The FDA went ahead and did it, approving a fourth vaccine shot for those age 50 or older. This is a reference post for those wondering if it makes sense to get that second booster.
The FDA approved the second booster by bypassing some of the normal procedures. Usual never-amused suspects are not amused.
What do those meetings and ‘public discussions’ do?
- Get picky about lots of little details.
- List all the reasons not to do something.
- Voice objections for all to see.
- Show lots of concern over trivial risks.
The Official Public Health Position is that doing all this Enhances Trust In The Process.
They are incorrect. And here is where their idea of ‘trust’ has gotten us.
Are they working hard on earning our trust back? Not exactly.
Their ‘scientific rationale’ is exactly what you think it is.
None of that means the standard drug process is necessarily bad or worthless. The process is very good at sniffing out any little potentially wrong thing or reason not to do something, and hence good at avoiding false positives. Which is sometimes what you want.
If your goal is to do a cost-benefit analysis to decide what to do, then turning things over to people who think costs and benefits do not belong in the same magisterium, and allowing them to act Deeply Concerned about things, does not seem like The Way.
The process is hopelessly biased towards delay, inaction and risk aversion. It makes sense to bypass it.
Nor does it seem like The Way to get Enhanced Trust. Yes, a few people will say ‘look, you did not hold the Official Meetings’ but actual regular people do not care. If anything, those arguments are crowding out arguments regular people would care about more.
For those shouting from the rooftops that ‘they’ would have us take infinite boosters forever, this is vindication of a sort. Yet it remains not even approved for others, let alone required.
There are good arguments against the second booster. That is fine. We can let individuals make their own choices.
Review: Should You Get a First Booster?
My answer to this continues to be yes.
The original design of the vaccine, of two shots in rapid succession, makes sense if you are trying to quickly test and deploy a vaccine in the middle of a pandemic. Pfizer and Moderna absolutely did the right thing to test that protocol given the situation.
However, there is lots of evidence that spacing the two shots so close together hurts long term immunity. Many vaccines involve much longer times between shots. In the UK, there were debates worrying that some people might not understand the importance of waiting multiple months between shots one and two, because that would make the vaccine less effective. We really, really should have done First Doses First.
Tests reliably show the first booster getting antibody response to levels well above those from the first two shots.
While the full effect of the booster fades over time, there seems to be a persistent and substantial effect on one’s permanent level of immunity.
Thus, even if the short term side effects for you are relatively unpleasant and you are young and in good health, I would get the first booster shot.
If you know you have had Covid-19, that likely functions in many ways as if it were a booster, at which point boosting or not boosting would be a small mistake. I would still boost, and definitely still boost if I was at high risk, but it is no longer obvious.
Should You Get a Second Booster?
The more important question, of course, is: Should you get a second booster?
I want to emphasize that my current viewpoint is that both decisions here are at worst small mistakes.
If you do get a second booster, the costs are minimal, beyond the short term side effects of being knocked on your ass to some degree for 0-2 days. There is a small risk that you make your immune system slightly less flexible if things change, but that seems like a small downside as well.
If you do not get a second booster, you still have robust protection against Covid-19. For now risk is even lower because we are up against Omicron and case numbers are not so high. If there is a new more dangerous variant you can reconsider your decision.
Here is what Vincent Racaniello has to say when my father asked him about the second booster and the potential dangers of antigenic sin/seniority. He is a name-chair professor at CUMC and the first person ever to sequence an entire virus genome, as well as a family friend.
Hello Professor, good to hear from you. If you are not too afraid, we
should have lunch sometime. Teaching virology in person without masks!
Second vaccine booster for those over 50 – the science doesn’t support
it. Three doses is doing fine at controlling severe disease and
hospitalization. You will never prevent infection, unless you want to
boost every 6 months. I’m not getting a second booster.
Original antigenic sin – it’s a possibility of course but we won’t
know until we deploy a variant-specific vaccine. In my opinion we are
not going to do this. Omicron is the most diverged of the variants,
escapes neutralization by serum from twice-vaccinated people, yet
severe disease is still controlled by the vaccine. I don’t see a
variant specific vaccine unless severe disease/hospitalization begins
As you know, for influenza virus, once HAI titers go below a certain
level, we know that correlates with increased severe disease so we
change the vaccine. We have no correlation between antibodies and
severe disease for COVID. That’s because antibodies control infection,
while T cells control disease severity. And as you know, most of the T
cell epitopes are not changed in the variants like Omega.
It is my understanding that flu vaccines suck at inducing a good T
cell response, hence we depend on antibodies. Not the case for COVID.
The mRNA vaccines are great at inducing T cell responses.
He also had some harsh words about the Israeli data underlying the decision.
Here are the data in the Israel paper. If you think they mean anything
you’ve lost your mind. Plus they make no attempt to compare the two
populations with respect to co-morbidities. These data are
Among participants aged 60 to 69, death from Covid-19 occurred in 5 of
111,776 participants in the second-booster group and 32 of 123,786
participants in the rst-booster group (adjusted hazard ratio, 0.16;
95% CI, 0.06 to 0.41; P<0.001) (Table S2).
Among participants aged 70 to 79, death from Covid-19 occurred in 22
of 134,656 participants in the second-booster group and 51 of 74,717
participants in the rst-booster group (adjusted hazard ratio, 0.28;
95% CI, 0.17 to 0.46; P<0.001) (Table S3).
Among participants aged 80 to 100, death from Covid-19 occurred in 65
of 82,165 participants in the second-booster group and 149 of 36,365
participants in the rst-booster group (adjusted hazard ratio, 0.20;
95% CI, 0.15 to 0.27; P<0.001) (Table S4).
Really, 5 vs 32, 22 vs 51, 65 vs 149 and you are making policy for the
US based on this? This is insanity.
Those sample sizes certainly seem small, but I do not know what the alternative is when a decision has to be made. I do think they mean something, but I agree they do not mean all that much, and in the longer term they mean essentially nothing. Part of what they mean is that risk even for the group over the age of 80 was not so high, and for other groups it was much lower.
Andy Slavitt, former senior Biden White House advisor, comes out in favor of re-boosting (Twitter thread). Main arguments are potential reductions in Long Covid and in infecting others, and in getting back to ‘previous levels of protection’ in a future wave. No numbers that support getting re-boosted are cited, and I find the case here unconvincing.
I am not as down on the second booster or its supporting data as Racaniello is above. I also do not agree with the principle that we should wait for proof before allowing people to take potentially life-saving medicine, especially once safety has been established.
My guess is that if you take a second booster, the following things happen.
- You will have short term side effects similar to your first booster.
- For the next four to six months, you are more protected from Covid-19.
- This includes less infections, and less infecting others, less Long Covid.
- But from a baseline with robust protection versus hospitalization and death.
- Then the benefits will fade unless you boost again.
- No meaningful longer term impact, if anything tiny negative.
And that’s it.
Is it Worth It?
That depends on several factors.
- Severity of your side effects from the first booster.
- How old or unhealthy you are.
- Expected amount of Covid-19 in your area.
- Whether you already had Covid-19 especially recently.
- Whether there is a new variant worth worrying about.
- Whether we know the old vaccine works on that new variant.
My answer, for me, is no, I am not interested. The third shot was not too bad, but the next day was not especially fun, and I see little benefit. I do not intend to voluntarily get a fourth shot even if allowed and encouraged, unless we are facing:
- A new wave.
- From a new variant.
- Where the old vaccine works.
- But severity is higher.
That is also because I am young and healthy, so much so that I am not even currently eligible. If I was sufficiently old and/or unhealthy, I would have a lower threshold for boosting, but I would still wait until conditions were getting worse to better time the benefits.
Timing is Everything
Several times, I have heard people say that ‘trying to time the booster is like trying to time the stock market.’
And no, trying to time the booster is not at all like trying to time the stock market.
Trying to time the booster is more like trying to time buying a winter coat.
Stock market prices are anti-inductive. You can only time the market by outsmarting the market. Which is hard.
If there was a prediction market on future case numbers, and the only way to time your booster was to time that prediction market and make a good trade, that would also be hard.
You don’t have to do that. All you have to do is wait until cases are high and rising, and then get your booster. It takes a week to work. Noticing a wave at least a week before it gets bad, or at least a week before most of the cumulative danger you will face, is very easy.
The sense in which you have to ‘beat the market’ is the danger that everyone might be trying to get the booster at the same time when things are about to get bad, and fighting for limited appointment slots. That is potentially a concern, but given people’s reluctance to boost, I do not anticipate there being enough additional demand to cause much of an issue. Even if there is, you’ll have ample warning.
- Cost of second booster is small.
- Benefit of second booster is small and temporary.
- If you’re at very high risk, maybe it makes sense.
- Either decision is at worst a small mistake.
I guess it’s not surprising at all at this point that credentialed medial people can have terrible takes, The idea that the data are meaningless is absurd. P<.001 3 times (on the obvious non-contrived endpoint) is P<.001 3 times. He says they don't control for comorbidities, but table 2 in https://www.researchsquare.com/article/rs-1478439/v1 shows that they considered it, and the older+sicker=more second boosters that they found only makes the death reduction more robust. Maybe they haven't shown some Officially Recognized Statistical Method Results (yet?), but that's FDA-esque whining, not an honest truth-seeking evaluation. This paper is strong evidence that the (short-term) COVID-benefit of a second booster is real.
The benefit is small enough (because the overall risk is low enough that cutting it by 80% or whatever is still small) that there are questions around whether paying for it is worthwhile, or if it outweighs whatever rare vaccine side effects or a day of feeling like crap for people who felt like crap after earlier doses. That's all reasonable and valid. Disagreeing with a policy prescription and reflexively dismissing clear evidence in favor of it, not so much.
Anti Inductive link is broken
I’ve seen a hypothesis advanced by Brett Weinstein (origin of the hypothesis offered in good faith given the current political climate, but obligatory reminders that an idea should be judged on its merits, not its proponents, etc., etc.) on the mechanism that could explain why myocarditis or other heart disease were among the most severe the side-effects linked to the mRNA vaccines. Given my current level of expertise, I do not trust my judgment to reject or validate this claim. Therefore, I’d like to ask what probability of truth I should assign to it in this place. To be noted I am posting and assigning probabilities before doing my own research since I do not trust myself to correctly discriminate sources of information on this subject.
The hypothesis rests on two claims:
1 – Heart tissue cells have much lower, i.e. little to no, capacity to duplicate and subsequently repair damage induced from an external source than cells from other organ tissues, and instead repair such damage using scars instead -> I give this a 90% probability: BW is a biologist and should know his stuff on such a subject and this should be known data in biology. However, it seems inherently strange to me, even given the evolutionary advantage of therefore limiting tumors in the heart.
2 – There is a possibility that the immune system would flag cells “infected” by the mRNA vaccine as cells infected by a virus and therefore would seek to destroy them. -> 50-60% probability here. this makes intuitive sense given the fact that the method of action of the mRNA vaccine IS identical in many ways, technically, to a virus, albeit one we engineered to be beneficial to us. However, this has not been tested, AFAIK, and it seems weird that such an obvious secondary effect of this technology would not have been anticipated. BW’s idea here is that this is a known effect, and is supposed to be mitigated by engineering the vaccine to remain fixed near the point of injection, which did not work in this case.
If both are the case, then the mRNA vaccine would result in most cells affected by it being destroyed, but with the most obvious lasting damage being visible in heart tissue
Given these claims, what truth probability would you assign each of them?to the full hypothesis? Have you heard it anywhere else and is there any investigation being performed to validate or invalidate it, or has such work already taken place? Would results stemming from such experiments be worth taking into account in the decision to boost or to vaccinate?
video link for more complete explanation: https://www.youtube.com/watch?v=9Ej6PIVnHeQ
Today I put up some thoughts about second boosters.
It took me a couple days, because I looked through:
– the FDA/CDC releases themselves as primary sources,
– some of the more reasonable news outlets like STAT News
– then I thought over the advice you got from Racaniello (ended up disagreeing because the results are statistically significant and a strong effect size as seen in the hazard ratio; ended up agreeing that the groups were confounded with the “volunteer” effect and applied to an already-low risk),
– read through the 3 Israeli studies (at least looking through all the figures and tables,
and reading the conclusions),
– had a look at some studies of boosters vs Delta and Omicron from the UK Healty Security Agency,
– and finally consulted Eric Topol and Katelyn Jetelina (aka Your Local
Epidemiologist) in some longer-form essays on their blogs.
My conclusion is broadly similar to yours, although we do disagree on a few points.
My actions, however, were different — I just got the booster an hour and a half ago — because I’m
in an older age group, doubt my ability to forecast a wave to get out ahead of others
vying for scarce vaccination slots, and see the Omicron/BA.2 wave in Europe as an ominous
short-term portent. And I’m a little more COVID risk-averse.
I followed the advice from Topol (via the Kaplonke paper in Science) and got
Moderna on top of Pfizer to increase ab diversity and T-cell response diversity.
I expect to feel crappy this weekend. And I’m totally ok with that.
You say impact of second booster: “No meaningful longer term impact, if anything tiny negative.”
Could you explain what negative impact could result?
Original antigenic sin/seniority, making it more difficult to adapt to new variants, is possible.
Vaccine passports becoming dependent on continued boosting, as some anti-vaccine passport people correctly predicted.
Nothing else need to be said.
(I’ll take it as far as I need to use the vaccine passport, which might be the case in HK – not in the mood of boycotting anything the business owners aren’t responsible)
Cool that you know Dr Racanniello, and not unnoticed you spent some time addressing the OAS question. I’ll stop bugging you about booster necessity, and I better appreciate now the importance of them especially in the context of the initial 2 dose spacing being so close in the US and Israel, irrespective of age.