A COVID Vaccine Reality Check

[Michael Coston]

A COVID Vaccine Reality Check


HHS Sample Framework For Vaccine Distribution


#15,524

While I am a decidedly pro-vaccine blogger - one who gets a flu shot every year and has plans to get the shingles vaccine in the next few months - I am also a vaccine realist, and I wince a little every time an as-yet unproven COVID-19 vaccine is trotted out as being the panacea for our current pandemic.

The average American (and for that matter, global citizen) has been led to believe - by politicians, the media, and `Forward Looking' & `Aspirational' Vaccine Press Releases - that a safe and effective COVID-19 vaccine is `just around the corner', and that once that happens life will return to `normal'.

But of course, it's not going to be that simple, even assuming that one or more COVID vaccines receive EUA (Emergency Use Authorization) by the end of the year.

Left out (or glossed over) has been the reality that in the opening months of 2021, vaccine quantities will be quite limited and some groups (i.e. children, pregnant women) - who have not (as yet) been part of vaccine safety trials - may not be offered the vaccine at all (see CDC: 10 Things Healthcare Professionals Need to Know about U.S. COVID-19 Vaccination Plans).

Vaccine recipients will likely need two shots, spaced roughly 28 days apart, which will further decrease the number of people that can be immunized early on. The logistics of how a vaccine will be dispensed, and who will be prioritized to get it first (HCWs, 1st Responders, the Elderly?), have not yet been announced.

As we've discussed previously (see Remembering An Emergency Pandemic Vaccine Program That Went Awry), mounting a nationwide emergency vaccination campaign is a massive undertaking, and one that could easily be derailed by bad publicity or vaccine hesitancy.

While the safety of any new vaccine will be paramount, and we ought to have reasonable data on that (at least for cohorts involved in the safety trials), we may know very little about the effectiveness of any experimental vaccine at the start.

It normally takes a couple of years (at least) to assess the effectiveness of a new vaccine, and while the UK Has Approved Human COVID-19 Vaccine Challenge Studies, it will be limited in size, only conducted on young and healthy adults (age 18-30), and the results probably won't be published until May of 2021.

While this study could provide important data, how well it will apply to more `at risk' cohorts is unknown. The immune response mounted by 18-30 y.o. healthy adults to the flu vaccine is usually substantially greater than by those over 65.


At this point - even assuming a COVID-19 vaccine can be produced - no one can predict how effective it will be in preventing infection, or lowering the severity of illness, in any age group or demographic. Nor do we know how long any protection from the vaccine will last.

Admittedly, even a vaccine that is only 50% effective in preventing infection, or even one that substantially reduces the odds of developing severe disease, would be an important tool in fighting this pandemic.

But most people expect more from a vaccine, particularly given how much hype this one has received. A modest success could easily appear as a massive failure to most Americans, who are being primed to expect a `magic bullet' against COVID-19.

While most reputable scientists have been careful not to over promise on a COVID vaccine, many have said they are `hopeful' that a safe and effective vaccine can be ready by the end of the year. Left largely unsaid, however, are 1) at what quantity and for who 2) and what constitutes `effective'.

While instilling hope is important, these are the types of omissions that tend to come back and bite us in the behind.

I've always believed it is better to under-promise and over-deliver, than the other way around. Things happen, plans go astray, and sometimes the wheels fall off. The more you promise, the less tolerance there will be for failure.

All of which brings us to an article by Liz Szabo and JoNel Aleccia - published by Kaiser Health News & NBC news - that quotes Dr. William Schaffner, Dr. Peter Lurie, Dr. Arnold Monto, and others on the public's unreasonable expectations for the first generation of COVID-19 vaccines.

Due to its length, I've only posted the link, so click it to read this article in its entirety. I'll have a brief postscript when you return.

COVID-19

Scientists Warn Americans Are Expecting Too Much From a Vaccine

By Liz Szabo and JoNel Aleccia

For some past blogs on the challenges of pandemic vaccine creation, manufacturing, and deployment you may wish to revisit:

WHO: Candidate Vaccines For Pandemic Preparedness - Oct 2020

MRC Report #33: Modelling The Allocation & Impact of a COVID-19 Vaccine

Manufacturing Pandemic Flu Vaccines: Easier Said Than Done

GAO: A Herd Immunity For COVID-19 Primer

https://afludiary.blogspot.com/2020/...ity-check.html

[longshots]

I have been reading FluTrackers and Avian Flu Diary for years and directed family and friends to both many times. As always the above is another great blog entry that deserves widespread distribution. I urge everyone to nudge your family and friends to read specifically the above post, and more generally to follow flutrackers.com and afludiary.blogspot.com

[JJackson]

As longshots points out we need to a dose of realism when accessing what to expect from a vaccine. The current evidence, from natural infection which normally produces the best level of protection, is that most seroconvert but that IgG levels are dependent on disease severity and fall over time. The acute phase generates B & T cells that are specific to SARS-2 and these B cells produce the wanted antibodies. After the illness is cured most of these cells will die off and a few remain. The antibodies produced have a half-life of about 20 days and will also disappear. After this has all occurred the remaining protection is initially from the low level of antibodies continuously produced by those few remaining memory B cells but the memory T cells should pick up any new challenge quickly and produce a lot more disease specific B cell producing well targeted antibodies in volume. This is what we want the vaccine to do.

Given the above the important, and as yet unanswered, question is what level of protection is needed for immunity to infection, immunity to disease or immunity to severe disease. The implications of these three possibilities is in the first you do not get ill nor are you capable of infecting anyone, the second you are an asymptomatic carrier and the in the third case you get a cold or flu like illness. Based on no evidence I would guess you will pass through all three stages you may remain immune for several months then you will slowly pass through the other stages possibly being back to nothing after 10 years. This will require regular booster shots for the foreseeable future.

I have a small quibble with Mike's post, and even that seem churlish given their consistent excellence. I relates to the order in which to expect answers from the vaccine trials. The first answer I would expect is 'is it producing anti-bodies, neutralising antibodies and B & T cells as you might see them in a natural infection?'. The answer seems to be yes from the trials that have got to that stage. Next we will get some hint about how much protection we get. The trials have a small team of experts who can unblind the trial if there is a severe adverse reaction and at set predetermined points in the trial. The first of these will be when there have been a few hundred infections which may show all of them in the placebo arm and none in the vaccinees. If the data is sufficiently clear cut they must unblind the trial and offer all placebo participants the vaccine, if less clear cut they can wait until the numbers are significant. If the initial high antiviral titers show a clear benefit, which I think they will, we will get quick answers. What it, or the natural infection, cannot tell us quickly is how long it will last - a problem for next year. The problem I see with this scenario is we have some safety data from the phase 1 & 2 trials which showed no major problems but then you get the less common side effects. Guillen-barre syndrome has a 1:100,000 appearance in the flu vaccine and the polio vaccine causes paralysis in 1 in million, neither of which are likely to show up even in a 30,000 person trial. There may be others with a higher probability, or that take time to show symptoms, that would only appear very late in the trial or after a 2 year follow-up of trial vaccinees - this is why vaccines do not normally get released until after the results of the post-trial analysis are peer reviewed and published. In short comprehensive safety data will take a long time but the pressure to release widely may be very strong long before the trial is due to end. Another difference this time is under normal circumstance a company would not start mass production until certification but we already have hundreds of thousands of doses ready to go which could be in someone’s arm long before the trial period is due to finish.
The FDA trials have disease reduction as their end point criteria, not sterilising immunity, and the bar has been set at 50% i.e. half the patients in the vaccinated arm must show better outcomes than the placebo arm.