For some, now may be the time to get your third Covid shot

post by Josh Jacobson (joshjacobson) · 2021-07-10T17:38:57.686Z · LW · GW · 8 comments

Contents

  Summary
  Bullets
None
8 comments

Summary

Bullets

  1. 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.

  2. Today, Pfizer put out a statement which included the following:

    Pfizer and BioNTech have seen encouraging data in the ongoing booster trial of a third dose of the current BNT162b2 vaccine. Initial data from the study demonstrate that a booster dose given 6 months after the second dose has a consistent tolerability profile while eliciting high neutralization titers against the wild type and the Beta variant, which are 5 to 10 times higher than after two primary doses. The companies expect to publish more definitive data soon as well as in a peer-reviewed journal and plan to submit the data to the FDA, EMA and other regulatory authorities in the coming weeks. In addition, data from a recent Nature paper demonstrate that immune sera obtained shortly after dose 2 of the primary two dose series of BNT162b2 have strong neutralization titers against the Delta variant (B.1.617.2 lineage) in laboratory tests. The companies anticipate that a third dose will boost those antibody titers even higher, similar to how the third dose performs for the Beta variant (B.1.351). While Pfizer and BioNTech believe a third dose of BNT162b2 has the potential to preserve the highest levels of protective efficacy against all currently known variants including Delta, the companies are remaining vigilant and are developing an updated version of the Pfizer-BioNTech COVID-19 vaccine that targets the full spike protein of the Delta variant.

CNN says they plan to submit to the CDC for emergency approval to administer booster doses next month.[1]

  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.

  2. 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.

  3. 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.

  4. There are various reasons why getting vaccinated now may be particularly good for you

    1. Symptomatic infection may be bad to you, especially if you or someone you interact closely with is particularly vulnerable.
    2. If you received your vaccine early (e.g. 2020-February 2021) your protection is more likely to have weakened.
    3. Your peak exposure may be soon if the Delta variant has a similar effect in the US as it did in the UK. You’d also need to plan for the 1-2 week delay between shot and effect.
    4. When a booster shot likely does get approved by the CDC in ~1-3 months, there may be a run on supply preventing getting a vaccine booster for some time.
  5. There are also various reasons to not pursue a booster vaccine now

    1. You may care primarily about protection against severe disease, which seems to largely be maintained in the face of the Delta variant.
      1. You may be in good health / young, in which case you have additional reason to believe you will be fine even if you contract Covid.
    2. If less time has passed (under 4-5 months?) since you were vaccinated, then your potential benefit is likely less than some bullets above probably suggested it was for those who have had more time pass.
    3. Some, such as the CDC and FDA, don’t think a booster is currently warranted.
    4. It’s unclear to me if it’s legal to get a third dose in the US prior to that being approved. Regardless, it may be hard to procure without misrepresentation of your previous vaccinations.
    5. More data on safety, optimal timing, etc. will be forthcoming and may help you make a better decision.
    6. Boosters may be available this fall that specifically target newer variants, and perhaps getting a booster now will in some way make procurement of those worse (worse side effects, mandatory wait time since last vaccine, etc).
    7. Getting an additional dose of vaccine may ‘take it away’ from somebody else who needs it more, due to global supply limitations.
    8. You may believe the Delta variant is unlikely to lead to a large wave in your area, e.g. because of local vaccination rates or the ‘control system’.

For some, now may be the time to get your third Covid shot.


  1. Summary article of these developments. ↩︎

  2. For this reason, if pursuing a third booster shot soon, I’d lean Pfizer (smaller dose size) over Moderna. ↩︎

8 comments

Comments sorted by top scores.

comment by Josh Jacobson (joshjacobson) · 2021-07-26T22:14:25.249Z · LW(p) · GW(p)

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 [LW(p) · GW(p)]

comment by Ethan Perez (ethan-perez) · 2021-07-24T23:40:20.320Z · LW(p) · GW(p)

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.

Replies from: joshjacobson
comment by Josh Jacobson (joshjacobson) · 2021-07-25T02:08:09.839Z · LW(p) · GW(p)

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:

  1. 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.

  2. 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.

  3. 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.

Replies from: ethan-perez, ethan-perez
comment by Ethan Perez (ethan-perez) · 2021-07-25T19:26:27.741Z · LW(p) · GW(p)

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

comment by Ethan Perez (ethan-perez) · 2021-07-25T19:15:54.976Z · LW(p) · GW(p)

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.

comment by ofer · 2021-07-11T05:25:12.098Z · LW(p) · GW(p)

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.]

Replies from: joshjacobson
comment by Josh Jacobson (joshjacobson) · 2021-07-11T16:33:30.206Z · LW(p) · GW(p)

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!

Replies from: ofer
comment by ofer · 2021-07-12T19:43:26.914Z · LW(p) · GW(p)

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]?