Hail to the Chief: DA Henderson's Mind was the Ultimate Pandemic Countermeasure

The infectious disease world has been without DA Henderson for exactly 5 years and his presence is something that is needed more than ever. i don’t think there’s every going to be a time when we don’t need his mind, his knowledge, his experience, and his wisdom.

Each year on the anniversary of his death I pose questions to him that I wish I could hear him answer. His booming voice, his certainty, his ability to see things exactly for what they were drawing on decades and decades of battling — and annihilating — humankind’s greatest scourges are a far cry from what we hear and see today. Given the current environment, I just wish he could take over the whole infectious disease apparatus and extinguish this pandemic, recalibrate public health, and silence politicians whose continual incompetence is to blame for over 600,000 lives.

Each day I have questions for DA and these are a selection of my latest ones.

1. How do you counsel the population about a new infectious disease that is going to become endemic? How do you dial down people’s sense of alarm to one in which they learn to risk calculate? You did this, I am sure, with the 1957 and 1968 influenza pandemics, Legionnaire’s Disease, HIV, and countless others.

2. This is a related question. How do you transition people away from an abstinence only message to one of harm reduction? This must have been something you thought about in the early days of the HIV pandemic. Harm reduction works but was jettisoned early on in the pandemic and stunted people’s ability to risk calculate — a skill they need to acquire immediately as COVID-19 is not going away

3. What is the value of chasing mild cases of COVID-19 in vaccinated individuals? How is there an end game if that becomes the goal? During H1N1 in 2009, I remember how quickly things changed when the severity was downgraded. Isn’t that what vaccination is doing to COVID.

4. This is less of a question but more of a request to be regaled with another of your innumberable stories bout how you put a politician, a president, a dignitary in their place when they were pursuing a policy you didn’t think highly of. These are my favorite WWDAD thought experiments. I am smiling thinking of the time the Secretary of HHS was waiting to speak at a conference and wanted to interrupt your talk and someone approached the podium the Secretary was there and you replied deadpan “I know” and continued your talk. We could use a lot more of that now.

5. What is going on with those melioidosis cases in 4 different states in which there is no travel history or linkage? Where do you think they came from? An imported product? A real mystery that is overshadowed by COVID

6. Is polio eradication in the new Afghanistan even possible? You were so skeptical it could be accomplished a decade ago and now the situation is way way worse. Should it be abandoned and just become part of regular disease control?

7. What do you think of the Ebola cases in the Ivory Coast? It’s the Zaire strain again not the Cote d’Ivoire or another strain. How do the different strains circulate ? How does one spillover and another doesn’t

These are just the first 7 out of an endless list of questions I have for DA. Tomorrow there’ll be a slew more new ones that occur to me.

One of the aspects of DA that is impossible for me to fully articulate is the feeling I got being around a mind like his. It was a feeling that allowed me to think that insoluble problems were soluble and that a human mind could tame the most wickedly virulent microorganisms.

If those of us that had the opportunity to work alongside him and be mentored by him could pool just a fraction of what he imparted to us, the world would look a lot different now. Emerging infectious diseases would be running scared with just a hint of our commander-in-chief.

Thoughts About Immunity and Booster COVID-19 Vaccine Doses

The recent announcement by the Biden Administration that fully COVID-19 vaccinated adults would be offered booster vaccine doses 8 months after their 2nd dose prompted a lot of thinking and my doing a lot of explaining about immunity and vaccines. 

I wanted to think a little on paper to try to explain what immunity means, what to expect from a vaccine, and draw some conclusions regarding the impending booster program.

So, what is important about COVID-19 vaccines? Their most important aspect is their ability to prevent severe disease, hospitalization, and death. That is what they were designed to do, and they are doing it brilliantly with a combination of antibodies and T-cells. Indeed, the FDA authorization was based on the ability of the vaccines to stop disease (i.e. symptoms) not clinically silent infections. Hospitalized COVID patients are, for the most part, not vaccinated. There has not been waning of the ability of vaccines to prevent these outcomes (though the White House said it “could”) despite crude Israeli data that cannot be taken as evidence given the statistical paradox present. 

The human system is very complex and hard to simply describe. We have innate (or ready-to-go non-specific immunity) and a more targeted specific type of immunity that takes time to develop called adaptive immunity. Adaptive immunity “adapts” or is directed towards specific pathogens. In broad strokes, there are two aspects to adaptive immunity: humoral (or antibody) mediated immunity and cell-mediated immunity. Both are very critical and work in concert. A major component of cell-mediated immunity are T-cells. There are various types of T-cells including T-cells that can kill infected cells, T-cells that orchestrate the operation of the immune system, and T-cells that dampen inflammation. 

 The most common evidence cited for the need for boosters is waning antibody levels. However, this is not – in and of itself – enough. First, we do not know what level of antibody (and the rarely accounted for T-cell immunity) is needed for immunity. We also do not have clinical evidence of true vaccine failure against important outcomes like hospitalization. There is non-peer reviewed data from Moderna showing higher efficacy with higher antibody titers but importantly, as the paper states, it is limited by the fact that efficacy against severe COVID was not assessed.

 It is well known that antibody levels fall and then spring back up post-exposure (to the virus or the vaccine). That is how the immune system works – it is anamnestic. It “remembers” after the primary response and mounts a heightened response that staves off severe illness using both T-cells and antibodies in the secondary response. We fully expect antibodies to fall as time from exposure to vaccine or infection increases and we fully expect them to rise upon re-exposure. This isn’t vaccine failure; it’s just how the immune system works. That, infections in the vaccinated are generally mild is evidence of this process working.

When the CDC recommended a modification of the primary immunization series for the immunocompromised – which is distinct from a booster – it did so based on clinical evidence that amongst the relatively rare COVID hospitalizations of vaccinated individuals, the immunocompromised were overrepresented (~45% in a non-peer reviewed paper). Additionally, a study in solid organ transplant patientsrevealed not only did they, as expected based on experience with other vaccines, fail to mount a robust (or sometimes any) antibody response but had a 485X increased chance of COVID hospitalization versus someone without a transplant. That type of clinical evidence was then integrated with data on 3rd doses of mRNA vaccines increasing antibody levels in these populations. 

With this booster recommendation to the public, none of that type of clinical data appears to be available for analysis. It is even unclear 

Vaccines are not bug zappers; they are not forcefields. That breakthrough – the term itself falsely connotes vaccine failure – infections are mild is a vaccine success (even as they may increase in frequency). We must remember it is disease not clinically irrelevant infections we are targeting and that is done with 1st and 2nddoses, not 3rd’s. COVID is an endemic respiratory virus, it cannot be eliminated or eradicated. There is marginal utility in the general healthy population getting booster vaccinations at an 8-month interval. It is currently unclear that a 3rd dose will diminish the rare transmission risk posed by the fully vaccinated which prompted CDC guidance on masks to be modified. Granted, there is little harm but is chasing mild infections in the fully vaccinated an important task when a substantial proportion of the eligible population of this country does not even have one dose. Will this change the trajectory of the pandemic in the US or the world? Does putting 3rd doses in the arms of the heavily vaccinated change the situation in Mississippi? 

There may come a time when boosters are needed and it’s important to be proactive and have streamlined approval and distribution pathways, but I don’t think that time is 8 months.