Israel: single Pfizer injection less effective than thought

[cormanr7]

Israel, which by now has vaccinated about 1 in 4 people (far ahead of any other country), has reported some 'real-life' preliminary data on the effect of the Pfizer vaccine after one shot. Comparing 200,000 vaccinated and a similar number of non-vaccinated persons (all over age 60) it was found there was no effect on positivity rate (positive/total tested by PCR) for the first two weeks. 'On day 14, the positivity rate dropped by 33% in the vaccinated group'. People who had received a second shot, however, had a very large increase in antibodies. These observations may be especially relevant to some countries  that have decided to postpone the second shot in order to vaccinate more people with the limited supply of doses available (like UK, who claimed that 89% efficacy was expected after one shot though I think Pfizer said it was 52%)

 https://www.theguardian.com/world/2021/jan/19/single-covid-vaccine-dose-in-israel-less-effective-than-we-hoped,     https://news.sky.com/story/covid-19-real-world-analysis-of-vaccine-in-israel-raises-questions-about-uk-strategy-12192751.

Israel has a high infection rate - with an increasing percentage due to the 'UK variant'- so it is likely that many in the vaccinated group got infected before sufficient immunity was build up. Also, in younger people, the response might be not the same. But there are unanswered questions: It is not clear what happened with the positivity rate between day 14 and 21 (presumably it stayed at 33%?) and afterwards. It is possibly too early to answer that anyway as vaccination started on December 20th. 

Edited January 20, 2021 by cormanr7
add sentence

[philba]

13 minutes ago, cormanr7 said:

Israel, which by now has vaccinated about 1 in 4 people (far ahead of any other country)

 

They've only got a population of about 9 million, so easy to hit those kind of figures.

 

If the UK had the same population, they'd have vaccinated about 1 in 3.

[rabas]

1 hour ago, cormanr7 said:

Israel, which by now has vaccinated about 1 in 4 people (far ahead of any other country), has reported some 'real-life' preliminary data on the effect of the Pfizer vaccine after one shot. Comparing 200,000 vaccinated and a similar number of non-vaccinated persons (all over age 60) it was found there was no effect on positivity rate (positive/total tested by PCR) for the first two weeks. 'On day 14, the positivity rate dropped by 33% in the vaccinated group'. People who had received a second shot, however, had a very large increase in antibodies. These observations may be especially relevant to some countries  that have decided to postpone the second shot in order to vaccinate more people with the limited supply of doses available (like UK, who claimed that 89% efficacy was expected after one shot though I think Pfizer said it was 52%)

 https://www.theguardian.com/world/2021/jan/19/single-covid-vaccine-dose-in-israel-less-effective-than-we-hoped,     https://news.sky.com/story/covid-19-real-world-analysis-of-vaccine-in-israel-raises-questions-about-uk-strategy-12192751.

Israel has a high infection rate - with an increasing percentage due to the 'UK variant'- so it is likely that many in the vaccinated group got infected before sufficient immunity was build up. Also, in younger people, the response might be not the same. But there are unanswered questions: It is not clear what happened with the positivity rate between day 14 and 21 (presumably it stayed at 33%?) and afterwards. It is possibly too early to answer that anyway as vaccination started on December 20th. 

 

A sudden 33% drop at day 14 sounds like a sampling effect of some sort.

 

It will also be interesting to see if efficacy against the UK B.1.1.7 is any weaker.  But B.1.1.7 is so last yearish. A bigger worry may be the Brazilian P.1 strain spreading through a population that should already have high immunity from the first wave.

[rabang]

The vaccine efficacy percentages are overhyped anyway and will cause a lot of grief and disappointment when the mass vaccinations really get underway. Any fool should understand they don't work the same in big pharma testing and in real life. Flu vaccines can have efficacy of 20 or 30 percent only. Virus mutations, massive scale of the operation etc. mean that this mess will take a long time to solve.

[cormanr7]

1 hour ago, rabang said:

The vaccine efficacy percentages are overhyped anyway and will cause a lot of grief and disappointment when the mass vaccinations really get underway. Any fool should understand they don't work the same in big pharma testing and in real life. Flu vaccines can have efficacy of 20 or 30 percent only. Virus mutations, massive scale of the operation etc. mean that this mess will take a long time to solve.

Agreed, but there are plenty people out there who are not aware of this or simply dismiss it and believe that by mid year everything will be cosy again. 

UK should have some data by now, but maybe they are not to keen on publishing it.

 

[rabas]

3 hours ago, rabang said:

The vaccine efficacy percentages are overhyped anyway and will cause a lot of grief and disappointment when the mass vaccinations really get underway. Any fool should understand they don't work the same in big pharma testing and in real life. Flu vaccines can have efficacy of 20 or 30 percent only. Virus mutations, massive scale of the operation etc. mean that this mess will take a long time to solve.

 

In fact, the term efficacy only applies to trials anyway. It's determined by ratios of vaccinated and un-vaccinated control groups.  The term used for vaccine performance in general is 'effectiveness'.  

 

It's unlikely to be over in 6 months, the rate of infections is still climbing and significant mutations are increasing.  Another new one from Kenya today.

[cormanr7]

23 minutes ago, rabas said:

 

 

It's unlikely to be over in 6 months, the rate of infections is still climbing and significant mutations are increasing.  Another new one from Kenya today.

For those interested, BBC future has an article on mutations and some potential trends:

https://www.bbc.com/future/article/20210119-covid-19-variants-how-the-virus-will-mutate-in-the-future

[Patong2021]

16 hours ago, rabang said:

The vaccine efficacy percentages are overhyped anyway and will cause a lot of grief and disappointment when the mass vaccinations really get underway. Any fool should understand they don't work the same in big pharma testing and in real life. Flu vaccines can have efficacy of 20 or 30 percent only. Virus mutations, massive scale of the operation etc. mean that this mess will take a long time to solve.

You take the data out of context and misinterpret. it is not difficult to see if one looks at key facts;

-Flu vaccine is made using the strain that health professionals expect will appear. Sometimes the formula is not matched for the strain infecting people. Human error, not vaccine defect.

-flu vaccine is old technology and not same concept as new mRNA technology vaccine. mRNA will be more strain specific.

-2 goals of flu vaccine is to reduce the risk of flu illness overall and to reduce impact of infection if infected so person does not have to go to hospital. Depending on virus vaccinated against,40%-60% effective.

- flu vaccine is more effective against influenza B and influenza A(H1N1) viruses and less effective against  influenza A(H3N2) viruses.

 

 

[mommysboy]

I think the problem was over-hype first started when Pfizer announced near 95% protection from infection.  I just think the definition and testing of mild infection became blurred, and it's likely that many borderline cases were missed in some trials. 

 

It also needs to be said that Pfizer has already condemned the one shot policy for its vaccine which greatly benefits from the additional dose, whereas the AZ second shot is more of a consolidation shot.

 

I've stated many times that the wrong metric was chosen anyway.  Really the only cast iron data concerns prevention of serious infection and death.  All vaccines seem to perform equally as well in this regard.

 

 

[cormanr7]

New data from Israel, this time from health provider KSM Maccabi. Sample consisted of approx. 51,000 people, all 60+. They had been vaccinated Dec 19-24 and were followed up to day 23 (that is 2 days after the second shot). Results: both confirmed new infections and hospitalizations (smaller sample, no details) decreased by about 60%, with no effect in the first 13-14 days and then a gradual decrease to a plateau at ca.40% vs the control group. You can read the story here: https://www.dailymail.co.uk/ news/article-9179677/Israeli-healthcare-group-says-coronavirus-infections-plunged-vaccinated-60s.html

[rabas]

48 minutes ago, cormanr7 said:

New data from Israel, this time from health provider KSM Maccabi. Sample consisted of approx. 51,000 people, all 60+. They had been vaccinated Dec 19-24 and were followed up to day 23 (that is 2 days after the second shot). Results: both confirmed new infections and hospitalizations (smaller sample, no details) decreased by about 60%, with no effect in the first 13-14 days and then a gradual decrease to a plateau at ca.40% vs the control group. You can read the story here: https://www.dailymail.co.uk/ news/article-9179677/Israeli-healthcare-group-says-coronavirus-infections-plunged-vaccinated-60s.html

The big take away is that Pfizer's mRNA  vaccine is excellent at stopping infections as well as reducing severe illness.

 

A few snake oil folks had been claiming Oxford's vaccine stopped infections better only because Pfizer didn't measure it! However, both types generate immunity in the same way. Thus,  mRNA vaccines' higher efficacy will stop infections better.

 

mRNA vaccines stand tall.

 

Edited January 24, 2021 by rabas

[onebir]

16 minutes ago, rabas said:

The big take away is that Pfizer's mRNA  vaccine is excellent at stopping infections as well as reducing severe illness.

60% is quite a bit lower than >90% though. I think that latter figure could still be valid though:

1) IIRC the stage 3 trials used people under 60 (so in effect, Israel has conducted a trial on almost ALL of a previously more or less untested subgroup. Good idea? I think not...)

2) The 'plateau' is only apparent between days 23 & 24, and is only apparent in infections - hospitalisations dropped further, maybe as much as 20% between those days (impossible to say exactly how much due to rounding error).

3) The results aren't controlled or blinded, in particular vaccinated people may have changed their behaviour, and given the information available about the lags before protection is achieved,  may have made greater changes in the latter part of the period.

 

So efficacy might well be closer to 90%, particularly for a younger population &/ over a longer period.

[rabas]

7 minutes ago, onebir said:

60% is quite a bit lower than >90% though. I think that latter figure could still be valid though:

1) IIRC the stage 3 trials used people under 60 (so in effect, Israel has conducted a trial on almost ALL of a previously more or less untested subgroup. Good idea? I think not...)

2) The 'plateau' is only apparent between days 23 & 24, and is only apparent in infections - hospitalisations dropped further, maybe as much as 20% between those days (impossible to say exactly how much due to rounding error).

3) The results aren't controlled or blinded, in particular vaccinated people may have changed their behaviour, and given the information available about the lags before protection is achieved,  may have made greater changes in the latter part of the period.

 

So efficacy might well be closer to 90%, particularly for a younger population &/ over a longer period.

1.  It was tested on older folks. Pfizer used a wide age range in phase 3, reporting group efficacy for  those > 65y and those > 75y.

 

2. Yes, I doubt the plateau is real because the numbers are averaged. The curve surely continues down.

 

Phase 3 was the controlled study. From here on, it will be real world numbers and these are particularly encouraging. Especially since this group was all over 65.

 

https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-publication-results-landmark

[onebir]

29 minutes ago, rabas said:

Pfizer used a wide age range in phase 3, reporting group efficacy for  those > 65y and those > 75y.

Ok but did they report a difference in efficacy between those groups?

[rabas]

18 minutes ago, onebir said:

Ok but did they report a difference in efficacy between those groups?

Very little. They reported

-- 94% for  the group > 65 years, which includes those >75

-- they reported  efficacy was  relatively uniform across all age groups.

-- And this quote: from here

 

"The Pfizer study presented estimates of the effectiveness in older people and found efficacy >90% in >55, > 65 and >75 year olds, though confidence intervals were wider in the older age groups.

 

That suggests ~90% on  >75y olds. 

 

[Virt]

Until Pfizer steps up the production, it's understandable why some consider the 1 dose strategy if they can vaccinate 100 % more people at the cost of 4 - 35 % drop in reduction of getting covid-19. 

 

Not perfect, but overall it should still protect more people from getting hospitalized. 

 

We have quite a few examples of senior citizens here in Denmark that got covid-19 after their first shot (which is only natural since it's not 100 % plus takes time to develop anti bodies) , but none of them died yet from covid-19 as far as I know, so if the vaccine prevents seriously illness even after first shot that has lower % reduction, that's a huge plus. 

 

In the perfect situation Pfizer could deliver enough vaccines, but since they can't i can see why some look for an alternative solution. 

 

I would rather run around with 1 shot of Pfizer vaccine in me compared to nothing. 

 

 

[mommysboy]

16 hours ago, rabas said:

The big take away is that Pfizer's mRNA  vaccine is excellent at stopping infections as well as reducing severe illness.

 

A few snake oil folks had been claiming Oxford's vaccine stopped infections better only because Pfizer didn't measure it! However, both types generate immunity in the same way. Thus,  mRNA vaccines' higher efficacy will stop infections better.

 

mRNA vaccines stand tall.

 

 

Really! Who said the Oxford vaccine was better?  Pointless picking out a few nuts.  Most rightly say it is not as good, but is still equally as effective at preventing serious illness is cheaper, easier to make, store, handle, and distribute.

 

The mRNA vaccines are excellent at stopping severe illness, and good at stopping infection, and we don't know about transmissibility.

 

I don't think we should make claims yet about infection rates and transmission.  It would be best if we instead celebrated the fact that there are numerous vaccines that prevent the infected individual from dying.

 

Honestly, given that MRNA they are new I would prefer the Oxford jab, and possibly even the Sinovac (subject to safety data).  I would take the Pfizer jab however if offered, but it must be in expert hands because it is so fragile.  Badly handled in a hot country it could easily become ineffective.

 

 

 

 

Edited January 25, 2021 by mommysboy

[mommysboy]

On 1/20/2021 at 11:02 AM, cormanr7 said:

Agreed, but there are plenty people out there who are not aware of this or simply dismiss it and believe that by mid year everything will be cosy again. 

UK should have some data by now, but maybe they are not to keen on publishing it.

 

 

Cases are certainly dropping now, though it is difficult to know if this is because of social distancing or vaccination, or both.  One vaccine has been out in small numbers for only 6 weeks, the other for just 3 weeks, so to read in reluctance is silly at this stage.

[rabas]

46 minutes ago, mommysboy said:

The mRNA vaccines are excellent at stopping severe illness, and good at stopping infection, and we don't know about transmissibility.

Excellent at stopping infection is an observation from the Israeli study. It is also well established that infectivity depends heavily on viral load, in general. Thus, transmissibility from a mild illness is lower. A person who was not infected has a very low chance of transmitting the disease.

 

 

46 minutes ago, mommysboy said:

I don't think we should make claims yet about infection rates and transmission.  It would be best if we instead celebrated the fact that there are numerous vaccines that prevent the infected individual from dying.

The science concern is now refocusing on the many recent mutations. Mutations like UK's B.1.1.7 likely arise from treating long term cases with strong medications that don't quickly kill the virus.

 

For the same reasons they now worry that leaving people in a state of partial immunity could cause the same on a wide scale. Oops.  Partial immunity comes from weaker vaccines (Sinovac) or  delaying second doses. Supply issues for all vaccines and AZ's plan to delay a second dose  to boost effectiveness are in focus.

 

Edited January 25, 2021 by rabas

[mommysboy]

3 hours ago, rabas said:

Excellent at stopping infection is an observation from the Israeli study. It is also well established that infectivity depends heavily on viral load, in general. Thus, transmissibility from a mild illness is lower. A person who was not infected has a very low chance of transmitting the disease.

 

 

The science concern is now refocusing on the many recent mutations. Mutations like UK's B.1.1.7 likely arise from treating long term cases with strong medications that don't quickly kill the virus.

 

For the same reasons they now worry that leaving people in a state of partial immunity could cause the same on a wide scale. Oops.  Partial immunity comes from weaker vaccines (Sinovac) or  delaying second doses. Supply issues for all vaccines and AZ's plan to delay a second dose  to boost effectiveness are in focus.

 

 

What is distressing with the news these days is that we have one authoritative figure overly stating one thing, followed by another a few days later stating the opposite.  Inevitably we choose the one we prefer, and defend it to the hilt.  We can also be swayed by the media in our own country.  Some things that make sense to us don't pan out in actuality.  I mean, you would have thought people with mild or even no symptoms are less contagious, however these are precisely the people we don't fear being around, whereas the poor individual with 'a belter' goes home and stays there for a while.

 

Everything is speculation at the moment.

 

For my part, I have the nasty thought that by preventing rapid transmission through lockdown, we do actually encourage the virus to mutate because it hangs around for much longer than would be natural.  So eventually, even someone who has had the virus once before,  gets a second dose from a mutated variant.  I hope it's a scenario that won't play out.  Nevertheless, by getting as many people immune, even partly, by inoculation or natural infection will undoubtedly drastically reduce serious illness.  

 

Mutation is something that happens.  Extrapolating from the behaviour of a bacteria might be unwise when it comes to a virus of this nature- it seems to happen all by itself as a process of evolution when the virus meets antibodies that don't kill it quickly as you say. Unfortunately, none of these vaccines are 'sterilizing'.  They are not a magic bullet but they will do a lot of good.  Even a seemingly modest success rate, as with the flu vaccine seems to have a dramatic effect in specific cohorts like the elderly.

 

 

 

 

 

[cormanr7]

Regarding the 60% reduction mentioned in my post above, this was established just one or two days after the second dose, so it may be too soon to establish 'final' efficacy. The Pfizer data of 95% were obtained one week after the second shot.

For those wondering about age distribution, actual results per age group, etc., the Pfizer-BioNTech phase 3 trial report is here:  

https://www.nejm.org/doi/full/10.1056/NEJMoa2034577. Data for the various age groups are shown in Table 3

and indicate no statistical difference between those 16-55 years, more than 55 or more than 65 years, it all falls in the range of 94-96%. However, the older than 65 years group has a low numbers of cases and a much larger 95% confidence interval. Whereas the articles says that 42% of participants was over 55 it does not detail how many were over 65 (might be in the supplements, I have not checked). Median age was reported as 52 with range 16-89. So definitely it was not tested on younger people only.

Finally the 'English' and South African mutants have appeared in Israel https://www.aljazeera.com/news/2021/1/25/israel-closes-skies-to-air-travel-as-covid-variants-found  and may have had some effects on the results as they spread much faster, but I do not know if they make up a significant fraction of recent infections. 

Edited January 25, 2021 by cormanr7
add final sentence

[mommysboy]

6 hours ago, cormanr7 said:

Regarding the 60% reduction mentioned in my post above, this was established just one or two days after the second dose, so it may be too soon to establish 'final' efficacy. The Pfizer data of 95% were obtained one week after the second shot.

For those wondering about age distribution, actual results per age group, etc., the Pfizer-BioNTech phase 3 trial report is here:  

https://www.nejm.org/doi/full/10.1056/NEJMoa2034577. Data for the various age groups are shown in Table 3

and indicate no statistical difference between those 16-55 years, more than 55 or more than 65 years, it all falls in the range of 94-96%. However, the older than 65 years group has a low numbers of cases and a much larger 95% confidence interval. Whereas the articles says that 42% of participants was over 55 it does not detail how many were over 65 (might be in the supplements, I have not checked). Median age was reported as 52 with range 16-89. So definitely it was not tested on younger people only.

Finally the 'English' and South African mutants have appeared in Israel https://www.aljazeera.com/news/2021/1/25/israel-closes-skies-to-air-travel-as-covid-variants-found  and may have had some effects on the results as they spread much faster, but I do not know if they make up a significant fraction of recent infections. 

 

Actually, a 60% reduction is in any case really good, because of the profile of the people being vaccinated.  The really important statistic would be the reduction in hospitalizations. 

 

Herd immunity will be difficult to achieve in many countries.  It could be done in Australia with an mRNA for instance, because of the relatively low population, first class facilities, and high compliance.  Nevertheless, to ensure that immunity you can't really open up to inward travel because sooner or later a new variant will undo all the good work.  So you end up having to make the same incredible effort year in year out.  Currently, the mRNA vaccines are a logistical nightmare.  In the UK, the vaccination drive only really gathered pace when the Oxford jab became available. But of course this vaccine is not as effective, and likely couldn't get a country near herd immunity.

[cormanr7]

Some more results dripping in from Israel: Maccabi reports that fewer than 0.01% people (20 out of 128,600) that received two Pfizer shots  have contracted COVID one week after the second shot. None of these have been hospitalized so far  https://www.reuters.com/article/health-coronavirus-israel-vaccines/early-results-on-pfizer-covid-19-vaccine-encouraging-says-israeli-hmo-idUSL1N2K01Y4.

Article neglects to mention one important fact though: the exposure time has been very short, it remains to be seen what results are in one month, half a year....and it also not clear how many non-vaccinated people were infected over the same period.