Coronavirus Update 45
September 27th, 2021
Wave four is over in our clinic as our test positivity rate has plummeted from the 30% range to less than 5%. We had a four week run of high volume COVID incidence with minimal moderate to almost no severe disease in kids. This is a blessing as the delta variant was a question mark for a little while there.
The best answer to slowing down the pandemic remains vaccination as we are now living in a world where hospitals have been overwhelmed leaving ICU beds unavailable. This is not just a covid unvaccinated person problem as I have had some people tell me.
The ICU's are meant for all patients as the need arises, thus, if an ICU is filled with covid unvaccinated patients, then others may die of a non covid related disease which is a mess of grand proportions. Please reconsider your stance on vaccination if you remain on the fence. I have now seen too many unvaccinated parents leave my patients missing a parent. This is tragic and sad.
Dr. Rhonda Patrick and Dr. Roger Sheheult have a great youtube video on vaccine and side effects for anyone who still needs more data to inform their choice. One point that they make that is very explicit and akin to risk stratification discussions that I have had in the past year is as follows:
584,000 people over 50 years of age have died from COVID most of which had a co-morbid disease. 5000 not verified deaths were attributed to COVID vaccine via the VAERS reporting system which is a voluntary vaccine reporting system. That is roughly 120x more deaths from covid than vaccine assuming all reported deaths were truly from the vaccine. Straight math to see the worse risk category. For individuals aged 40 to 49, there were 20000 covid deaths and 200 vaccine reported deaths, 100x difference. For 18 to 30 years of age there were 10000 covid deaths and 200 vaccine reported deaths. 50x difference.
In medicine, we use drugs every day with small but real risk. Vaccines are no different. We are making calculated risks everyday with every decision.
The Pfizer vaccine study in children 5 to 11 years of age has preliminarily topline evidence for safety and immunogenicity as reported this week. The FDA has not reviewed the data. The company is reporting similar results for safety and immunogenicity compared to the 16-25 year old cohort. We cannot run the same analysis as above as we do not have VAERS data for this group yet.
According to the American Academy of Pediatrics, to date there have been 480 deaths in children by state based data. This data is for children aged 0 to 14-19 years based on the states reporting measures. That is a sad but small number overall compared to all other age demographics. More to come.
As it stands today, the United States has had 43 million known cases and almost 688,000 deaths. This number is greater now than the flu pandemic of 1918. 675,000 Americans were said to have died during the pandemic over the 1918-1919 timeframe. For me, this is a gross reflection on the abject lack of health across the United States for a large swath of society. The poor metabolic health of our citizens is the direct cause of our universally worse world comparable outcomes. I suspect that if the 1918 flu came back today, we would see more deaths overall based on our health parameters.
Quick Hits -
1) Vaccination may offer a reduction in in house spread from the vaccinated to the remainder of the household. "Cases of Covid-19 were less common among household members of vaccinated health care workers during the period beginning 14 days after the first dose than during the unvaccinated period before the first dose (event rate per 100 person-years, 9.40 before the first dose and 5.93 beginning 14 days after the first dose). After the health care worker’s second dose, the rate in household members was lower still (2.98 cases per 100 person-years)." Vaccination was associated with a reduction in both the number of cases and the number of Covid-19–related hospitalizations in health care workers between the unvaccinated period and the period beginning 14 days after the first dose. (Shah et. al. 2021) This is not surprising as many vaccinated persons will not bring home the virus nor propogate its movement within a house.
2) "Of 105 446 unique pregnancies, 13 160 spontaneous abortions and 92 286 ongoing pregnancies were identified. Overall, 7.8% of women received 1 or more BNT162b2 (Pfizer-BioNTech) vaccines; 6.0% received 1 or more mRNA-1273 (Moderna) vaccines; and 0.5% received an Ad26.COV.2.S (Janssen) vaccine during pregnancy and before 20 weeks’ gestation. The proportion of women aged 35 through 49 years with spontaneous abortions was higher (38.7%) than with ongoing pregnancies (22.3%). A COVID-19 vaccine was received within 28 days prior to an index date among 8.0% of ongoing pregnancy periods vs 8.6% of spontaneous abortions. Spontaneous abortions did not have an increased odds of exposure to a COVID-19 vaccination in the prior 28 days compared with ongoing pregnancies. Results were consistent for mRNA-1273 and BNT162b2 and by gestational age group" (Kharbanda et. al. 2021)
This is another large multi center trial showing no risk of negative post vaccine neonatal outcome.
3) How to super charge your immunity? In a recent study in MedRxIV, Dr. Bieniasz and colleagues have noted a robust immune response in naturally infected individuals who were subsequently vaccinated with an mRNA vaccine. "Strikingly however, plasma from individuals who had been infected and subsequently received mRNA vaccination, neutralized this highly resistant SARS-CoV-2 polymutant, and also neutralized diverse sarbecoviruses. Thus, optimally elicited human polyclonal antibodies against SARS-CoV-2 should be resilient to substantial future SARS-CoV-2 variation and may confer protection against future sarbecovirus pandemics." (Schmidt et. al. 2021) This study was industry funded making the conclusions biased, however, the science appears solid and in line with other studies looking at a similar response. The thrust of the study is that natural disease followed by a dose of Pfizer's mRNA vaccine allows the human immune system to have highly effective immunity against variants including a poly mutant with significant resistance genes.
The take home point is: based on this study, prior natural infection plus a vaccine dose provides highly effective immunity against current variants and likely against the future as well. This may be a great path forward for many individuals willing to get a single dose of mRNA vaccines post natural disease.
4) Mutli inflammatory syndrome data: Incidence is exceedingly rare. 316 persons per 1 000 000 SARS-CoV-2 infections in persons younger than 21 years developed MIS. Incidence was higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons compared with White persons and in younger persons compared with older persons. (Payne et. al. 2021)
For the clinician readers: Ed Behrens' group at the Children's Hospital of Philadelphia looked at twenty patients, 9 with severe COVID-19, 5 with minimal COVID-19, and 6 with Multi inflammatory Syndrome-C. Five cytokines (IFN-γ, IL-10, IL-6, IL-8, and TNF-α) contributed to the analysis. TNF-α and IL-10 discriminated between patients with MIS-C and severe COVID-19. The presence of burr cells on blood smears, as well as Cts, differentiated between patients with severe COVID-19 and those with MIS-C. (Diorio et. al. 2020)
5) Boots on the ground - No increase incidence of MIS or deaths in children noted by my friends in Charlotte, Charlottesville, Raleigh and Philadelphia. There are many more cases in children which is expected with a more infectious viral variant. Adult disease continues to be mostly in unvaccinated individuals with a co morbidity or vaccinated individuals over 65 years with comorbid disease. The theme of inflammation and age continues true.
6) Paul Nurse has written a brilliant piece that all should read in the Journal Nature. "Rather often, I go to a research talk and feel drowned in data. Some speakers seem to think they must unleash a tsunami of data if they are to be taken seriously. The framing is neglected, along with why the data are being collected; what hypotheses are being tested; what ideas are emerging. Researchers seem reluctant to come to biological conclusions or present new ideas. The same occurs in written publications. It is as if speculation about what the data might mean and the discussion of ideas are not quite ‘proper’. I have a different view: description and data collection are necessary but insufficient. Ideas, even tentative ones, are also needed, along with the recognition that ideas will change as facts and arguments accumulate.
Why are researchers holding back on ideas? Perhaps they are worried about proposing an idea that turns out to be wrong, because that might damage their chances of getting promotion or funding. But as Charles Darwin put it: “False facts are highly injurious to the progress of science, for they often endure long; but false views, if supported by some evidence, do little harm, for everyone takes a salutary pleasure in proving their falseness; and when this is done, one path towards error is closed and the road to truth is often at the same time opened.” To wit, it’s important to get the facts right, but new ideas are useful, as long as they are based on reasonable evidence and are amenable to correction." (Nurse P. 2021)
This commentary leads back into last weeks commentary on physician and provider censorship. Thought and discourse remain the key to successful scientific advancement. The onus should be upon the messages to be honest and truthful to the best of each persons's knowledge. However, blanket censorship statements to all physicians and providers of care and or threats of licensure removal are completely unhelpful in any reasonable society.
7) Science heavy: "Regulatory T cells (Tregs) are responsible for restraining excessive inflammation, a hallmark of COVID-19. We identified a striking phenotype in Tregs from patients with severe disease, as well as an interesting role for interleukin (IL)-6 and IL-18. An increased suppressive profile, including increased Treg proportions, combined with the expression of proinflammatory mediators, distinguished severe patients and persisted in some of those recovered. This phenotype is in notable similarity to that found in tumor-infiltrating Tregs, which are generally associated with poor prognosis, and suggests both a detrimental role for these cells in COVID-19 as well as a potential explanation for some of the still largely unexplored complications associated with recovery." (Galvan-Pena et. al. 2021) This is a really interesting study in so far as it notes that T regulatory cells are over represented and over express a suppression state that turns down the anti viral killing cytokines. This is largely confusing as Vitamin D along with vitamin A and commensal gut microbiota are involved in enhancing T reg activity system wide.
There was a large body of evidence linking low vitamin D levels and worse outcomes post SARS2 infection leading many people to increase vitamin D intake during the pandemic. However, this study is showing the exact opposite. Or maybe the truth is that at either extreme, T reg function is altered and immune based viral killing capacity is hampered. We still have more questions than answers and keep peeling the onion to find more layers of learning to be understood.
8) FDA advisory Panel votes against a third COVID vaccine for all. They target the older population, over 65 years, as well as those with high risk disease states that involve immune suppression. This makes complete sense as the vaccines are still working great for preventing hospitalization and death.
Common sense prevails!
• CDC has come up with a different plan: CDC recommends that the following groups should receive a booster shot of Pfizer-BioNTech’s COVID-19 Vaccine at least 6 months after completing their Pfizer-BioNTech primary series (i.e., the first 2 doses of a COVID-19 vaccine):
• people aged 65 years and older
• residents aged 18 years and older in long-term care settings
• people aged 50–64 years with underlying medical conditions
• CDC also recommends that the following groups may receive a booster shot of Pfizer-BioNTech’s COVID-19 Vaccine at least 6 months after completing their Pfizer-BioNTech primary series, based on their individual benefits and risks:
• people aged 18–49 years with underlying medical conditions
• people aged 18–64 years at increased risk for COVID-19 exposure and transmission because of occupational or institutional setting
• These recommendations only apply to people who previously received a Pfizer-BioNTech primary series (i.e., the first 2 doses of a COVID-19 vaccine).
• People can talk to their healthcare provider about whether getting a Pfizer-BioNTech COVID-19 booster shot is appropriate for them. (CDC.Gov)
9) Interesting article on 5 countries eschewing restrictions in favor of a "live with covid" strategy. Link. These countries and likely soon to be more will be a roadmap for slow adopters of change worldwide.
10) Risk of a third shot or booster? We have little to no data so far. In STAT news, there is a speculative article discussing some thoughts on risk. (Joseph A. 2021)
Layer your protection,
Diorio J Clinical Investigation
Galvan Pena PNAS
CDC Variants Page