Thread by @celinegounder

1/ New Israeli PRE-PRINT on the impact of Pfizer vaccine boosters:
medrxiv.org/content/10.110…

On 7/30, Israel started giving Pfizer booster doses to those 60+.

They then expanded Pfizer boosters to younger age groups:
50-59 on 8/13
40-49 on 8/20
30-39 on 8/24
16+ on 8/29

2/ It's interesting to note who got boosters and who didn't.

People who got boosters were more likely to be:
- Male
- general Jewish (vs Arab or ultra-Orthodox Jewish)
- Age 70+

3/ It takes time for the immune system to respond to vaccination.

People also behave differently immediately after vaccination than they do a couple weeks later.

So let's focus on the impact of a booster 12+ days after a booster dose.

4/ The rate of COVID DEATH was TOO LOW among people UNDER 60 (boosted or not) to allow for meaningful comparison.

Among those 60+,
12+ days after a booster dose,
there was a ~15x reduced risk of death
out to 2 months vs unboosted.

Supports giving people 60+ a booster dose.

5/ The rate of SEVERE COVID DISEASE was TOO LOW among people UNDER 40 (boosted or not) to allow for meaningful comparison.

Among those 60+,
12+ days after a booster dose,
there was a ~19x reduced risk of severe disease
out to 2 months vs unboosted.

6/ This also supports giving people 60+ a booster dose.

7/ The rate of SEVERE COVID DISEASE was TOO LOW among people UNDER 40 (boosted or not) to allow for meaningful comparison.

Among those 40-59,
12+ days after a booster dose,
there was a ~22x reduced risk of severe disease
out to 2 months vs unboosted.

8/ This supports giving people 40-59 a booster dose.

9/ HOWEVER, note that they only followed people out to 2 months after booster dose.

It's unclear whether the impact on protection vs death was due to transiently boosted antibody levels (THEY WILL GO DOWN) or improved immune memory responses.

10/ If the impact on severe disease and death risk is due to:
- transiently boosted antibody levels, bump in protection from booster will be transient.
- improved immune memory responses, the bump in protection from booster will be longer lived.

11/ They didn't look at the impact of boosters on the risk of severe disease and death from COVID among people under 40 because the risk was so low whether or not they got a booster dose.

12/ Now let's look at the rate of INFECTION among those who got a booster or didn't by age:

Among those 50+,
12+ days after a booster dose,
there was a ~12x reduced risk of infection
out to 2 months vs unboosted.

13/

Among those 40-49,
12+ days after a booster dose,
there was a ~10x reduced risk of infection
out to 2 months vs unboosted.

14/

Among those 30-39,
12+ days after a booster dose,
there was a ~9x reduced risk of infection
out to 2 months vs unboosted.

15/

Among those 16-29,
12+ days after a booster dose,
there was a ~18x reduced risk of infection
out to 2 months vs unboosted.

16/ AGAIN, note that they only followed people out to 2 months after booster dose.

It's unclear whether the impact on protection vs infection was due to transiently boosted antibody levels (THEY WILL GO DOWN) or improved immune memory responses.

17/ If the impact on risk of infection is due to:
- transiently boosted antibody levels, bump in protection from booster will be transient.
- improved immune memory responses, the bump in protection from booster will be longer lived.

18/ So in summary, assuming other studies support these findings, this MIGHT support giving boosters to Pfizer vaccine recipients who are:
- 40+ years of age to prevent severe disease and death
- 16+ years of age to prevent infection

19/ I say *MIGHT* because:
- We don't know if the bump in protection is transient or long-lived. From a population-level perspective, it probably doesn't make sense to vaccinate 100s of millions of people for a short-term bump in protection.

20/
- You don't need to prevent all infections to reduce transmission.
- People with breakthrough infections after vaccination are at a lower risk of developing long COVID than are unvaccinated people who get infected.

21/ It will be really important to assess the impact of booster doses on:
- neutralizing antibody titers, memory B-cell, long-lived plasma cell, and T-cell responses over time
- protection against infection, severe disease, and death over time

2 months of follow-up isn't enough.