August 16th, 2021
Delta is everywhere, check. Delta is far more contagious, check check. Delta is not killing at a higher rate so far and likely won't pending another mutation, check check check. Therefore, we need to keep our heads about the severity change. Lockdowns and school closures should not be on anyone's lips. The most important piece of data to pass along remains the knowledge that death is fleeting once vaccinated. Once previously recovered or vaccinated, memory T cells and B cells are working very well to prevent hospitalizations mostly and death almost completely. Mild breakthrough cases in vaccinated individuals are expected with waning immunity.
We know that people can get this virus multiple times as we do with the common cold. Lasting immunity to the coronaviruses appears to be good for severe disease but not so great for mild illness making infectious transfer a continued possibility and problem.
Reasonable immunity should be expected to be long lasting for SARS2 based on SARS1 history via T cell memory for convalescent post infected individuals.
We have the United Kingdom as a precursor to the likely trend of wave number 4. By mid September, this wave should be slowing down.
Our clinic has only had 3 significant COVID cases in children since the pandemic began with no deaths. Thus, the case for school closure is non existent from a morbidity and mortality perspective.
My current recommendations: 1) get vaccinated and take the guess work out of this. 2) You may want to wait 11 or 12 weeks in between doses for better lasting immunity according to European data. (Ledford H. 2021) 3) follow the links in the introduction above for an integrative approach to remaining immune solvent to reduce all cause infectious mortality risk. 4) live every day like it is your last by honoring your mission to be a great human while you love people around you and while you love yourself.
Memento mori.
Quick Hits:
1) If you have higher levels of neutralizing antibodies post vaccination and likely by extension post natural illness, your risk of a reinfection is exceedingly low. (Mallapaty R. 2021) Neutralizing antibodies are the antibodies that specifically prevent the virus from attaching to and infecting the cell rendering them non infectious. Thus, these antibodies are critical in the fight against pathogens. In previous studies with previous vaccine related responses, abnormal host microbiomes, stress, and other causes of immune dysregulation can ruin an immune response to a vaccination. (de Jong et. al. 2020)(Kiecolt-Glaser J. 2021)
Thus, as always it behooves us to sleep well and consistently around the period of vaccination. We should maintain an anti-inflammatory diet type to limit nutritional stressors and micronutrient insufficiencies that can sack your immune response. We absolutely should work on our innate stress and response to it. Esentially, following the same rules of healthy living to prevent covid from killing us also help us respond well to the vaccine.
2) Covid19 is truly affecting the brains of hospitalized individuals that undergo significant inflammation during and post infection. To survive the illness unfortunately leaves many individuals with residual neurological deficits that pathologically look like dementia. In multiple autopsy analysis, pathologists are finding that astrocytes, specific brain support cells, are being attacked and damaged leading to neuronal transmission dysfunction that we may see as brain fog, fatigue and memory loss. From Nature news, "In a second paper, published online last December, a team including Prüss studied the blood and cerebrospinal fluid of 11 people critically ill with COVID-19, all of whom had neurological symptoms12. All produced autoantibodies capable of binding neurons. And there is evidence that giving patients intravenous immunoglobulin, another type of antibody, to suppress the harmful autoantibodies’ action is “quite successful”, says Prüss. These pathways — astrocytes, pericytes and autoantibodies — are not mutually exclusive, and are probably not the only ones: it is likely that people with COVID-19 experience neurological symptoms for a range of reasons. Prüss says a key question is what proportion of cases is caused by each of the pathways. “That will determine treatment,” he says."(Marshall M. 2021)
The data keeps mounting higher and higher regarding the neurological side effects of natural SARS2 infection. If autoantibodies keep developing against our self tissue in response to the inflammation of immune response to SARS2, then we will see more acute and chronic disease manifestations in survivors of disease. In these cited studies above we see pathology specimens directly noting the affected regions and cells of the brain. We also see which other actions are contributing including pericyte blood flow loss and auto self reactive neuronal antibodies. Therefore, as with COVID in general, the virus and subsequent immune response causes damage to our cellular structures through multiple processes making treatment that much more difficult once the virus has established itself.
It will be unfortunate to see the volume of neurologic disease that follows the Delta variant in the unvaccinated and perviously not infected populations of Americans. We have clear evidence that it is happening. Now the big question is at what frequency and morbidity? With most of the at risk elderly and metabolically diseased Americans either having died or been vaccinated against SARS2, we are seeing a shift in disease incidence to the younger age. Thus, by definition we are going to see far less death and morbidity than all of the first three waves. However, we are now likely to see are large wave of mild post infectious complications by the stated pathways. To what degree remains to manifest itself.
Another article on COVID related cognitive deficits can be found here.
3) Variants continue to be a HOT and getting hotter topic - SARS2 Version B 1.617.2 Delta is now at 90% of US cases. Data for the delta variant is still showing significantly increased transmissibility. The mRNA vaccines are still working quite well. The breakthrough cases in vaccinated persons with the delta variant have been almost entirely asymptomatic with little to no risk of outcome negativity defined as death or severe disease. There are reports out of Israel that the mRNA vaccines are less effective 39% at preventing infections, however, they remain 88-91% effective at preventing hospitalizations and deaths respectively. This conflicts with the data out of the UK that remains at 88% for any symptomatic disease. (Jones R. 2021)
Here is another study looking at vaccine efficacy that is a little more sobering with regard to infection failures but still excellent results with hospitalization and death. "Although clinical trials and real-world studies have affirmed the effectiveness and safety of the FDA-authorized COVID-19 vaccines, reports of breakthrough infections and persistent emergence of new variants highlight the need to vigilantly monitor the effectiveness of these vaccines. Here we compare the effectiveness of two full-length Spike protein-encoding mRNA vaccines from Moderna (mRNA-1273) and Pfizer/BioNTech (BNT162b2) in the Mayo Clinic Health System over time from January to July 2021, during which either the Alpha or Delta variant was highly prevalent. We defined cohorts of vaccinated and unvaccinated individuals from Minnesota (n = 25,589 each) matched on age, sex, race, history of prior SARS-CoV-2 PCR testing, and date of full vaccination. Both vaccines were highly effective during this study period against SARS-CoV-2 infection mRNA-1273: 86%, BNT162b2: 76% and COVID-19 associated hospitalization mRNA-1273: 91.6%; BNT162b2: 85%. However, in July, the effectiveness against infection was considerably lower for mRNA-1273: 76% with an even more pronounced reduction in effectiveness for BNT162b2: 42%. Notably, the Delta variant prevalence in Minnesota increased from 0.7% in May to over 70% in July whereas the Alpha variant prevalence decreased from 85% to 13% over the same time period. Comparing rates of infection between matched individuals fully vaccinated with mRNA-1273 versus BNT162b2 across Mayo Clinic Health System sites in multiple states (Minnesota, Wisconsin, Arizona, Florida, and Iowa), mRNA-1273 conferred a two-fold risk reduction against breakthrough infection compared to BNT162b2. In Florida, which is currently experiencing its largest COVID-19 surge to date, the risk of infection in July after full vaccination with mRNA-1273 was about 60% lower than after full vaccination with BNT162b2. Our observational study highlights that while both mRNA COVID-19 vaccines strongly protect against infection and severe disease, further evaluation of mechanisms underlying differences in their effectiveness such as dosing regimens and vaccine composition are warranted." (Puranik et. al. 2021) The effectiveness of the Pfizer mRNA vaccine against the delta variant is 88% according to a study in the NEJM by Bernal et. al. 2021.
The take home point remains: Vaccines are effective even though the ability to prevent all infections and remain asymptomatic has taken a hit.
The DELTA VARIANT IS SIGNIFICANTLY MORE INFECTIOUS THAN THE ORIGINAL SARS2 STRAIN BUT NOT MORE DEADLY OVERALL. It appears to have viral loads a 1000x greater than the original strain. This is important to reflect upon. Until we see a huge uptick in mortality, we can safely assume that our overall risk for a problem once vaccinated even with a breakthrough case remains very very very small. History tells us that these pandemics are rarely if ever shifted into more deadly variants as this offers no advantage to the virus where the increase in spread provides a huge advantage. Remember that the virus only evolves to enhance its survival. Killing the host is not in any circumstance more advantageous.
Still zero evidence that the delta variant is more problematic to children at any age.
The lambda and gamma variants are not gaining any traction against the delta variant as the dominant player in the US.
4) In an excellent blog from the NEJM, Dr. Paul Sax makes quick work of the crazy situations related to Delta and vaccinated person breakthroughs. Here are some of the highlights: "These suggest that vaccinated people with COVID-19 could spread the virus to others as easily as unvaccinated people. It’s not proof, as it discounts the immune response, which may dampen contagious virus and shorten the duration of viral shedding. It’s also in contrast with other studies that do show lower viral burdens over time in people who have been vaccinated." "Regardless, it underscores the plain fact that anyone with symptoms consistent with COVID-19 needs to isolate until recovery, vaccination status notwithstanding. For those diagnosed, we may even need to institute different isolation protocols, since the higher viral loads seen with Delta could mean more transmissions further out from onset of symptoms. Already, the CDC has recommended that vaccinated people exposed to COVID-19 should get tested afterward, a return to pre-vaccine guidance. Should we also recommend antigen testing in breakthrough cases before return to work? (PCR may continue to detect non-viable viral fragments long beyond the contagious phase.) What the outbreak can’t tell us is how bad this would have been without vaccines at all. Yes, there were lots of cases, but so far relatively few hospitalizations, and no deaths. Yikes, the mind boggles." "Get as many eligible people vaccinated as possible. Remember, the vaccines reduce transmission risk in two ways:
1. Decreasing the probability of infection in the first place, either symptomatic or asymptomatic
2. Decreasing the duration of infectiousness for those who do get infected
That first effect is ironclad — no virus, no transmission. The second one is a bonus. The evidence is strong that both of these are in play with COVID-19 vaccines". (Sax P. 2021)
The massive TAKE HOME POINT again here is this: the vaccines are working well for Delta and all of the variants! Death is not happening and hospitalizations remain rare after 2 dose series of vaccines. Otherwise, Delta as we are seeing is a major contagious nightmare that is now more transmissible that Smallpox, Influenza, Sars1/Mers1 and on par/slightly less than with Chicken pox. Only Measles is a worse train wreck infectiousness wise. The R0, reproduction rate, for these infections is 1-2 for influenza meaning for every 1 infected person,1 to 2 others will be infected. For Sars2 alpha that number was 3. Now SARS2 delta is at around a 6. Chicken pox is a 10 and measles is a 12+. Therefore, for SARS2 delta for every infected person, 6 will be infected. Then those 6 will infect 6 more and on and on. This is exponential and explains why a R0 of 2 is nowhere close to the infectiousness of a 6 and way less than a 12.
Here is how it looks numerically:
1 infected person with: flu infects 2, SARS2 alpha 3, SARS2 delta 6, Chicken pox 10 and Measles 12.
then those infected people with: flu infect 4, SARS2 alpha 9, SARS2 delta 36, Chicken pox 100 and Measles 144.
then those infected people with: flu infect 8, SARS2 alpha 27, SARS2 delta 216, Chicken pox 1000 and Measles 1728.
then those infected people with: flu infect 16, SARS2 alpha 81, SARS2 delta 1296, Chicken pox 10000 and Measles 20736.
These numbers are sobering! The variant jump in infectiousness for the alpha and delta variants goes from 81 to 1296 cases by the end of four events. That is a wildfire. The only silver lining is that morbidity is not worse.
5) Masking question from a reader. Hi. I am on the BOD for the new charter school in .............. We met last night to discuss whether to require masks for students for the first thirty days of school. One argument made against masks was that kids are breathing in too much carbon dioxide and the deprivement of oxygen is not beneficial for brain development in children. Our grades are K-7. I wondered if you have any information/research on this theory. Thanks for any help you can provide! I am trying to make the best decision for our students.
My response: Thoughtful question. Difficult answer. While the risk of a bad outcome remains incredibly low at this age, it is not zero as death is at 0.01% for the very young children which is similar to the flu for this group. The issues start to creep in more in the later teenage years although still very small. Masking in school makes sense at this point for all ages until this wave blows over. The delta variant is a different animal altogether with a reproductive rate of 6 which is twice as high as the alpha variant.
The risk of CO2 overload is not scientifically proven to be clinically relevant. The simple solution for me would be to compromise and be proactive by taking a break every hour and go outside where kids can be mask free for 5 minutes socially distanced talking in groups. The kids will love the socialization, which they need, and hopefully this will appease all parties.
The first rule for me is do no harm. I think that we do not have that luxury anymore with COVID as we are always losing a little somewhere whether it be socially, academically. societally, medically, mentally, etc... We do the best that we can and pray for a great outcome.
When looking through the research, I could find no solid evidence of risk even in healthcare workers using N95 masks which are much more difficult on CO2 expulsion than the traditional mask.
I hope that this helps you,
Dr. M
I also asked Dr. Danny Benjamin again what his thoughts are about universal masking now that Delta is here and we are in high volume of disease. His response, we need to universally mask for now. Read his Op Ed in the New York Times at this link.
He also stated that he thinks that vaccination of athletes will help these teens continue to play sports.
6) Repeat based on importance in case anyone missed it last time: A few people are asking about the need to vaccinate if you have already had COVID natural illness. What is the story here? Hot off of the press from Cell Reports Medicine, we see: "Ending the COVID-19 pandemic will require long-lived immunity to SARS-CoV-2. Here, we evaluate 254 COVID-19 patients longitudinally up to 8 months and find durable broad-based immune responses. SARS-CoV-2 spike binding and neutralizing antibodies exhibit a bi-phasic decay with an extended half-life of >200 days suggesting the generation of longer-lived plasma cells. SARS-CoV-2 infection also boosts antibody titers to SARS-CoV-1 and common betacoronaviruses. In addition, spike-specific IgG+ memory B cells persist, which bodes well for a rapid antibody response upon virus re-exposure or vaccination. Virus-specific CD4+ and CD8+ T cells are polyfunctional and maintained with an estimated half-life of 200 days. Interestingly, CD4+ T cell responses equally target several SARS-CoV-2 proteins, whereas the CD8+ T cell responses preferentially target the nucleoprotein, highlighting the potential importance of including the nucleoprotein in future vaccines. Taken together, these results suggest that broad and effective immunity may persist long-term in recovered COVID-19 patients." (Cohen et. al. 2021)
This builds upon other studies finding very good long term memory B and T cell responses after natural infection especially with increasing severity of the natural illness. This means that in most cases, you are well protected from COVID after a natural infection. However, some RARE individuals will have a low antibody response and may also mount a weaker immune response the second time around as has been shown in some cases. Predicting who these individuals are is not possible at this time on a population basis. Thus, there is a reasonable argument for COVID naturally infected individuals to get one booster dose of an mRNA vaccine to insure a quality response immunologically upon preexposure to the virus. I cannot find any reasonable data or reason to get a two dose series in these people. (Krammer F. et. al. 2021)(Saadat et. al. 2021)(Abu Jamal et. al. 2021) More on the "Do you need a second vaccine dose" if you know that you had COVID already naturally? Now we have a longitudinal study that also finds that the second dose has no added benefit for those persons in the convalescent phase of SARS2. They looked specifically at the T cell response and found that: "Vaccine-elicited spike-specific T cells responded similarly to stimulation by spike epitopes from the ancestral, B.1.1.7 and B.1.351 variant strains, both in terms of cell numbers and phenotypes. In infection-naïve individuals, the second dose boosted the quantity but not quality of the T cell response, while in convalescents the second dose helped neither. Spike-specific T cells from convalescent vaccinees differed strikingly from those of infection-naïve vaccinees, with phenotypic features suggesting superior long-term persistence and ability to home to the respiratory tract including the nasopharynx." (Neidleman et. al. 2021)
If you had natural infection and received one dose of a COVID vaccine, the T cell function and by definition your outcome if re-exposed again looks great. Thus, it makes logical sense now to prioritize vaccinating the global population with appropriate doses based on known convalescent history.
Dr. M
Ledford Nature
Mallapaty Nature News
de Jong Cell Host Microbe
Kiecolt-Glaser OSU Medical School
Bergwerk NEJM
Bernal NEJM
Puranik MedRxIV
Marshall Nature News
Sax NEJM
Cohen Cell Reports Medicine
Krammer NEJM
Saadat JAMANetwork
Abu Jabal Euro Surveill
Neidleman MedRxIV
Li Virological
Jones Wall Street Journal
CDC MMWR
CDC Variants Page
Reardon Nature
National Geographic has a comprehensive article on the delta variant. LINK
