion of cannabis-involved visits increased during 2020 and 2021 compared with 2019, with an increase of four visits per week during 2020 and an increase of nine visits per week during 2021. - This is likely a reflection of increased cannabis use nationwide coupled to lax parenting during the isolating pandemic.

The number and proportion of visits for psychosocial concerns also increased during 2021 and January 2022 compared with 2019, with an increase of 20 visits per week during 2021 and 35 visits per week during January 2022. This is a direct reflection of the heightened stress induced mood changes in children during the prolonged pandemic. These numbers are also reflected in our clinic as mental health visits have jumped significantly over the past 2 years.

During 2021, the number and proportion of visits for firearm injuries, self-harm, and drug-poisoning were higher compared with 2019, with an increase of two visits per week for firearm injuries, six visits per week for self-harm, and seven visits per week for drug poisoning. Self harm is the disturbing stat here as it is another marker of severe mental stress changes in young children.

Among adolescents aged 12–17 years, during 2020, 2021, and January 2022, the number and proportion of visits for injuries from physical activities (e.g., walking, swimming, and running) decreased compared with 2019, with decreases of 1,669 visits per week during 2020, 966 visits per week during 2021, and 757 visits per week during January 2022. Conversely, the number and proportion of visits for self-harm increased in all 3 years, with increases of 30 visits per week during 2020, 210 visits per week during 2021, and 207 visits per week during January 2022. This data set is disturbing in that teens are not active and are more stressed in their sedentary home based environments. When we see less physical activity overall in this age group, we will see significant negative downstream effects on glucose metabolism, gut health and mood. Movement is also critical for healthy sleep at this age. This age group needs to be active to succeed on many fronts.

Similarly, the number and proportion of visits for drug poisonings and eating disorders increased during all 3 years compared with 2019, with increases of 12 visits per week for drug poisonings during 2020, 171 visits per week during 2021, and 178 visits per week during January 2022; and increases of nine visits per week for eating disorders during 2020, 41 visits per week during 2021, and 38 visits per week during January 2022. The number and proportion of visits for firearm injuries increased by 22 visits per week during 2020 and by 20 visits per week during January 2022 compared with 2019. The number and proportion of visits for psychosocial concerns and for symptoms of mental health conditions and substance use increased during 2021 and January 2022, with increases of 78 visits per week during 2021 and 62 visits per week during January 2022 for psychosocial concerns and increases of 113 visits per week during 2021 and 197 visits per week during January 2022 for symptoms of mental conditions and substance use.

Weekly ED visits among adolescent females (aged 12–17 years) increased for eating and tic disorders during 2020 and depression, eating, tic, and obsessive-compulsive disorders during 2021. The proportion of ED visits with eating disorders doubled among adolescent females; those for tic disorders approximately tripled during the pandemic. (CDC)

Overall, this data set paints a picture that we knew was on the horizon based on school closures, lockdowns and other pandemic mitigation measures that had minimal to no effect on pandemic control, but a profoundly negative effect on many children and teens. It was a lose lose and still is.

2) As the volume of mental health issues rise in the nation, schools will be ground zero for access points to help struggling children. As many home situations are less than ideal adding to children's stressors, it will take a village to quell the damage and reverse course. Psychologists and teachers will be tasked with identifying the children at risk and providing intervention services as needed. These will be tricky times moving forward, but our collective vigilance will be profoundly useful for at risk children.

3) "The COVID-19 pandemic has introduced new challenges for governments and individuals. Unprecedented efforts at reducing virus transmission launched a novel arena for human face recognition in which faces are partially occluded with masks. Previous studies have shown that masks decrease accuracy of face identity and emotion recognition. The current study focuses on the impact of masks on the speed of processing of these and other important social dimensions. Here we provide a systematic assessment of the impact of COVID-19 masks on facial identity, emotion, gender, and age. Four experiments (N = 116) were conducted in which participants categorized faces on a predefined dimension (e.g., emotion). Both speed and accuracy were measured. The results revealed that masks hindered the perception of virtually all tested facial dimensions (i.e., emotion, gender, age, and identity), interfering with normal speed and accuracy of categorization. We also found that the unwarranted effects of masks were not due to holistic processes, because the Face Inversion Effect (FIE) was generally not larger with unmasked compared with masked faces. Moreover, we found that the impact of masks is not automatic and that under some contexts observers can control at least part of their detrimental effects." (Fitousi et. al. 2021)

For children at young ages, these mask related processing issues may compound over time delaying development. How this plays out over time is unknown. Only time will answer the ability to catch up to normal once the masks stay away. Humans are resilient, however, delays in development are delays. Thus, reaching maximal potential in any sphere may not occur now.

4) Another great fear that I have related to children's mental health at this time stems from the year plus of missed education and support for tens of thousands of North Carolina's inner city underprivileged children do to zoom nightmares or just lost to the system. These children will be missing a year and a half of critical foundational material from which to build upon for the future of their education.

From McKinsey Corp in July of 2021: "Our analysis shows that the impact of the pandemic on K–12 student learning was significant, leaving students on average five months behind in mathematics and four months behind in reading by the end of the school year. The pandemic widened preexisting opportunity and achievement gaps, hitting historically disadvantaged students hardest. In math, students in majority Black schools ended the year with six months of unfinished learning, students in low-income schools with seven. High schoolers have become more likely to drop out of school, and high school seniors, especially those from low-income families, are less likely to go on to postsecondary education. And the crisis had an impact on not just academics but also the broader health and well-being of students, with more than 35 percent of parents very or extremely concerned about their children’s mental health. The fallout from the pandemic threatens to depress this generation’s prospects and constrict their opportunities far into adulthood. The ripple effects may undermine their chances of attending college and ultimately finding a fulfilling job that enables them to support a family. Our analysis suggests that, unless steps are taken to address unfinished learning, today’s students may earn $49,000 to $61,000 less over their lifetime owing to the impact of the pandemic on their schooling. The impact on the US economy could amount to $128 billion to $188 billion every year as this cohort enters the workforce.""To assess student learning through the pandemic, we analyzed Curriculum Associates’ i-Ready in-school assessment results of more than 1.6 million elementary school students across more than 40 states. We compared students’ performance in the spring of 2021 with the performance of similar students prior to the pandemic. Students testing in 2021 were about ten points behind in math and nine points behind in reading, compared with matched students in previous years." (McKinsey and Company Report 7/21)

When you look at the actual report, you will see graphs that are very illustrative of the risk moving forward. These are daunting stats for us to overcome. This has to be ground zero for the state and federal governments action list post pandemic.

5) A second comprehensive look at the learning gap from McKinsey was released in 12/21: "Our analysis finds that students remain behind in both math and reading. What’s more, gains made since the spring are uneven. While some students are making up lost ground, others are stagnating. For example, students in majority-Black schools remain five months behind their historical levels in both mathematics and reading, while students in majority-White schools are now just two months behind their historical levels, widening prepandemic achievement gaps. This means that, in math, students in majority-Black schools are now 12 months behind their peers in majority-White schools, having started the pandemic nine months behind. Similarly, concerns around student mental health have lessened somewhat since the spring, but they remain higher than before the pandemic. Furthermore, we aren’t even out of the woods yet. Disruptions to learning are not over, and student attendance rates lag significantly behind prepan¬demic levels. While actual closures of whole schools or districts have affected just 9 percent of students, quarantines and other disruptions have affected 17 percent of in-person students. On top of school closures, absenteeism rates have risen, with 2.7 times as many students on a path to be chronically absent from school this year compared with before the pandemic. While absenteeism rates for high-income students are leveling off, rates for low-income students have continued to worsen since the spring, despite the return to in-person school. If historical correlations between chronic absenteeism and high school graduation hold, this could translate into an additional 1.7 million to 3.3 million eighth–12th graders dropping out of school because of the pandemic." (McKinsey and Company Report 12/21)

Again, the entire report is worth your time. Focus your attention on making sure that your child is closing the gaps that arose during the pandemic. It is never good to see racial and socioeconomic gaps widen as they will play out over time as lost wages, worsened health and mental stress. We must work tirelessly to close these gaps for all children.

Again, I repeat that as a rich nation, no child should ever go hungry, uneducated or wanting for the basics of existence. Stop spending money on any service over a child's health especially foreign aid, military, subsidized crops, lifetime healthcare for congress, etc... How do these needs trump the health of our future? I will never understand the politics of children's health.

6) Famotidine, a heartburn drug, is helpful for Covid infected patients according to a new study in Gut: "Rate of symptom resolution was improved for patients taking famotidine (p<0.0001). Estimated 50% reduction of overall baseline symptom scores were achieved at 8.2 days for famotidine and 11.4 days for placebo treated patients. Differences were independent of patient sex, race or ethnicity. Five self-limiting adverse events occurred (famotidine, n=2 (40%); placebo, n=3 (60%)). On day 7, fewer patients on famotidine had detectable interferon alpha plasma levels (p=0.04). Plasma immunoglobulin type G levels to SARS-CoV-2 nucleocapsid core protein were similar between both arms." (Brennan et. al. 2022)

This is a good analysis. We have long known that cimetidine is an immune modulator. Thus, finding out that famotidine is useful is expected and welcomed. Consider adding this drug to your cabinet for Covid if you have risk for a negative covid outcome.

7) A very good article on Long Covid is available with microscopic pictures at this link.

8) Immunity post natural infection lasts considerably longer than post 2 dose mRNA vaccination. Antibody related immunity last roughly 6 months post vaccine only. Natural infection plus a vaccine dose lasted well north of a year. (Hall et. al. 2022) Again, this is only antibody related. T cell activity lasts much longer and with better mutational specificity. The bottom line remains that in multiple studies now, natural infection once vaccinated or the other way around vastly trumps vaccine alone. Again, it is highly unlikely that repeated boosters makes any sense for the vast majority of us. Only, the high risk groups appear to need boosters 4 and on.

9) "The molecular mechanisms governing orderly shutdown and retraction of CD4+ type 1 helper T (TH1) cell responses remain poorly understood. Here we show that complement triggers contraction of TH1 responses by inducing intrinsic expression of the vitamin D (VitD) receptor and the VitD-activating enzyme CYP27B1, permitting T cells to both activate and respond to VitD. VitD then initiated the transition from pro-inflammatory interferon-γ+ TH1 cells to suppressive interleukin-10+ cells. This process was primed by dynamic changes in the epigenetic landscape of CD4+ T cells, generating super-enhancers and recruiting several transcription factors, notably c-JUN, STAT3 and BACH2, which together with VitD receptor shaped the transcriptional response to VitD. Accordingly, VitD did not induce interleukin-10 expression in cells with dysfunctional BACH2 or STAT3. Bronchoalveolar lavage fluid CD4+ T cells of patients with COVID-19 were TH1-skewed and showed de-repression of genes downregulated by VitD, from either lack of substrate (VitD deficiency) and/or abnormal regulation of this system." (Chauss et. al. 2021)

This is a complex but very important study. Vitamin D remains a very important nutrient for immune solvency. In this case, vitamin D helps to down regulate the TH1 killer activity post Covid that is driving excessive inflammation and damage. Genetic mutations and/or vitamin D insufficiency will drive excessive Th1 activity and inflammation leading to worse outcomes.

For more on Vitamin D as a therapy in general, read this newsletter.

10) "The SARS-CoV-2 Omicron variant has multiple Spike (S) protein mutations that contribute to escape from the neutralizing antibody responses, and reducing vaccine protection from infection. The extent to which other components of the adaptive response such as T cells may still target Omicron and contribute to protection from severe outcomes is unknown. We assessed the ability of T cells to react with Omicron spike in participants who were vaccinated with Ad26.CoV2.S or BNT162b2, and in unvaccinated convalescent COVID-19 patients (n = 70). We found that 70-80% of the CD4 and CD8 T cell response to spike was maintained across study groups. Moreover, the magnitude of Omicron cross-reactive T cells was similar to that of the Beta and Delta variants, despite Omicron harbouring considerably more mutations. Additionally, in Omicron-infected hospitalized patients (n = 19), there were comparable T cell responses to ancestral spike, nucleocapsid and membrane proteins to those found in patients hospitalized in previous waves dominated by the ancestral, Beta or Delta variants (n = 49). These results demonstrate that despite Omicron’s extensive mutations and reduced susceptibility to neutralizing antibodies, the majority of T cell response, induced by vaccination or natural infection, cross-recognises the variant. Well-preserved T cell immunity to Omicron is likely to contribute to protection from severe COVID-19, supporting early clinical observations from South Africa." (Keeton et. al. 2022)

More excellent data giving us true insight into protection long term against Omicron BA.1 and almost assuredly BA.2. The T cells are prepped and ready to attack, control and suppress Omicron preventing severe disease and death. Frankly, little else matters in this pandemic. As stated last Covid update, natural infection to Omicron, which most of us have now, is likely to provide durable protection against future variants for a long time. Antibody levels are likely meaningless moving forward. If they are high, great. If not, no problem. T cells are here to stay and protect.

11) Heart disease risk increases after Covid disease. In a massive Veterans Affairs study, Dr. Xie and colleagues noted that veterans who had recovered from SARS2/COVID-19 had dramatic increases in cardiovascular problems during the year post infection. Recovered COVID19 patients were over 50% more likely to have a cerebrovascular accident/stroke. Heart failure increased by more than 70%. Being hospitalized with COVID19 added another layer to the overall risk of many cardiovascular complications. The other noted complications included myocarditis, arrhythmia, thromboembolism/pulmonary embolism, myocardial infarction/heart attack and more. (Xie et. al. 2022)

It was well known early on in the pandemic that COVID was affecting the blood vessels and thrombotic pathways based on research out of Oak Ridge Labs in Tennessee. Thus, these findings are inline with expected outcomes. It remains critical from now on that all individuals that have genetic risk factors for these diseases get vaccinated and maintain an anti-inflammatory lifestyle. This disease is not going away according to current realities, therefore, self care is the only best option. If Covid eventually becomes a common cold, then great. If not, then prepare for your eventual infection.

12) As North Carolina's Data for ICU use and the use of ventilators can be found at: NCDHHS. The numbers remain much lower than Deltas peak despite massive case volume.

13) "SARS-CoV-2 Omicron is highly transmissible and has substantial resistance to antibody neutralization following immunization with ancestral spike-matched vaccines. It is unclear whether boosting with Omicron-specific vaccines would enhance immunity and protection. Here, nonhuman primates that received mRNA-1273 at weeks 0 and 4 were boosted at week 41 with mRNA-1273 or mRNA-Omicron. Neutralizing antibody titers against D614G were 4760 and 270 reciprocal ID50 at week 6 (peak) and week 41 (pre-boost), respectively, and 320 and 110 for Omicron. Two weeks after boost, titers against D614G and Omicron increased to 5360 and 2980, respectively, for mRNA-1273 and 2670 and 1930 for mRNA-Omicron. Following either boost, 70-80% of spike-specific B cells were cross-reactive against both WA1 and Omicron. Significant and equivalent control of virus replication in lower airways was observed following either boost. Therefore, an Omicron boost may not provide greater immunity or protection compared to a boost with the current mRNA-1273 vaccine." (Gagne et. al. 2022 )

This data set is frankly very surprising to me. I would have predicted the opposite. Such is the world of science. Hold your beliefs loosely. What this data set tells me in the context of everything that we have discussed to date is this: 1) Boosting with mRNA vaccines should be absolutely encouraged for all at risk and vulnerable persons, 2) The rest of us should choose based on personal fear and lifestyle to boost or get natural disease, 3) Unless this data set is different when looked at in humans, a Omicron specific vaccine has just lost steam for me, 4) The timing of boosting for at risk individuals is likely to be biannual for a significant level of protection, however, this has not been settled to my knowledge. This is my scientific hypothesis.

Watching BA.2,

Dr. M

Abramson American Psychological Association
Fitousi Frontiers Psychology
Brennan Gut
Keller NYTimes
Hall NEJM
Chauss Nature Immunology
Keeton MedRxIV
Xie Nature Medicine
Gagne BioRxIV
CDC MMWR
CDC Variants Page