Written by JobSiteCare
August 19, 2021
This week, the big development has to do with boosters for Covid 19 vaccinations. There have been lots of recommendations floating around including leaks of a major new recommendation to be made from the White House tomorrow. We will work through what we know of these recommendations and what data there is to support them.
Last week, the FDA authorized what is technically not a booster, but guidance that primary immunization for people who are immunocompromised should consist of 3 shots. This is based on fairly clear studies that these people never mount full immunity with two shots. But, with a third dose, their immunity is often brought up to a level on par with the general population. The full list of categories for whom this three-shot primary series is recommended is widely published, so it will not be included here, but importantly, it does not include people who are relatively immune-compromised by age, alone. People who are on significant steroid doses or other immunocompromising medications are included, but this will be a small subset of the population. The studies supporting the need for a third shot in this narrow population are very good both from a lab-based analysis of antibody levels as well as from experience data regarding infection rates. So, this part is straightforward.
Now the less straightforward issue:
Pre-announcement releases indicate that tomorrow, the White House will announce that the CDC will authorize and recommend a third dose of mRNA vaccine for those who have been considered “fully vaccinated” for 8 months. This truly would be a booster dose, based on data that there is a drop in antibodies that is fairly steady through about 6-8 months. The curve then flattens and while there is still some continued decrease, adequate immunity is generally still present for a prolonged period, probably measured in years. Unpacking that last sentence, the keyword here is “generally.” Saying that most people are adequately immune for a prolonged period means that not everyone is, and since there is no good way to predict who does retain immunity and who does not, the guidance will be to add a third dose to get most everyone into the level of prolonged adequate immunity. We do know that people who are older have a higher likelihood of dropping their immunity, but it appears the recommendation will be structured so that a third shot will be authorized 8 months after completing the first two. By the nature of the initial rollout of the vaccines, people at higher risk will be at the front of the line for the third shot, so it is unclear that age requirements will be applied, although that is still under discussion.
Importantly, these third shots will not be authorized to begin until September 20th. Since vaccine programs did not really get rolling until January and the 8-month clock starts from the second dose, this means that there should not be a crush of demand right away, especially considering that the overall demand for vaccinations is relatively low right now. The initial word from the White House is that obtaining the third shot will be based simply on showing your current white vaccination card with a date of second shot that is at least 8 months prior to the current date.
A couple of key points:
- This third shot has not yet been authorized by the US Food and Drug Administration. Typically, the FDA authorization precedes the announcement of a vaccine program by the White House, so the Administration is not seen as putting politics ahead of dispassionate scientific rigor, but likely because of the confusion provoked by the current third shot recommendations for those who immunocompromised.
- As you may have noticed, we have only been referring to third shots, so that addresses only the Pfizer and Moderna vaccines in the United States. Various sources have indicated that Johnson & Johnson vaccine will likely be included in booster recommendations, but with the safety issues that arose with the Johnson & Johnson vaccine regarding blood clots primarily in women of childbearing age, the White House does not appear to want to make an announcement before further scientific evaluation.
- This is all based on findings regarding decreased antibody levels over time. As we have discussed in prior updates, antibody levels are just one part of the immune system and reasonable evidence has been developed that cellular immunity, as opposed to antibody-based humoral immunity, is durable. Still, findings from Israel have shown that cases, especially due to delta, do increase as people are further out from their initial vaccinations. But, the protection against severe disease is still very good, for most people. So, the decision to recommend this third shot is not completely supported by studies however, it’s not refuted either. More data is really needed to be sure.
So with all that, just because this may be authorized, should you get it?
As noted earlier, the data for clearly immunocompromised people is good, and it is reasonable to extrapolate that data to relatively immunocompromised or those who may be at greater risk. So, the older someone is, the more likely that this would be beneficial. For people with significant risk factors, such as obesity, chronic lung disease, or significant heart disease, the small risks associated with a third shot are likely less than the risks associated with contracting the disease. As we have seen, most of the bad outcomes amongst vaccinated people have been in those with other risk factors, so decreasing the risk of contracting the disease can have a meaningful effect on the risk of bad outcomes.
On the other hand, for people who are already at low risk of significant disease by virtue of being younger, healthier, and especially if vaccinated, the drop in risk may not be greater than the risk associated with (still admittedly low) risk associated with a third shot.
Fortunately, we have at least another month to analyze more data, and for the younger portion of the population, perhaps a few months, so most people do not need to decide today. We still found that the data supports a primary vaccination series, whether the one or two-shot series that most people have had or the three-shot series recommended for immunocompromised people. And, right now, we very much lean towards a booster for older people, but we still want to hold judgment until we see more data for everyone else.
Three last points for this week:
- Note that this booster recommendation is still using the original formulation. We know that all the major manufacturers are working on modifications that may more directly address the key variants, but there is little information on the timeline for these potentially modified vaccines. As we get closer to the September 20th start date for the booster program, I hope we have more information on these shots.
- The recommendations will specifically say you should be boosted with the same vaccine you got the first time. If you got an mRNA, it is permissible, but not recommended to get the other mRNA, but mixing in an adenovirus vaccine such as the Johnson & Johnson vaccine is not recommended. There are multiple very good studies that have demonstrated that getting a different technology vaccine as either a booster or as a second dose has significant benefits in terms of antibody response and without higher safety risks. These are primarily not US studies, so the US decision-makers are not incorporating these findings into their analysis for now. This is another reason why we are content to wait until the program starts to have more information.
- This booster concept is not without ethical concerns. There are still large populations who have not had access to vaccines. If developed nations take up available stock for a booster (not including the third shot for those who need it because they are immunocompromised), and by doing that reduce vaccine available to emerging markets, there are questions of the ethics of that as well as concerns about leaving unchecked the spread of the virus and thus increased chance development of variants.