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
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
Why does this matter? Because literature is clear they have strong immune protection even if not vaccinated (see post link below).

As a result, VE estimates will be strongly attenuated if previously infected are not removed from the unvaccinated.
4/n

covid-datascience.com/post/overwhelm…
To illustrate this effect, consider a populaton of 1m, 75% vaccinated, 1/3 unvaccinated previously infected, infection rate of 0.01 for unvaccinated no previous infection, VE=65%, and previous infections reduce risk of reinfection by 90%. Here is the effect:
5/n
We see failure to remove previously infected attenuates VE from 65% to 50%. Here is the same scenario assuming VE=50%, that is attenuated to 28.6% if previously infected are not removed from unvaccinated.
6/n
This is relevant since MoH reported in late July VE reduced to 44% for vax in Feb & 16% for vax in Jan, creating impression that vaccine effectiveness was going to 0% quickly after 6m.

Their report didn’t mention if they removed previously infected.
7/n
gov.il/BlobFolder/rep…
Three rigorous studies were done (Mizrahi et al,Israel et al,Goldberg et al) on waning immunity – all removed previously infected & adjusted for confounders as much as possible. Here is the Goldberg paper that also compared with unvaccinated controls.
8/n
medrxiv.org/content/10.110…
These all found 1.6-2.2x reduction in VE from those vaccinated in Jan-Feb vs. Apr-May, but relative to unvaccinated, VE reduced from 75-80% to 50-65%., much higher than the 44%/16% MoH reported

Is it possible MoH report mistakenly left previously infected in unvaccinated?
9/n
Since Israel made vax optional for previously infected and then only gave 1 dose, this especially affects the unvaccinated group. Other places, there could be some subset of “fully vaccinated” who were also previously infected and have extra protection.
10/n
For this reason, all locales should, whereever possible, split out data not just by vaccination status but also previous infection status.

And we should all be mindful of this potential effect when evaluating simple analyses to estimate VE.
11/n
BTW thanks to Nurit Baytch who sent me link to MOH methodology document showing in their analyses they DO remove unvaccinated from the strata before estimating VE: t.me/MOHreport/8321
... hopefully they did that for this waning immunity analysis: gov.il/BlobFolder/rep…

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More from @jsm2334

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
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 6 tweets
12 Sep
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
Read 13 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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