How well are vaccines and boosters really protecting against COVID-19 deaths?

Israel MoH publicly posted daily COVID-19 death data split by unvaccinated, boosted, and vaccinated-not-boosted from Aug10-Sept8

Here are results of my analysis of these data
1/n
Summing over all days, it is not promising to see so many COVID-19 deaths in vaccinated/boosted groups.
But by now we know better than to draw conclusions from raw counts, right?
2/n
The Israeli MoH dashboard provides enough information to infer total proportion of population unvaccinated, boosted, or vaccinated-by-not-boosted, so we can compute normalized COVID-19 death rates in these groups.

3/n
From these, we can compute overall estimates of vaccine/booster effectiveness(VE) in preventing COVID-19 deaths relative to unvaccinated.

These overall VE estimates are VERY low; some might infer from this the vaccines and boosters are NOT protecting vs. COVID-19 deaths.
4/n
But don’t forget Simpson’s Paradox.

We see much lower vaccination/booster rates in the young, who also have MUCH lower rate of COVID-19 death.

This confounding of age might distort the overall VE estimates, so let’s compute separate estiamtes for each age group.
5/n
VE estimates by age are much higher than overall, showing indeed there was a strong Simpson effect.

Before interpreting these results, however, we need to consider one other thing: Do the <60yr data include children and, if so, should we pull them out into their own group?
6/n
Given the total counts for all ages sum to >9.1m, the total Israeli population, it is clear children are among the <60yr group, and we can infer the number <12yr from the MoH data.

They are unvaccinated, and unlikely to comprise any of the 23 COVID-19 deaths.
7/n
Splitting children out dramatically affects the VE estimates for the <60 group as well as overall.

It is CRUCIAL to separate children out when looking at vaccine effectiveness, since they cannot be vaccinated and have the lowest risk of advanced COVID-19 events.
8/n
Now consider the results.

For older group, we see vaccines reduced risk of COVID-19 deaths during this time period without boosters, but boosters clearly increased level of protection.

This is consistent with published papers showing early results from boosting.
9/n
For younger group, we see high protection vs. COVID-19 deaths from vaccines, and in these data no evidence boosters improve protection.

However, given only 7% boosted and not much time passed, it is possible that future data will show a booster benefit for young adults.

10/n
Repeating this analysis on “critical COVID-19 disease”, we see similar results.

The vaccines protect against critical disease, with older adults showing potential waning of efficacy improved by boosters, & younger adults showing strong protection irrespective of booster.

11/n
Two key caveats in these data:
1. It is not clear how this MoH data set counted individuals partially vaccinated with a single dose.
2. Also, MoH did not separate previously infected, who are either unvaccinated or partially vaccinated, which could attenuate VE estimates.

12/n
While informative, this analysis is limited given lack of access to important confounders other than age; Israeli research groups w/ access to more complete data can do more rigorous analyses.

Article detailing all calculations & more conclusions:
13/n
covid-datascience.com/post/what-do-n…

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More from @jsm2334

15 Sep
Data presented below show nearly 33% of unvaccinated adult Israeli residents were previously infected.

Why is this important & has this contributed to misinterpretation of Israeli data?

This thread wll explore these questions.
1/n
Israeli MoH releases periodic vaccination reports on its Telegram site. This table breaks down vaccination status by age groups as of September 14, 2021 listing total population and number given 1/2/3 doses plus those unvaccinated but recovered from previous infection
2/n Image
From these data, I constructed this table with % of population unvaccinated, given 1 dose, 2 doses, & 3 doses, & proportion of unvaccinated are previously infected.

Note that >30% of total unvaccinated Israelis were previously infected, & >1/3 for all age groups in 20-59yr
3/n Image
Read 11 tweets
15 Sep
I have seen a lot of people obsessing with Table 5 of the 8/21 UK Delta report:

402 Covid deaths among 47,008 fully vaccinated for case fatality rate 0.86%

253 Covid deaths among 151,054 unvaccinated for CFR=0.17%

Do vaccines increase CFR 5-fold?
1/4
assets.publishing.service.gov.uk/government/upl…
They also split data out by age (<50/>50).

For older group, CFR for vaccinated (1.81%) is 3.3-fold LOWER than CFR for unvaccinated (5.96%)

For younger group, CFR for vaccinated (0.05%) is 1.5-fold higher than CFR for unvaccinated (0.03%), but there are only 13 deaths.
2/4 Image
Another case of Simpson's paradox, since a confounding factor (age) is STRONGLY associated with both outcome (death) and exposure (vaccination status) given risk of death in old >>> young and vaccination rate old >>> young.
3/4
Read 5 tweets
24 Aug
New medRXiv paper by UPenn group led by John Wherry looking at immune markers 6m after vaccination.

Partially explains waning vaccine efficacy vs. infection, more durable vaccine efficacy vs. severe disease, and is relevant to current booster policy.

biorxiv.org/content/10.110…
Paper measured immune markers (antibodies, T-cells, B-cells) from 61 individuals vaccinated with Pfizer/Moderna at 6 time points, from pre-vax to 6m post-vax.

16 were previously infected with SARS-CoV-2 and 45 SARS-CoV-2 naïve, and analysis was stratified by previous infection.
The key results were:
1.Neutralizing antibodies (NAbs) decreased over time
2.Memory B cells (Bcells) increased over time and did not wane
3.Helper T cells (T4) and Killer T cells (T8) dynamic described
Read 14 tweets
24 Aug
Great tweet by Monica Gandhi on new paper on transmission using the best way to track transmission: attack rate of virus after exposure in a rigorous contact tracing setting.

A few comments about what this might mean for transmissibility of breakthrough infections...
Although not dealing with breakthrough vs. unvaccinated infections, two results that are encouraging for the notion that breakthroughs might transmit less:
1. Asymptomatic infected were >4x less likely to transmit to others than symptomatic.

We know breakthrough cases are more likely to be asymptomatic, so this suggests one reason why breakthroughs might transmit less ...
Read 7 tweets
18 Aug
@CT_Bergstrom I agree Carl.
I will write a blog post on this but one possibility is that this is a combination of
1. unmeasured confounders (eg that young people vaccinated in January are Health care workers who are tested and exposed much more than those later vaccinated young people)
@CT_Bergstrom 2. Delta effect. Since we know delta spreads faster & with 50-100x viral load, it makes sense this higher viral exposure could lead to detectable virus that would produce “asymptomatic breakthrough infections” if testing done at right time, even if the vaccine works as intended
@CT_Bergstrom 3. And based on data I’ve seen showing memory B cells and helper T cells remain maxed out at 6m (and can produce new nAbs in 2-3 days)and nAbs and killer T cells decrease 10x but still remain 10-100x prevaccine baseline, it is possible that in early months the circulating nAbs..
Read 5 tweets
17 Aug
Many are confused by results that >1/2 of hospitalized in Israel are vaccinated, thinking this means vaccines don't work. I downloaded actual Israeli data datadashboard.health.gov.il/COVID-19/gener… and show why these data provide strong evidence vaccines strongly protect vs. serious disease (1/8)
2/8
3/8
Read 15 tweets

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