Spetember 13th, 2021

My current recommendations remain: 1) get vaccinated and take the guess work out of this as vaccination dramatically reduces death and hospitalization risk. 2) follow the links in the introduction above for an integrative approach to remaining immune solvent to reduce all cause infectious mortality risk. 3) 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.

As you will see this week, the data is often directionally the same but can go in the opposite direction making recommendation making a chore. I am falling back own a few generalized truisms. For 99% of us two paths exist that make sense, if you had a prior infection, then one vaccine booster is likely a perfect place to settle on based on the data or if you have no prior COVID history of infection, then 2 doses of mRNA vaccine for risk reduction even if you are healthy to prevent the rare healthy person bad outcome. if you have advanced age or a comorbid disease, boosters may and are likely to be useful in your future.

Quick Hits -

1) New Variant of interest is emerging around the globe. A new variant for now called C.1.2 has been detected in South Africa and a few other places. We will be watching this player as it has more mutations than the average variant that COULD confer increased transmissibility and vaccine breakthrough. On paper this appears to be likely, however, in vivo reality is often very different as this variant will have to compete with Delta in order to gain a foothold. Stay tuned. (Scheepers et. al. 2021)

2) More on breakthrough infections: " SARS-CoV-2-naïve vaccinees had a 13.06-fold increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant for symptomatic disease as well. When allowing the infection to occur at any time before vaccination (from March 2020 to February 2021), evidence of waning natural immunity was demonstrated, though SARS-CoV-2 naïve vaccinees had a 5.96-fold increased risk for breakthrough infection and a 7.13-fold increased risk for symptomatic disease. SARS-CoV-2-naïve vaccinees were also at a greater risk for COVID-19-related-hospitalizations compared to those that were previously infected." Gazit et. al. 2021)

We also know that cases are worse when a person has low circulating antibodies against SARS2 which happens particularly with advancing age. In my mind, having a comorbid disease and/or advanced age put you in a higher risk category for breakthrough infections and disease risk. See more with next piece.

3) Some research really puts a monkey wrench into data consolidation and thought formulation. But, alas, this is the world of science and it is grey folks. In a paper just published in Nature, Dr. McDade and colleagues report that:" We document lower levels of inhibition of spike-ACE2 binding for emerging variants of concern, and significant reductions in anti-RBD IgG and surrogate neutralization of all variants 3 months after a first mRNA vaccine dose. Consistent with a recent report, we find stronger vaccine responses following prior PCR-positive SARS-CoV-2 infection. Importantly, these stronger responses were limited to participants with PCR confirmed cases of COVID-19, and were not seen among those who did not experience symptoms or were seronegative. A large proportion of SARS-CoV-2 infections are asymptomatic, and our results indicate that seropositivity alone is not sufficient to predict a robust antibody response to vaccination. Recent data suggest that lower responses to vaccination are associated with increased risk of breakthrough infection: Among vaccinated healthcare workers in Israel monitored from January to April 2021, neutralizing antibody and anti-spike IgG titers were significantly lower in workers with breakthrough infections in comparison with matched, uninfected controls. The B.1.1.7 variant was detected in 85% of the breakthrough infections. While antibody neutralization of emerging variants may be reduced in comparison with the ancestral strain of SARS-CoV-2, T cell reactivity following vaccination or natural infection has been shown to be similar across strains and may reduce the severity of COVID-19 if a breakthrough infection occurs. The decline in antibody levels over three months post-vaccination, and the relatively reduced neutralization of variants of concern, point to an urgent need to identify correlates of clinical protection to inform the timing of and indications for booster vaccination." (McDade et. al. 2021)

Breaking this down. If you had a COVID positive test in the past but had little to no symptoms, your immune response from a long term antibody generation and duration perspective is not great long term. So the risk of a reinfection is higher by a significant margin. This is just like the typical circulating common cold corona viral strains. However, individually, this means that your immune system in general handles the virus well as it did the first time and likely will again. The kicker here remains for those with advanced age and comorbidity, the delta variant and future variants may change this narrative. Therefore, yet again, I would recommend vaccination to mitigate risk.

4) A Johns Hopkins' Study notes: "Our results demonstrated the durability of spike antibodies to SARS-CoV-2 up to 10 months after natural infection. The Centers for Disease Control and Prevention acknowledges that prior SARS-CoV-2 infection reduces the risk of reinfection for a minimum 90-day period. Our data demonstrate durability of IgG titers well beyond this period and extend recently published intervals of 6 to 8 months." (Egbert et. al. 2021) As with the above study, the antibody response and durability must be significantly tied to severity of infection and also individual host immune responses making a generalization about risk very hard to ferret out.

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) In a well written opinion piece from the NYTimes we see logical questions around our failed messaging around policy moving forward. "Another hard question that is most likely also causing confusion and disagreement is how we define “severe” disease in children. Children can get Covid, but their death and hospitalization rates are much lower than for adults. The inflammatory syndrome MIS-C is rare. Long Covid has gained wide attention, but recent studies have shown that rates are low among children and not dissimilar to effects caused by other viral illnesses. We’re not being cavalier by raising these points. Consider that in Britain the government doesn’t require masks for children in schools, and it’s not clear it will advise kids to get vaccinated, either. Britain has experts, as we do, and they are looking at the same scientific data we are; they most assuredly care about children’s health the same way we do, and yet, they have come to a different policy decision. Schools were prioritized over other activities, and the risks of transmission without masks were considered acceptable." (Allen J. 2021)

If I were in charge of the national message, which I never will be mind you, I would give one paramount directive. Kids must be in in person school no matter what save for one caveat. If a hospital system gets overwhelmed or appears to be getting there, the hospital system must notify the state which then notifies schools to prepare for a 2 week pause in in person learning to help decrease these events. This is assuming that there is widespread covid activity in said schools as we are seeing now. In no way can we ever return to full poor quality virtual learning. I would also recommend that if a 2 week pause occurs, that the school adds 2 weeks of learning tacked onto the end of the semester to complete all learning and offer remedial education. Education must be top on the priority list at this point in my opinion. Education is the staple for a healthy society to thrive and maintain mental solvency. I am exceedingly sad for all COVID deaths and long term symptoms, however, we have an effective vaccine that significantly reduces these risks. Thus, we cannot sacrifice the children's mental health and welfare anymore based on a choice that causes self harm.

There is now another big issue: censorship. I, and all of my colleagues, have just received an email that may change my ability to give an opinion on these topics which I find to be anti-american, anti-the first amendment and anti-medicine. While, I agree wholeheartedly that vaccines are effective and safe, I am one hundred percent in favor of free speech. Opinions and discourse are the only truths in medicine. We have seen so many times how medicine has been wrong about many topics. Alas, these are different times and I hope that the powers that be revert back to common sense and allow discourse. See below for the letter. It is a really difficult time for all of us in medicine as the person or people that get to decide what is misinformation may not align with truth in the long run as we have learned with the Lab leak theory and many other realities like lock downs. This is very disconcerting and not great for all of us. A pandemic and medicine in general are very fluid systems that lend poorly to hard truths. We must let the science speak.

7) There is no new information on boosters. I like this 7 reason list for why boosters are unlikely to be necessary. Monika Ghandi is an Infectious Disease specialist at UCSF in California and a well read author published this list in Mashup MD.
REASON #1: Memory B Cells Are Produced By Vaccines and Natural Infection
REASON #2: Memory B Cells Can Produce Neutralizing Antibodies If They See Infection Again Decades Later
REASON #3: Vaccines or Natural Infection Trigger Strong Memory T Cell Immunity
REASON #4: T Cell Immunity Following Vaccinations for Other Infections Is Long-Lasting
REASON #5: T Cell Immunity to Related Coronaviruses That Caused Severe Disease is Long-Lasting
REASON #6: T Cell Responses from Vaccination and Natural Infection With the Ancestral Strain of COVID-19 Are Robust Against Variants
REASON #7: Coronaviruses Don't Mutate Quickly Like Influenza, Which Requires Annual Booster Shots

I could not agree more with her. We need to be thinking these issues through logically and without emotion. I will need to see robust safety data and a reason to boost before I will go down this road. So far, I have seen neither. This calculous may be different for those over 65 years of age and/or those with comorbid disease. That is the group having breakthrough cases resulting in rare hospitalizations and even more rare deaths. We also have to keep the rational perspective that once you have had natural disease or death, the negative outcome curve plummets back to earth. Perspective is key when making any decisions. For more on the science of immunity over time, reread #43 or listen to the audiocast on iPodcasts.

8) From the UK, a study notes that if you were vaccinated against SARS2 versus not, you will have decreased long term (>28 days) symptoms if you subsequently acquire natural infection. (Antonelli et. al. 2021) This is the first study that I have seen showing a differential response between immunized and those not immunized against SARS2 with regard to long term symptoms post infection. The remainder of the analysis reinforced many other studies showing significantly reduced all cause issues related to being in the vaccinated cohort.

9) The effectiveness of masks has been looked at again. This time in a very interesting village study in Bangladesh in an unvaccinated population. They found that there was an 11% risk reduction in contracting and or spreading SARS2 (Peeples L. 2021) This is a modest risk reduction at best, but it is still a reduction.

If we layer different levels of protection, risk will reduce even further. Masks, vaccines, immune solvent lifestyle choices like healthy nutrition, adequate sleep and moderate exercise all stack up to benefit the average person.

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,

Dr. M

Leonhardt NYT
Scheepers MedRxIV
Gazit MedRxIV
McDade Nature
Egbert JAMANetwork
Allen NYTimes
Antonelli Lancet Infectious Diseases
Peeples Nature
Joseph STAT
CDC Variants Page


The Federation of State Medical Boards (FSMB), which supports its member state medical licensing boards, has recently issued a statement saying that providing misinformation about the COVID-19 vaccine contradicts physicians’ ethical and professional responsibilities, and therefore may subject a physician to disciplinary actions, including suspension or revocation of their medical license. We at the American Board of Family Medicine (ABFM), the American Board of Internal Medicine (ABIM), and the American Board of Pediatrics (ABP) support FSMB’s position. We also want all physicians certified by our Boards to know that such unethical or unprofessional conduct may prompt their respective Board to take action that could put their certification at risk.

Expertise matters, and board-certified physicians have demonstrated that they have stayed current in their field. Spreading misinformation or falsehoods to the public during a time of a public health emergency goes against everything our Boards and our community of board-certified physicians stand for. The evidence that we have safe, effective and widely available vaccines against COVID-19 is overwhelming. We are particularly concerned about physicians who use their authority to denigrate vaccination at a time when vaccines continue to demonstrate excellent effectiveness against severe illness, hospitalization and death.

We all look to board-certified physicians to provide outstanding care and guidance; providing misinformation about a lethal disease is unethical, unprofessional and dangerous. In times of medical emergency, the community of expert physicians committed to science and evidence collectively shares a responsibility for giving the public the most accurate and timely health information available, so they can make decisions that work best for themselves and their families.

Warren Newton, MD, MPH
President and CEO
American Board of Family Medicine

Richard J. Baron, MD
President and CEO
American Board of Internal Medicine

David G. Nichols, MD, MBA
President and CEO
American Board of Pediatrics