Post #1196: COVID-19 hysteresis

 

Hysteresis, not hysteria.

Webster’s Dictionary defines hysteresis as “a retardation of an effect when the forces acting upon a body are changed …”.  Wikipedia offers a different take on it, that “Hysteresis is the dependence of the state of a system on its history.” 

No matter which way you look at it, a system with hysteresis is one that clings to its recent past, and does not change fully to reflect current conditions. Continue reading Post #1196: COVID-19 hysteresis

Post #1192: Randomized clinical trial results demonstrate that COVID-19 vaccines remain effective for at least six months.

I recent posts I’ve discussed results released by the Israeli Ministry of Health last week.  These got a lot of press because they appear to show a rapid decline in immunity from COVID-19 vaccines.  The Israelis inferred that immunity to infection was almost gone after six months.

That was an extraordinary result, and got a lot of attention because if it were true, it would have serious implications for health policy.

As I discussed those results, I hope I made it clear that the methods used in the Israeli study were weak.  That wasn’t a controlled trial, it was “observational data”, contrasting cohorts of Israelis based on what month they had been vaccinated.  Those cohorts differed not just in terms of how long ago they were vaccinated, but also in terms of health risk, age, and occupational mix.

Earlier today, I went looking for any evidence of that rapid dropoff in immunity in Virginia’s data.  I couldn’t find it. Near as I can tell, there’s been no uptick in breakthrough infections in Virginia, despite the onset of the Delta wave of COVID-19.

We now have direct evidence from a randomized, controlled clinical trial that immunity from the Pfizer vaccine remains high for at least six months.  That’s based on research that was reported today.  You can see the original research at this link.

Here’s the key table, below.  Yes, the effectiveness of the vaccination falls somewhat over time.  But no, it does not plummet.  If falls off at a fairly modest rate, comparable to other vaccines.  The authors of the study characterize it as declining roughly 6 percent every two months.  This is what I would call a perfectly normal result for a vaccine:

Source:  Six Month Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine,

Once you develop full immunity, the efficacy of the vaccine in preventing a symptomatic COVID-19 infection is:

  • 96% effective in months 1 and 2.
  • 90% effective in months 3, and 4.
  • 84% effective in months 5 and 6.

Over the entire six-month period, the vaccine had an average effectiveness of 91% in preventing symptomatic disease, and 97% effectiveness in preventing severe disease.  (There was no testing to see the extent to which it prevented asymptomatic infections).

The method used here is the gold standard.  It’s a double-blind randomized trial with placebo.

This randomized clinical trial is a far more reliable way to estimate the effectiveness of the vaccine than the “observational data” studies from Israel and other places.  Here, we can be certain the vaccinated and unvaccinated groups are otherwise identical (to within sampling error), because individuals were randomly assigned to one group or the other.  By contrast, in the Israeli study, the groups vaccinated in January and June were vastly different in terms of age, risk, and occupational mix.  The resulting differences in breakthrough infection rate for those two groups (one with vaccination just one month old, one with vaccination six months old) reflected not just the age of the vaccination, but also any effects of the large difference in risk, age, and occupational mix between those two groups.

The only uncertainty left is whether there is something unique about the Delta variant that would invalidate these results.  The prevalent strains in the locations and time that this study took place did not include Delta.  But I think it’s not plausible to suggest that these results held for all of the strains in circulation at the time, but that, uniquely, there would be a big dropoff in immunity for Delta (and only Delta).  That is especially given that he vaccines are known to be effective against Delta, just not quite as effective as they were against the native strain of COVID-19.  There’s no reason grounded in basic science to think that such a thing was possible, let alone likely.

I think this provides the definitive answer to the question “Do you need a booster shot at six months”.  The answer is no.  Protection against symptomatic disease remains good, protection against severe disease remains even better.  That’s what the controlled clinical trial now shows.

And, for sure, with these results, the U.S. is not going to approve booster shots at six months.  Not only do you not need it, but it’s not going to be possible to obtain it legally in the U.S.

It may be a coincidence that this research come out today in preprint (no-peer-reviewed) form.  But it may well be that this was hustled into preprint in response to the Israeli Ministry of Health findings that were released last week.  That would have been the right thing to do, to make it clear that the huge dropoff in immunity observed in the Israeli results was an artifact of methods, and was not a real effect.

With that cleared up, I will return to my task of calculating the odds of infection and harm, for the fully-vaccinated population, in this U.S. Delta wave.

Post #1191: Breakthrough infections in Virginia suggest little loss of vaccine-created immunity over time.

Background:  Why breakthrough infections suddenly matter.

Two posts ago (Post #1189), I went into the new findings from Israel regarding breakthrough infections of the Delta variant.  Their data suggest that by six months after the time of vaccination, the Pfizer vaccine has almost completely lost its ability to prevent infections with Delta.  It still does a good job of preventing hospitalization and death, just not infections.

I’m not sure if that’s a real result, or just an artifact of the way in which Israel went about vaccinating people.  Their sample size was small, and their results were odd in that younger people appeared to lose immunity at a much higher rate than the elderly.

The Israeli results aren’t from a clinical trial.  They come from comparing the current infection rates of cohorts of Israelis who were vaccinated in January, February, and so on.  The members of those cohorts aren’t randomly selected, but differ systematically.  The earliest cohorts (the persons vaccinated first) focused on high-risk individuals, the elderly, and health care workers.

The upshot is that by contrasting cohorts of individuals based on month of vaccination, you aren’t looking solely at the effect of time-since-vaccination.  You are also looking at the effect of being elderly, being at high risk, and working in the health care system.  Plausibly, some of those other factors would influence your odds of being exposed to Delta and picking up a breakthrough infection.

Some aspects of their results suggest that at least some of what they observe is an artifact of who was selected for those cohorts.  In particular, they found that immunity fades to a much greater degree among the non-elderly, which is the exact opposite of what you would expect, given the generally weaker immune response of the elderly.   (That weaker response is why there are annual flu shots specifically formulated for the elderly, with an enhanced dose designed to stimulate those aging immune systems).

That said, the finding is out there.  And if it’s true — if what the Israelis are seeing is in fact an indication that the vaccine’s protective effects fade profoundly within half a year — that has major implications for individuals and for our public health strategy.

But is it true, or just an artifact of their methods? 


Excellence in public data:  Virginia

Faced with something like this — some hazy finding, showing a huge and important effect, from a small number of cases, in a distant land, that nobody has seen before, using non-randomized data  — you get the drift — my first reaction is to see if anybody else says anything even remotely similar.  And I want to see that based on data that I understand and trust.

It seems to me that tracking breakthrough infections ought to be a piece of cake for U.S. states.  As I understand it, state health departments know which individuals have been vaccinated.  (There’s a caveat here for vaccines that flowed through various Federal programs, including the armed forces, Veterans’ Administration, and the U.S. Indian Health Service.  But states distributed the vast majority.)  For sure, state health departments know which individuals have had a positive test.  I’d be shocked if both lists didn’t contain the Social Security Number (SSN).  And even if not, name/gender/age/address is good enough to match up 99+% of those entries absent a unique identifier such as SSN.  (I speak from experience there, because figuring out how to make such “soft” merges between data files used to be part of my job.)

In short, all a state needs to do is match up the list of the vaccinated and the list of the infected.  The people who are on both lists constitute your breakthrough infections.  You’ll miss a few — individuals who moved into or out of state, individuals whose cases were dealt with by Federal rather than state systems — but in most states, those exceptions should be a trivial fraction of the population.

And so, for months now, I’ve wondered why states haven’t done that.

Turns out, Virginia has.  Virginia now has a web page devoted to tracking breakthrough infections.  It’s titled “Cases by Vaccination Status”, but that’s breakthrough infections.  And I sure wish other states would follow suit.

I’m going to take one paragraph to put in a plug for the Virginia Department of Health.  I’ve been using Federal, state, and sometimes local government data sources for more than a year now, tracking the pandemic.  Virginia’s public-facing data is head and shoulders above the rest.  A lot of times when I’ve wanted to discuss a national issue, I “illustrate” it with data from Virginia.  That’s because Virginia was the only place I could find the data files, publicly available, that would allow me to do it.  When you see that — when the data meet the analytical needs — you know that the people creating the data are almost certainly the same as the people who are using the data.  That’s how they end up providing usable data files.

In light of the Israeli findings, I would love to see Virginia’s data tabulated by month of vaccination.  Even though those monthly cohorts were not randomly selected, I’d at least like to see whether or not the crude finding that appears in the Israeli data — that breakthrough infections become common by six months after vaccination — before considering the Israeli results further.

But let me try to do the next best thing.  Let me at least look to see of those breakthrough infections are rising, as they plausibly should as the vaccinations age.  If the Israeli findings are true and not spurious.

In any case, by looking at the Virginia data for the past couple of weeks, we can be reasonably sure that, so far, as of about a week ago, breakthrough infections were uncommon here in Virginia.  This, despite a reasonably high fraction of the population being vaccinated.

Below, the breakthrough cases would be 1 minus the percentage shown.  So, in this case, (1 – 98.54% = ) ~ 1.5% of infections were breakthrough cases for fully-vaccinated individuals.  The remainder (98.54%) were among the un-vaccinated.

To interpret that, you need to realize that there’s considerable uncertainty around these numbers.  It’s not “statistical uncertainty”, because this is a census of cases, not a sample.  It’s more like “natural variation”, when small numbers of infections occur within a very large population pool.  Each number is a bit shaky, so to speak, but not because we’ve drawn a sample.  They are shaky just because there are so few of them and they may fluctuate from day to day.

In addition, you need to know that there is a strong age-related correlation in vaccination rate, hospitalization rate, and mortality rate.  So you can’t just take this raw count and infer that (e.g.) the vaccines are better at preventing infection than they are at preventing hospitalization.  That’s not true.  Arguably, the reason you’re seeing breakthrough cases as a higher fraction of hospitalizations than of infections is that hospitalization is strongly concentrated in the elderly, who have a very high rate of vaccination.  I’d have to age-adjust the infection and hospitalization numbers separately if I wanted to get a true apples-to-apples comparison of impact on infection versus impact on hospitalization.

What’s at issue with the Israeli findings is the infection rate.  So let me just state this plainly, and do a bit of math.  Almost all these infections are in adults, so let me focus on the adult population.

As of this most recent two-week period available, the fully-vaccinated population accounted for:

  • 64% of the adult population.
  • 1.5% of the infections.

Doing the math, that means that the observed effectiveness of the vaccines, against COVID-19, in Virginia, over this period, is:

(1.5/64) / (98.5/36) = <1%

(Ah, well, what I really mean to say is that the effectiveness is >99%.  The chance of getting infected is <1% of the chance for a non-vaccinated individual.)

In Virginia, during this most recent time period, if you were vaccinated, your chance of having a COVID-19 infection was less than one percent of the chance faced by an un-vaccinated person.

That’s substantially better than the clinical trials found.  So, no doubt there’s a behavioral aspect to number.  The vaccinated aren’t chosen at random, but instead are drawn from the rational population possessed of common sense.  The unvaccinated, by contrast, are largely a mix of the irrational and those ideologically-driven to reject the vaccine.  Almost without a doubt, the unvaccinated are also the ones who reject COVID-19 hygiene.

And so, this is probably best interpreted as saying that if you’re vaccinated and adopt common-sense COVID-19 hygiene measures, your risk of getting infected is less than one percent of the risk faced by those who can’t be bothered to do either.

In Virginia.  As of a couple of weeks back.

And so, whatever is driving those Israeli findings does not appear to have started happening here yet.

Now I need to ask a couple of more questions.

First, does this reflect the Delta variant?  I’d say yes.  I can’t find any direct measure of that, because CDC didn’t sequence enough samples to provide a state-level estimate for Virginia.  But I can infer it from the fact that this period is squarely in the middle of the current upsurge in cases in Virginia.

The pale blue lines mark the start and end dates used in the breakthrough calculation above.  Those increases didn’t really get going until Delta dominated, and Virginia is right in line with the rest of the South Atlantic states.  The CDC shows that, during this period, about two-thirds of cases in this region were the Delta variant.  Between those two pieces of evidence, I’m fairly confident in saying that the breakthrough rate above is largely reflective of Delta infections.

The next question to ask is, has this changed over time?  That’s easy enough to answer.  Let me set the dates to span an equivalent period on the downslope of the curve above, and see what the Commonwealth says the breakthrough infection rate was.

And the short answer is that breakthrough infection, as a percent of total, was actually higher at the start of June than it is now.  That’s a time period when the Alpha variant was still dominant.  Those accounted for 4.5 percent of total infections — in line with the clinical trials data — compared to less than one percent in the most recent period.

Here’s the kicker:  If you download yet another one of Virginia’s data files, you can readily calculate that 24% of Virginia’s vaccine doses were administered before March 1, 2021.

In other words, somewhere around one-quarter of Virginia’s vaccinated individuals fall into the categories that should be suffering a massive loss of immunity to COVID-19 now, if the Israeli results are true.  And yet, we are seeing no uptick in breakthrough infections.  To the contrary, based on the two time periods I looked at, those breakthrough infections actually fell.

My conclusion, based on publicly-available data from Virginia, is that whatever is happening in Israel surely does not seem to be happening in Virginia.  The Israeli findings shows a massive reduction in immunity for those whose immunizations were several months old.  If true, given that almost a quarter of Virginia COVID-19 immunizations are five months old or older, given the estimated effect from Israel, that really should have started boosting the rate of breakthrough infections by now.  And no such thing has happened.

This analysis could be done more cleanly by tabulating by date of vaccination, but that would require the person-level data that only the Commonwealth possesses.  I hope they’ll take a quick cut at that and make the results now.  Otherwise, these Israeli results would seem to through a monkeywrench into any planning for the pandemic.


Afterthought

I want to be clear that I think Israel’s Ministry of Health did the right thing in releasing their statistical analysis.  In fact, I’d say they were ethically compelled to do so.  And, based on the news reporting, the accompanying text (in Hebrew, which I cannot read) did mention all the relevant caveats, in that the monthly cohorts of the vaccinated were not randomly chosen.

It’s a tough call.

On the one hand, Israel was a couple of months ahead of most other countries.  If this result were real, they’d be the first to have it show up in their national data. And if it were real, they really would be compelled to offer a warning to other countries that might be subject to the same loss of immunity within a couple of months.

On the other hand, you don’t want to make health care policy based on spurious results.  (Though this would hardly be the first time that happened).  Consider the the expense and hassle of providing booster shots on a semi-yearly basis to the entire vaccine-accepting population.  Now consider the risk of doing that for no reason, if the Israeli result are spurious.  (And I note that Israel itself has not yet decided to do that, based on their own results.)

So it’s a tough call.  Alerting other public health agencies to this possibility seems like the right thing to do.  The US CDC and FDA aren’t going to make any sort of snap decision on booster shots.  They are going to gather the evidence, and make up their own minds.  And, based on what I can see in Virginia, they are going to find that the Israeli results are not replicated in other places.  That will tell them that the correlation observed there is an artifact of something about the Israeli experience and not a failure of vaccine-generated immunity.  And the scientific method will have done the right thing in filtering out fact from fiction.

Post #1190, no change in COVID-19 trend to 7/27/2021

 

No real change in trend, to speak of.  The U.S. now averages 19.5 new COVID-19 cases / 100,000 / day.

Extrapolating based on today’s data yields the following updated chart.  It’ll be between two and three weeks before we exceed the peak new case rate of the U.S. winter wave.

On the plus side, a reader has pointed out that the Missouri counties where this outbreak first took hold have definitely peaked.  Missouri as a state took longer because the outbreak had to spread elsewhere within that state.  But as of today, it definitely looks like Missouri is peaking.

Taking that as the pattern, I’m still expecting this wave to last about seven weeks, of which roughly four have already passed.  If that holds, this won’t get much worse than the peak of the winter wave, before it crests.  But if I had to guess, the risk is on the upside.  Given our slow response to the current wave, it would not surprise me if cases continued to rise for some period after that.

Needless to say, this is blind reasoning-by-analogy.  If you can find a more credible prediction, use it.

I’m now going to back to trying to asses the risks, for fully vaccinated individuals.  That’s a tough task, given the findings from Israel discussed in my last post.

On the one hand, if those results are true — if the effectiveness of the vaccines against a Delta infection fades to near nothing in six months — that changes all the calculations.  Vaccines still provide good protection against hospitalization and death, six months out.  But maybe not against infection per se.  And if vaccinated individuals can spread Delta fairly well if they are infected, that changes any “herd immunity” type calculation.

On the other hand, if those are spurious, and the world looks like the British results — immunity holds up well through six months — then the world is pretty much as I have described it in past posts.  Get vaccinated, and consider this pandemic a Darwin test for the unvaccinated.  And calculate your odds (of infection, hospitalization, death), and act based on your risk tolerance.

No matter who is right, it would be prudent to get yourself some N95s now, while they remain available through standard retail channels, if you don’t own some already.

Post #1189: Part 2B of the new COVID odds, the recent findings from Israel.

 

Today is the start of my “all things vaccine” series of posts.  I want some reasonably solid answers to  a handful of straightforward questions pertaining to U.S. individuals who are fully vaccinated against COVID-19.

For now, I’ll settle for answers to one thing:  What’s up with the data being reported from Israel?  In a nutshell, based on a small sample of cases, the Israeli Ministry of Health suggests that the Pfizer vaccine’s ability to protect against infection by the Delta variant shows a nearly linear decline over time, and is almost nil six months after vaccination.  Let me emphasize that finding is based on a very small sample, and that protection against hospitalization and death remain high, it’s only protection against “any infection” or “symptomatic infection” that appears to fall off rapidly in their data.

In this post, my goal is to channel the spirit of Light and Pillemer.  This all about research results that disagree.  It is not sufficient merely to say that results disagree, and shrug your shoulders.  The point of a review of the literature is to identify why they disagree, and figure out a way to test that.

I’ll give you my conclusion up front:  I’m not sure yet whether that Israeli finding is real, or is an artifact of methods.  But it sure has the “flavor” of a real finding.  There’s some modest evidence that maybe some of their result is due to having vaccinated the highest-risk individuals first.  (So that their earliest cohorts differ systematically from their later cohorts.)  And, oddly, the fading of immunity is far more pronounced in their younger population, which is exactly the opposite of what would be expected based on the weakening of the immune system with age.  But in the main, from what has been published, this has the appearance of being a true finding, including a rough dose-response relationship (immunity declines monotonically with time from vaccination).

So why hasn’t the U.S. found that?  Why haven’t the British found that?  Well, that’s plausibly because Israel was ahead of both of us in getting their population vaccinated.  The most profound loss of immunity in the Israeli data was for those fully vaccinated in January 2021.  Those individuals account for almost 20% of the Israeli population, but maybe a percent or two of the U.S. or British populations.  That was followed by those vaccinated in February 2021, and so on.  Because we were so late to vaccinate, compared to Israel, those cohorts aren’t a very large fraction of the U.S. or British populations, compared to their impact in Israel.

I’ll say something further:  Given how important this is, how large and rapid a deterioration of protection that Israel appears to have identified, and how huge a sample size of Delta-infected individuals we now have in the U.S.A., it should be a piece of cake for any large state with an outbreak to confirm or reject the tentative findings of the Israeli Ministry of Health.  Just match up the rosters of the vaccinated and those who tested positive, and cross-tabulate by month of vaccination.  If the results are as the Israelis suggest, the results will jump off the page.

Bottom line:  If I can figure that out, so can every state public health agency in the country.  It should not be long before the current uncertainty over this is settled.

If I had to summarize, I’d say that everyone agrees that the vaccines provide good protection, out to at least six months, against hospitalization (and probably against death) from Delta.  But there’s some evidence (from Israel, but not yet from elsewhere) to show that protection against any infection fades rapidly over that time period.  Separately, it’s now clear that those who have a “breakthrough” infection (i.e., infected despite being vaccinated) are perfectly capable of spreading the disease, just like anybody else who is infected.  (No surprise there.)  Though likely at a lower rate than the un-vaccinated.  But in the context of Delta, where viral loads appear very high, there may still be significant disease spread via breakthrough infections.

One part of this that I have not yet examined is how unusual those Israeli findings are.  Whenever something has been presented as some new aspect of COVID-19, what I have generally found is that other viruses do the same thing, it’s just that nobody ever much noticed.  (E.g., about 16 percent of flu infections are totally asymptomatic.)   I’m familiar with vaccines that require boosters at five-year intervals.  I’ve never heard of one that more-or-less wears off within six months.  Is there precedent for this or not, that’s a question I still need to research.

A final complication is the for-profit drug industry.  Based on what I read, the vaccine manufacturers are pushing hard for booster shots.  I can’t say the approval process is corrupt, but neither does it appear perfectly pure.  So, science aside, the force of money is behind concluding that booster shots are needed, and money can be a corrosive and corrupting force.

Here’s my take on it:  Exceptional claims require exceptional proof.   And now that the Israelis have found this, that finding should be replicated in short order.  Either Israel is the bellwether on this, because Israel vaccinated first.  Or those new Israeli results are an artifact of methods or (far less plausibly) simply small numbers of cases.  But it really should not take long for others to duplicate the basic result of an apparent and rapid decline in immunity against the Delta variant within during the first six months of immunization.


Does this mean you should get a booster shot?

Does this mean you should get a booster shot?  I’m not sure, and it’s not clear that you can get one in the U.S. at this point anyway.  That sort of thing requires FDA clearance.  Worse, it appears that the vaccine manufacturers are pushing for it, which means that there will be pressure to approve regardless of scientific merit.

There’s a cogent discussion of both sides at the University of Minnesota Center for Infectious Disease research and policy website.  It appears clear from that discussion that more-or-less the only evidence suggesting the need for a booster, at this point, is this recently released study of a small number of recent cases from Israel.  Hence, the Israeli results appear to play a pivotal role in the evolution of the booster shot issue in the near future.  Quoting CIDRAP:

Our official U.S. position on booster shots can be found at this URL.

Americans who have been fully vaccinated do not need a booster shot at this time. FDA, CDC, and NIH are engaged in a science-based, rigorous process to consider whether or when a booster might be necessary. This process takes into account laboratory data, clinical trial data, and cohort data – which can include data from specific pharmaceutical companies, but does not rely on those data exclusively. We continue to review any new data as it becomes available and will keep the public informed. We are prepared for booster doses if and when the science demonstrates that they are needed.

It gets back to that core question:  Is the effect the Israelis are seeing real, and neither we nor Great Britain is seeing it because we started vaccinating later?  Or is the Israeli effect some sort of artifact of methods, or a mere statistical fluke — plausibly because they vaccinated the most at-risk first?  That’s what FDA and CDC need to decide.  And I don’t think it ought to take them long to figure it out.


A quick summary of Israeli and British evidence so far.

If I pick up British studies of vaccine effectiveness, they seem to match what I expect to see.  And they roughly match the clinical trial results, plus or minus the usual differences between clinical trials and observational data.  And they match what I would call the consensus view in America, as well as matching what I would call the normal behavior of vaccines.

All of that research — both clinical trials and observational data — says the Pfizer and Moderna vaccines work pretty well, even against this new Delta variant.  And that immunity lasts for quite a long time.

In a nutshell, clinical trial data and observational data out of Great Britain suggest that the Pfizer vaccine is about 80% to 90% effective in preventing  symptomatic illness from the Delta variant.  And more effective than that at preventing severe illness, hospitalization, and death.

Here’s a table from their most recent vaccine surveillance report, available at this URL.  The results are a bit worse than the clinical trials estimate, but these are observational data — the people who did and didn’t get vaccinated might have been systematically different from one another.

Source:  British Ministry of Health, COVID vaccine surveillance report — Week 29, available at URL cited above.  Numbers are percents.

You have to go to their background methods document (at this URL) to get more information on methods, but even with that, there is no explicit mention of adjustments for age or comorbidities of the vaccinated population.  There’s just a passing mention that these effects did not vary much by age.

By contrast, there’s the information just released by the Israeli Ministry of Health.  Let me emphasize that this is  very new and based on few cases.  It boils down to “immunity to Delta mostly fades after six months” and as a corollary, overall immunity conferred against Delta is rather modest, once the vaccinated population ages into that six-months-plus state.  You can find the source document at this link.

As a result, the most recent press release from the Israeli Ministry of Health says that, at present, the Pfizer vaccine is only 41% effective in preventing symptomatic illness from the Delta variant. (Although, to be fair, that’s based on a tiny number of cases, and the 95% confidence interval is 9% – 61%).  But the vaccine remains quite effective at preventing severe illness and hospitalization.

Source:  Israeli Ministry of Health, URL cited above.

And, they get that result because they estimate that the protective effect of the vaccine fades rapidly over time.  Here’s the key graph.  The blue bar shows effectiveness of vaccine for those vaccinated on January 2021.

Source:  Israeli Ministry of Health, URL cited above.

So, what’s the true story?  Is the Israeli experience really different, or is this just an artifact of methods, or possibly even one of mis-reporting of the facts?

There are a few obvious differences between the British and Israeli experience.  The British used a mix of three different vaccines, while the Israelis used Pfizer only.  The British (I think) went in strict age order, while the Israelis prioritized the elderly, the high risk, and health care workers first.

But in this context, the main difference is that the Israelis were vaccinated earlier.  Their contingent of aged, fully-vaccinated individuals is a much higher proportion of the population.

At the end of January 2021, about 20% of the Israeli population was fully vaccinated.  At that same point, thanks in part to a British decision to prioritize the first shot over full vaccination, less than 1 percent of the British population was fully vaccinated.

And what about the U.S.A.?   Our experience is more like the British. We have relatively few vaccinated individuals who fall into those January and February cohorts.

That said, we have a huge population.  It seems like a simple cross-reference of vaccination rosters and test rosters could easily identify this cohort-age effect in the U.S.A.  Just take any large state with a lot of the Delta variant — California, say — match up the two lists, and check the breakthrough rate by month of vaccination.

Given our huge sample size compared to Israel, and the severity of the current outbreak, if the vaccine protection deteriorates to the degree shown in the Israeli findings, any large U.S. state ought to be able to identify that in a heartbeat. For sure, if I had access to the underlying data files, I’d have done it by now.


A few other thoughts.

These Israeli findings are from the same group that documented excellent success of the Pfizer vaccine against the Alpha variant (published in The Lancet.)  That suggests the likelihood of mere methodological error is small.  It also suggests that this change in due to the Delta variant (that is, they appear to have found no such effect for the Alpha variant).

In my limited experience, I’ve found that generational effects like this can arise in observational data for spurious reasons.  E.g., perhaps the people who opted in earliest are the ones most at risk.  Hence, during the next outbreak, they’ll have the worst results.

In this case, that’s clearly true.  Israel decided to vaccinate the elderly and those at high risk first.  (Along with health care workers).  As did most other nations, including the U.S.

In other words, there may be other risk factors that are correlated with the various monthly cohorts.  For example, if Delta was a particular problem for health care workers, the earliest cohorts if the Israeli vaccinated would show the highest rate of breakthrough infections.  That wouldn’t necessarily be due to fading of immunity. That could be due to the order in which occupations were given priority in vaccination.

I can only guess that the text of the document mentions this possibility.  That seems to be the gist of Fortune’s reporting of these results.  As I can’t read the text, I am not able to verify that.

In that regard, I note one oddity of the results:  This presumed “fading of immunity” effect for Delta is much more pronounced for those under age 60.  I would have thought, given that immune systems weaken with age, that it should have been the other way around.  If the vaccine-induced immunity is going to give out, you’d think it would give out first and most in the oldest.  But that was not true.

Source:  Israeli Ministry of Health, URL cited above.

From my experience, I can tell you something that I would like to see, if possible, from the Israeli Ministry of Health.  A lot of researchers find something where they expect to see it, and stop looking.  Few of them go on to make sure that they don’t find it where they don’t expect to see it.

Israel should repeat the analysis using the time period when the Alpha variant was dominant, if that is possible.  Pool the observations using a “proportional hazards” model if sample size is small.

If this apparent fading of immunity is really just a generational effect (an artifact of vaccinating the most at-risk first), that should have appeared for the Alpha variant as well.  But if it does not, that strongly increases the inference that this has something to do with the Delta variant, and is not an artifact of the ordering of vaccinations over time from most to least at-risk.

Finally, this isn’t my last word on this.  This is just getting the facts down on paper, and trying to figure out what causes the difference between the Israeli an and British findings.  I need to let all this percolate a bit before addressing it again.

Post #1188: The CDC finally awakens

 

Refer to Post #1175, from two weeks ago, for the background.

Today, easily two weeks after risk levels clearly and obviously exceeded those on May 13, 2021, the CDC has finally awakened to the current danger.  Sort of.  It is now being reported that the CDC will modify (not withdraw) its May 13, 2021 guidance stating that vaccinated people don’t need masks or social distancing. Continue reading Post #1188: The CDC finally awakens

Post #1187: COVID-19 trend to 7-26-2021, unchanged

 

Source for the image above is Clipart-library.com, but I’m almost certain that’s a Far Side cartoon, so the real attribution is Copyright Gary Larson, used here without permission.

No change in trend.  New cases continue to increase about 60% per week.  The U.S. is now seeing about 17.5 new COVID-19 cases / 100,000 / day.  Florida and Michigan haven’t reported new data yet, so the trend number might bump up a bit tomorrow. Continue reading Post #1187: COVID-19 trend to 7-26-2021, unchanged