They Don’t Know About Second Booster

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?

1. Delay.
2. Get picky about lots of little details.
3. List all the reasons not to do something.
4. Voice objections for all to see.
5. 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
to rise.

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
meaningless.

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.

1. You will have short term side effects similar to your first booster.
2. For the next four to six months, you are more protected from Covid-19.
3. This includes less infections, and less infecting others, less Long Covid.
4. But from a baseline with robust protection versus hospitalization and death.
5. Then the benefits will fade unless you boost again.
6. No meaningful longer term impact, if anything tiny negative.

And that’s it.

Is it Worth It?

That depends on several factors.

1. Severity of your side effects from the first booster.
2. How old or unhealthy you are.
3. Expected amount of Covid-19 in your area.
4. Whether you already had Covid-19 especially recently.
5. Whether there is a new variant worth worrying about.
6. 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:

1. A new wave.
2. From a new variant.
3. Where the old vaccine works.
4. 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.

Bottom Line

1. Cost of second booster is small.
2. Benefit of second booster is small and temporary.
3. If you’re at very high risk, maybe it makes sense.
4. Either decision is at worst a small mistake.