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 February 13th, 2023

 variants make up: BQ.1 is 5%, BQ1.1 is 15%, XBB1.5 is 75% and XBB is 2%

XBB.1.5 remains the dominant strain where there was no increased risk of hospitalization or death in countries like Singapore where data has been tracked.

None of these VOC's are showing signs of increased disease morbidity.

Little else to report here. (CDC Variants)

Stay Tuned

Quick Hits and other musings -

1) An article in Nature Cell Research notes that repeated vaccination with Sars2 vaccine leads to worsened neutralizing antibody responses to Omicron variants. "Our data suggest that repeated vaccination with inactivated virus vaccine back-boosts previous memory and dampens the immune response to a new antigenically related but distinct viral strain. Such vaccination-induced immune imprint could reflect the “original antigenic sin” doctrine described in the influenza field, whereby individuals infected with a new circulating viral strain developed a strong immune response to a priorly exposed strain." (Gao et. al. 2023)

Yet more evidence that boosting with the bivalent vaccine offers little to less than little benefit for all but the high risk individuals. Choose wisely. This appears to be a period when natural infection for most is likely to be the only logical route moving forward.

2) From a large meta analysis regarding masking use and benefits we see: "The pooled results of RCTs did not show a clear reduction in respiratory viral infection with the use of medical/surgical masks. There were no clear differences between the use of medical/surgical masks compared with N95/P2 respirators in healthcare workers when used in routine care to reduce respiratory viral infection. Hand hygiene is likely to modestly reduce the burden of respiratory illness, and although this effect was also present when ILI and laboratory‐confirmed influenza were analysed separately, it was not found to be a significant difference for the latter two outcomes. Harms associated with physical interventions were under‐investigated. There is a need for large, well‐designed RCTs addressing the effectiveness of many of these interventions in multiple settings and populations, as well as the impact of adherence on effectiveness, especially in those most at risk of ARIs." (Jefferson et. al. 2023)

I find Vinay Prasad's commentary on this reality amusing and sad all at the same time. He states: "It is irrational to mask. At best you marginally delay the inevitable, and unlike pre-vax, there is no milestone you are waiting for. Let’s take a closer look....Here is the big summary finding. With 276,000 participants in RCTs or cluster RCTs, masking does nothing. No reduction in influenza like or Covid like illness and no reduction in confirmed flu or COVID. That’s stone cold negative. See those effect sizes and confidence intervals." I remember thinking how ridiculous it was that we were asking 2-5 year olds to mask in clinic, restaurants and so on. None of them ever wore the mask correctly for any length of time, parents were frustrated and the benefit was known to be minimal at best, if at all. And worse, we had no idea of the psychological ramifications of a fear based approach to disease mitigation in the very young. Time will tell how badly our misguided masking policies have affected our children.

I still mask in sick clinic primarily for the event where a child directly coughs in my face or what I call a massive pathogen transfer. The mask likely reduces the viral load of exposure if I do get exposed and or sick. However, that is my choice and it works for me. A global mask policy has little to no merit in the general community outside of a hospital setting.

3) From JAMA we have a comprehensive data set on death in children: "There were 821 COVID-19 deaths among individuals aged 0 to 19 years during the study period, resulting in a crude death rate of 1.0 per 100,000 population overall; 4.3 per 100,000 for those younger than 1 year; 0.6 per 100,000 for those aged 1 to 4 years; 0.4 per 100,000 for those aged 5 to 9 years; 0.5 per 100,000 for those aged 10 to 14 years; and 1.8 per 100,000 for those aged 15 to 19 years. COVID-19 mortality in the time period of August 1, 2021, to July 31, 2022, was among the 10 leading causes of death in CYP aged 0 to 19 years in the US, ranking eighth among all causes of deaths, fifth in disease-related causes of deaths (excluding unintentional injuries, assault, and suicide), and first in deaths caused by infectious or respiratory diseases when compared with 2019. COVID-19 deaths constituted 2% of all causes of death in this age group.....In 2019, leading causes of CYP deaths were perinatal conditions (12.7 per 100,000), unintentional injuries (9.1 per 100,000), congenital malformations or deformations (6.5 per 100,000), assault (3.4 per 100,000), suicide (3.4 per 100,000), malignant neoplasms (2.1 per 100,000), diseases of the heart (1.1 per 100,000), and influenza and pneumonia (0.6 per 100,000). For comparison, in the study period, August 1, 2021, to July 31, 2022, there were 821 CYP deaths reported for which the underlying cause was COVID-19 (1.0 per 100,000), meaning COVID-19 ranked as the eighth leading cause of death and accounted for 2.0% of all causes of death. "(Flaxman et. al. 2023)

What is missing in this data set as published is the groups that were at risk for death based on each age stratification. How many of these children had a comorbidity? I suspect that it is the vast majority. This information would be very useful in helping to stratify which children need vaccination and or boosting. Covid death in children is similar in risk to influenza and pneumonia outside of the 0 to 1 year old age range where the risk appears to higher for covid under 1 year of age. Since vaccination is only available at 6 months and older, are we really discussing a 6 month window of protection? So many questions and not enough data based answers.

Outside the children with co morbidity, having more risk stratified data would help to ascertain which children need to vaccinate in this early phase of life. Yet, we remain in the dark to the data that organizations are holding and not publishing, even this study is opaque to why a covid death occurred for a given age. A major frustration for me. Remember that the vaccine offers little to no transmission protection, thus it is only death that we are protecting against in that child.

The final answer is that the only group, other than those with a known comorbidity, that currently is at significant risk is the 0 to 1 year olds leaving these parents to choose to vaccinate or not based on their risk tolerance of 4.3 deaths per 100,000 children.

4) We have looked at learning before and most if not all data showed a major slowing of learning in the US especially in low income children and heavily slanted towards math deficits. In a new meta analysis in Nature: "Our meta-analysis suggests that learning progress has slowed substantially during the COVID-19 pandemic. The pooled effect size implies that students lost out on about 35% of a normal school year’s worth of learning. This confirms initial concerns that substantial learning deficits would arise during the pandemic. But our results also suggest that fears of an accumulation of learning deficits as the pandemic continues have not materialized. On average, learning deficits emerged early in the pandemic and have neither closed nor widened substantially."(Betthauser et. al. 2023)

This is somewhat good news, if repeated in further studies, that the deficits did not stack upon themselves leading to further long term educational losses on top of the knowns.

5) Information looking at Ecohealth Alliance and the NIH's oversight was recently discussed in the NYtimes. (Mueller et. al. 2023)

6) Finally, an article looking at lifestyle choices and post covid long term sequelae risk. From JAMA Internal Medicine: "Results: A total of 1981 women with a positive SARS-CoV-2 test over 19 months of follow-up were documented. Among those participants, mean age was 64.7 years; 97.4% were White; and 42.8% were active health care workers. Among these, 871 (44.0%) developed PCC. Healthy lifestyle was associated with lower risk of PCC in a dose-dependent manner. Compared with women without any healthy lifestyle factors, those with 5 to 6 had 49% lower risk of PCC. In a model mutually adjusted for all lifestyle factors, BMI and sleep were independently associated with risk of PCC. If these associations were causal, 36.0% of PCC cases would have been prevented if all participants had 5 to 6 healthy lifestyle factors. Results were comparable when PCC was defined as symptoms of at least 2-month duration or having ongoing symptoms at the time of PCC assessment. (Wang et. al. 2023)

The six factors of lifestyle that were measured were: Body mass index, smoking, alcohol consumption, diet, physical activity, and sleep. I would have loved another variable - stress of the mind. See below for a breakdown of the lifestyle factors.

What this study indicates is the reality that we have discussed for years, taking care of oneself reduces systemic inflammation and thereby viral induced pathogenesis. This study is critical to stemming the tide of prolonged Covid related pathology and health span reductions.

7) Massive problem on the horizon for patients of healthcare: "One report estimated that in 2021 alone, about 117,000 physicians left the work force, while fewer than 40,000 joined it. This has worsened a chronic physician shortage, leaving many hospitals and clinics struggling. And the situation is set to get worse. One in five doctors says he or she plans to leave practice in the coming years." (Rinehart E. 2023)

Burnout is real for medical providers based on a system that prizes money over patient health. I am living this real time as we extricate ourselves from organizations that waste money and wonder why we are frustrated that the children are not receiving the services that they need and deserve. Read the entire NYT article as it is real and will be a part of our lives moving forward. Quality in medical providers is going down as the older more wise providers leave and are not replaced or partially replaced with a less knowledgeable generation of providers still in learning mode. I fear for those that are not as lucky as I am to know who is a quality provider for my friends and family. This is real folks.

8) In a large Canadian study in the BMJ, we see strong efficacy of mRNA vaccines against infants getting ill with Covid after delivery. The problem with using this study moving forward is two fold: 1) now that everyone has natural or vaccine induced immunity, does maternal vaccination help the infant now in this new landscape? 2) The statistics show that in total, 29 (29%) of 99 infants were admitted to hospital because of a delta infection and 330 (22%) of 1501 infants were admitted to hospital because of an omicron infection. (Jorgensen et. al.. 2023) How sick did they get? Were they admitted as a precaution based on age with little to no illness which is a common event for fever in a newborn? This matters tremendously as morbidity would drive me to want to vaccinate a mother for her child. However, if the morbidity is limited and/or minimal, then that calculus changes. This question needs to be further analyzed before solid recommendations can be made.

Maternal vaccination is noted to be associated with reduced maternal risk which is great. However, I ask the question again how this truth holds up in the new XBB and other omicron variant world?

 

That's all this week!

Dr. M

Gao Nature Cell Research
Jefferson Cochrane Review
Prasad Substack
Flaxman JAMA
Betthauser Nature
Mueller NYTimes
Chemaittely NEJM
Bobrovitz Lancet ID
Wang JAMA Internal Medicine
Rinehart NYTimes
Jorgensen BMJ
CDC MMWR
CDC Variants Page
CDC Covid Deaths

"Six potentially modifiable lifestyle factors were assessed, including BMI, smoking, alcohol consumption, diet, physical activity, and sleep (2015 for diet and alcohol intake, 2017 for others). Self-report of weight and height has been validated in this cohort.26 Smoking was queried every 2 years, and we characterized lifetime smoking history as never, past, or current smoking. In a validation study, toenail nicotine level was strongly associated with reported smoking level (Spearman r, 0.63).27 Diet in the past year was measured using a validated semiquantitative food frequency questionnaire (FFQ).28,29 To characterize overall diet quality, we used the Alternative Healthy Eating Index (AHEI-2010), which is based on empirical evidence30 (higher score indicates healthier diet), excluding the alcohol component. Alcoholic beverage consumption was also collected by the FFQ. Physical activity was assessed using a validated questionnaire.31 For each participant, we estimated the average time spent in the past year in moderate to vigorous recreational activities (eg, running, jogging, cycling, tennis, squash, racquet ball, swimming, weight or resistance training, brisk walking, and other vigorous activities). We queried average sleep in a 24-hour period, with response options ranging from less than 5 to at least 10 hours. Daily sleep duration has been validated.32" (Wang et. al. 2023)