Boost or not: what does the data say?

September 4, 2022 By Alan Salzberg

Last week the CDC and FDA approved a new formulation of the Covid vaccine which includes specific targeting of the BA5 variant (see here).  This booster is bivalent, targeting both the original virus strain and the BA4/BA5 Omicron strain.  Sounds great, right?

Unfortunately, this booster was approved with no human data whatsoever on its effectiveness.  Moreover, even the animal data is crappy -- it includes results from just 8 mice (see a full Q&A on Science magazine's website here).   The mice were not even tested for protection against Covid -- instead, their antibody levels were measured.  While this is typical for updates and the flu vaccine, that vaccine, unlike the current Covid vaccine, is protective against infection (see Paul Offit's explanation here regarding why Covid vaccines do not protect against infection for current variants). In my mind, approving this booster based on no human data is an abdication of duty from the FDA and the CDC, and will further undermine the little trust people have left in those organizations, but I digress.

Human data was collected on an as-yet unused booster for BA1 Omicron, but (apparently) that data, while showing a jump in antibodies including against Omicron, was not particularly different than the antibody protection provided by the OG Covid vaccine (which is surely one reason why Pfizer did not even attempt to get that booster approved).  Thus, from a statistical standpoint, the authorization of the new booster is still questionable, even if we include the never-authorized original Omicron booster data as predictive of how effective the BA5 booster will be.

Except for political reasons (Biden promised an Omicron-specific booster in the fall), it's not clear why approval needed to be rushed -- why not do some human trials, or at least test antibody response in humans?  That should be relatively quick and not too costly (not that I feel bad about Pfizer/Moderna spending a few million for human trials on a drug they are making billions on).

So my advice regarding the Omicron-specific booster: there is no real evidence it is better than the original Covid vaccine booster (which you cannot get as a booster anymore, now that the new booster is available).

This leads to a second question, should you take any booster now?  For this question there is data available, not from human trials but from the CDC's data on real-world results.

I'll start with infection data, which should be viewed with a huge grain of salt.  Most people are not testing, and to the extent that people do test, there is a large bias toward those who are sicker.  There is also very likely a bias toward those who are vaccinated and boosted, as unvaccinated are not worried about Covid and thus will not test much (but will get tested if they are very sick and go to a hospital).   Ignoring the potential biases, the data indicate that the effectiveness a booster (vs vax only) actually leads to more infections(!) for all age groups.  Most scientists have concluded that the vaccine has little effect on infection or transmission at this point, so equality among vax vs boosted would not be a surprise.

Infection Rate per 100,000 per month

5-11             539           487             422
12-17             675           409             605
18-49          1,245           625          1,500
50-64          1,001           598          1,704
65+             827           577          2,528

So, if you're vaxed, the data says don't bother with a booster (of any sort) if you simply want to avoid infection.

How about avoiding serious disease or death?  The CDC publishes data on deaths, which is considered to be far less biased (because those who go to a hospital with Covid-like illness are tested for Covid).  I considered data for the summer (May through July - August is not available yet), when BA5 was the primary variant circulating.  Deaths are exceedingly rare for all but those 65+, and there is no apparent benefit (<1 in 100,000) from a booster for those under 65. 

Death Rate per 100,000 per Month
5-11              0.1            0.1              0.4
12-170.0  0.00.0
18-49              0.0            0.0              0.1
50-64              0.6            0.8              3.3
65+              7.2            9.4            38.9

For those 65+, there is a small effect of the booster (25% effective).  This translates about 2 additional deaths per month for vaxed versus boosted per 100,000 people over 65. In terms of individual risk, it's 1 in 14,000 if boosted vs. 1 in 10,000 if just vaxed (and about 1 in 2,500 if unvaxed), much lower for all categories than at other times in the pandemic, probably due to the fact that many susceptible have died and many others  already have protection even if unvaxed because they got Covid).

From the data, the conclusion is: don't bother with any booster if you're under 65.  For over 65, there may be a very small benefit.