COVID Transmissions for 3-31-2022
Fourth doses approved in the US; why we get influenza vaccinations every year
Greetings from an undisclosed location in my apartment. Welcome to COVID Transmissions.
It has been 835 days since the first documented human case of COVID-19. In 835, Ragnar Lodbrok, a semi-legendary Norse king, rose to power. Ragnar and his Viking forces cause quite a lot of trouble in France and England and affect the course of European history. Also, he has a bunch of kids with amazing names, like “Ivar the Boneless” and “Bjorn Ironside.”
Today in COVID-19 we’ll discuss the recent approval of fourth mRNA vaccine doses in the US. In the paid “Other Viruses” section I’ll talk about why we need annual vaccinations against seasonal influenza viruses, a somewhat similar situation to what we’re seeing with the evolution of SARS-CoV-2.
Have a great weekend!
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Now, let’s talk COVID.
Fourth dose approval
Here in the US, the FDA has authorized a fourth dose (or, a “second booster”) of the Pfizer or Moderna COVID-19 vaccines in adults age 50 and older, and quickly after this authorization, the CDC endorsed the provision of these booster doses.
I’ve mentioned this before, but vaccination schedule decisions in the US are not like other medications’ approval processes. For most medications, FDA approval is the major government endorsement hurdle. After that, market availability is restricted by a network of different private and public entities that pay for medications. The public entities, generally, are not allowed to negotiate pricing—by law. The private entities can. What the decision-making comes down to is generally the cost of the medication to the payor’s patient community, per whatever measure of benefit that the medication is expected to provide. That isn’t what we’re here to talk about today.
For vaccines, there are two government entities involved. The FDA approves (or authorizes, in the case of EUAs) a vaccine, and then, as in most countries that aren’t the US, a government committee (at the CDC) decides whether it is appropriate for the vaccine to be used on the public. This arrangement works particularly well for vaccines, because they are really inexpensive compared to other medications. If the CDC’s committee—ACIP—endorses the use of a vaccine, insurance companies are generally obliged to pay for it.
The decisions made at the FDA and CDC, for this reason, carry a lot of weight for vaccines. And so they are generally based on a lot of consideration and evidence, and involve the consultation of external experts serving on the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) and the CDC’s ACIP (American Committee on Immunization Practices), previously mentioned.
The decision made this week on additional COVID-19 vaccine boosters did not involve the consultation of either VRBPAC or ACIP. They were made directly by the CDC and FDA. This in itself is highly unusual, but I will note that it is entirely within the power of either agency not to consult its external advisors. Generally when they skip public advisory conversations, it is because they have decided not to let a product go forward onto the market. Here, it’s the opposite, which is strange.
What’s more, there is no package of public data that they seem to have drawn on in order to make this decision. While I cannot rule out the idea that perhaps Pfizer and Moderna supplied data privately that could not be made public for some reason, this is pretty irregular in itself. Medical regulation thrives on transparency and the provision of data that can be scrutinized at the very least by the healthcare professional public, if not the general public at large. Here, we don’t have that.
The only data on these additional doses that I have heard of comes out of Israel. The study, which has not been peer-reviewed, was not randomized and compared people who sought out a 2nd booster to people who had not. It demonstrated substantial prevention of death relative to the unboosted controls, but you have to ask yourself if that is really due to the vaccine, or due to the selected population. Are people who voluntarily get a booster likely to be those who are particularly cautious about COVID-19? Are they healthy enough to be unconcerned about adverse effects? Potential biases abound in a nonrandomized study of something that was not being actively recommended at the time.
So, I think I can summarize this by saying that I don’t see the evidentiary support for the decision that the FDA and CDC made here. This does not mean they are wrong; it just means that I don’t know they are right.
From a theoretical standpoint, they could very well be right. Evidence tells us that there is a population of neutralizing antibodies against the now-predominant Omicron variant, and these are enhanced by a booster dose—but they are transient, and they reduce in abundance over time. Add another dose, and you would expect to see these rise back up.
Except this invites another question—are neutralizing antibodies the entire story of immunity to COVID-19? We know they are a loose correlate of protection against symptomatic disease, but since protection against symptomatic disease is the least durable protection we can accomplish, is that what we really should be focusing on?
Let’s start from a premise that SARS-CoV-2 can’t be eradicated. Under that premise, what do we want a vaccine to do, really? Surely we do not expect a single vaccine to completely eliminate all risk of getting upper respiratory infections. Realistically, we should instead aim for something that can prevent all outcomes that lead to long-term harm to the affected patient. That means hospitalization and death, but it also means a reduction in long-term injuries due to the disease—things that largely fall under the label of “Long COVID” in popular discourse.
Preventing these kinds of outcomes, which vaccines appear to do quite well, I believe to depend upon the totality of the immune response. Yes, neutralizing antibodies probably contribute, but I also believe non-neutralizing antibodies, T cells, and other aspects of the immune response are involved in these protections. The totality of the immune response, and the protections that it provides, do not seem to have degraded much even in the face of Omicron variant emergence.
All of this having been said, there are cases where I unequivocally support a “4th dose,” or a “2nd booster.” These cases are ones where patients are at serious risk due to comorbidities that interfere with immune function or otherwise vastly increase risk of serious negative outcomes. People in this category need to be protected in a society that is increasingly rolling back other protections, and vaccines have to be a part of that.
And if I believe that the additional dose can work in that population, you can imagine that I am not too far from believing that it can help in other at-risk populations. Or even in every adult. But being “not far” from belief vs. believing in something are different things, and what it would take to push me over that line is compelling data.
However, let me put one key message alongside all of this: I also don’t think that this additional booster dose comes with any serious safety concerns in most people who did not already have serious safety concerns for their other doses of the vaccines. Those who have had three doses already are not likely to be at huge risk from this next dose, and if it can offer even some additional protection, it may well be worth the discomfort of a needle.
Do not take my questioning of this particular recommendation out of CDC and FDA as a statement that I don’t think additional boosters can do anything, or that they don’t work. This is a call for underlying data that support the decision, nothing more and nothing less. Regulation of medical products in the US relies on clear evidence-based justification, and I want to see that tradition respected here as well.
At the same time, I want to see everyone who reads my newsletter optimally protected from COVID-19. If your physician or other healthcare provider advises you to get that 4th dose, listen to them. They know you and your health better than I do.
Part of science is identifying and correcting errors. If you find a mistake, please tell me about it.
Though I can’t correct the emailed version after it has been sent, I do update the online post of the newsletter every time a mistake is brought to my attention.
No corrections since last issue.
What am I doing to cope with the pandemic? This:
Watching: The Last Kingdom
As a person who studied medieval history in college, I’m into stories that try to depict the lives of medieval people. Speaking of, the show Vikings actually follows and fictionalizes—even more than Norse sagas do—the story of Ragnar Lodbrok and his descendants, and was also an interesting watch.
Another show I’m into is The Last Kingdom, which follows a fictional warleader named Uhtred of Bebbanburg during the wars between the surviving kingdom of Wessex in what would become England and Danish (aka Viking) groups that invaded or settled Britain in the medieval period. If you’ve heard of King Alfred the Great, he was ruler of Wessex in a time when it came under particularly intense pressure—and he features prominently in The Last Kingdom.
Something I like about the show is that it demonstrates clearly the particular difference in life that a person could get from simply having a very good sword in their possession. Uhtred gets a very high quality sword at the start of the series, and by virtue of the fact that he has an excellent weapon and knows how to use it, he can turn himself into a valuable asset to powerful people—and inspire others to follow him. This is very true to the reality of the time as we understand it.
I’m watching the show again now because a new season has debuted. It has gotten a little soap opera-y, but I still like it and think it shows a version of medieval life that is different from the overwrought castles-and-knights stories that are common in older media.
We’re near the email length limit, so no comment review today. Check out the comment thread on the last issue for conversations about fish skin as well as about the naming of the gene called “sonic hedgehog.”
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For those who won’t be continuing beyond that into the rest of the paywalled section below—as well as everyone who will—please know that I deeply appreciate having you as readers, and I’m very glad we’re on this journey together.
Always,
JS
Why—and how—does the influenza virus vaccine change every year?
Since boosters are in the news for COVID-19 vaccines, I want to turn everyone’s attention to another area of vaccination where people routinely get a new vaccine dose: influenza prevention.
Influenza is a nasty disease that not enough people take seriously. It kills more than 200,000 people globally every year. It most severely affects older people, children, and pregnant women—generally speaking. And it only spreads to those people who it kills because not enough people get vaccinated.