See responses to later bounty request on this topic as well, in particular the response linked: https://www.lesswrong.com/posts/fBGzge5i4hfbaQZWy/usd1000-bounty-how-effective-are-marginal-vaccine-doses?commentId=Rd3f3KiAMFNvpJAhu
How likely do you think it is that a third dose causes people to have too strong of an immune response to a real (breakthrough) COVID infection? I've heard that some past infections (e.g., dangerous kinds of flu) cause more deaths in young/healthy individuals than old individuals, when an immune over-reaction is the primary cause of severe illness.
I entertained a similar hypothesis, but I now feel comfortable not including that to a meaningful extent in my decision making.
There's some evidence against this that I consider significant:
I read ~3 doctors' takes on this question regarding a third dose; they all thought this sort of potential negative effect was very highly unlikely. At least one of them had a detailed explanation as to why that sounded reasonable to me (I'm not a medical professional), and that made that take a bit more additionally meaningful to me than those takes without explanation.
Anecdotally, I feel like I would have seen more indication that this is a concern in the clinical trials news or in the news regarding those who are receiving / have received third shots, if it were substantial.
The pattern that you refer to hearing about with dangerous kinds of flu has seemed to be the opposite of general covid severity and death patterns by expected immune response (age).
I don't have a particular likelihood to assign; this is the summary of the evidence I have.
Also, do you think such adverse effects would also be unlikely for a fourth dose? E.g., since third dosers will probably also want to take whatever delta booster comes out
Very helpful, thanks! That alleviates some of my concerns. Do you have any links to the doctors' takes on this question? I'd be interested to read more about what they said.
What you call a "significant indication that a third dose of an mRNA vaccine has a good safety profile" seems to be mostly just statements by vaccine manufacturers. Furthermore, in your list of 8 "reasons to not pursue a booster vaccine now" you don't directly mention anything about potential health risks from taking a booster shot (which I'm not aware of the FDA claiming to be safe).
[EDIT: I'm not saying here whether it's a good or bad idea for someone to get a booster shot. Also, statements by vaccine manufacturers can obviously be important evidence (in a Bayesian sense) for the safety profile, so the way I commented on the first quote may have been overly negative.]
What you call a "significant indication that a third dose of an mRNA vaccine has a good safety profile" seems to be mostly just statements by vaccine manufacturers. ... Also, statements by vaccine manufacturers can obviously be important evidence (in a Bayesian sense) for the safety profile
I agree that statements by Pfizer and Moderna are important evidence. Additionally, the Moderna report I linked included "The frequency of any Grade 3 solicited local or systemic adverse events was 15% after the third dose of mRNA-1273 and 10.5% after the third dose of mRNA-1273.351. There were no Grade 4 solicited local or systemic adverse events. The most common solicited local adverse event was injection site pain in both groups. The most common solicited systemic adverse events after the third dose of mRNA-1273.351 or mRNA-1273 were fatigue, headache, myalgia and arthralgia. In general, mRNA-1273.351 had a lower reactogenicity profile than mRNA-1273 in this study."
I agree with them that this indicates a similar safety profile to the first two doses, in which "15.7 percent experienced a severe “systemic” adverse reaction and 7 percent, a severe “local” reaction." https://www.vox.com/22158238/covid-19-vaccine-side-effects-explained
Perhaps I should have been more explicit about this evidence not having been reviewed yet by other parties.
Furthermore, in your list of 8 "reasons to not pursue a booster vaccine now" you don't directly mention anything about potential health risks from taking a booster shot (which I'm not aware of the FDA claiming to be safe).
In that list is:
Some, such as the CDC and FDA, don’t think a booster is currently warranted.
More data on safety, optimal timing, etc. will be forthcoming and may help you make a better decision.
Given the evidence for a good safety profile (which also does include evidence I didn't cite in my post), I personally think that this was an appropriate degree to which I indicated that safety wasn't as validated as it could be, although perhaps:
Some, such as the CDC and FDA, don’t think a booster is currently warranted.
would have been better as:
Some, such as the CDC and FDA, don’t think a booster is currently warranted; they also have not reviewed the safety of a booster dose.
Thanks for highlighting your concern!
To be clear, something can be 'substantial/important evidence' (in a Bayesian sense) even if it causes one to update their credence in something from 1% to 2%.
You mostly use the word 'indication' instead of evidence (e.g. "There is significant indication that a third dose of an mRNA vaccine has a good safety profile" and "I agree with them that this indicates a similar safety profile to the first two doses"). I'm not sure what you mean by that word in this context. Can you share with us your credence in the prediction that: [in 5 years it will be widely believed that such a booster shot (taken in July 2021) had a good safety profile] [such a booster shot having a good safety profile]?
Summary
Bullets
Two days ago, the Israeli government announced that its observed vaccine efficiency (Pfizer) as of June 6th was down to 64% against symptomatic infection, while protection against severe disease and hospitalization has declined more mildly to 93%. This is seemingly almost entirely attributed to the Delta variant.
Today, Pfizer put out a statement which included the following:
CNN says they plan to submit to the CDC for emergency approval to administer booster doses next month.[1]
Moderna previously announced that in their trial they also observed indication of significant benefit to a third dose booster (of half the size of the initial Moderna doses)[2] and found it to have a similar safety profile to the second shot.
In addition to the clinical trials, Turkey, the UAE, NYC, and some others have given people third doses in some circumstances / categories. The immunocompromised are particularly likely to benefit, as one would expect.
The Delta variant may have more of an impact than you expect. Polymarket currently gives a ~⅔ probability to the US again having more than 100,000 cases in a day before the end of the year. This could come from a new variant or other novel situation, but I expect most of this probability for most bettors is with an eye toward the Delta variant. Cases in the UK have increased 10-20x since their post-vaccination trough, and it has/had similar vaccination rates to the US (although less immunity from having contracted Covid, and a greater proportion with only one dose or a less effective vaccine). The UK’s current number of new cases is equivalent to ~160k new daily cases in the US when adjusted for population.
There are various reasons why getting vaccinated now may be particularly good for you
There are also various reasons to not pursue a booster vaccine now
For some, now may be the time to get your third Covid shot.
Summary article of these developments. ↩︎
For this reason, if pursuing a third booster shot soon, I’d lean Pfizer (smaller dose size) over Moderna. ↩︎