Welcome to another MedCram COVID-19 update. Here's the question that everyone seems to be asking and
that is: which booster should I take? Well in true MedCram form, we're going to look at the data
and make a decision. Recently there's been a study that's come out that has not been published or
peer-reviewed, but is on this pre-print server that was conducted by a number of experienced
researchers out of a number of universities across the country and also in medical schools
across the country, including the NIH, and also major hospital systems like Kaiser-Permanente,
and this study was performed in the United States, and it looks at just that question.
So it takes a look at people who have been vaccinated with Moderna, people who have been
vaccinated with Johnson and Johnson, and people who have been vaccinated with Pfizer, and they waited
about 12 weeks and they randomized them to receive a Moderna booster, a Johnson and Johnson booster, and a
Pfizer booster. In each one of these categories, there were about 50 in each of these groups,
and they split it evenly, so that 25 in each group was less than the age of 55 and 25 were
greater than the age of 55. And as it turns out, there was 154 in the Moderna group, 150 in the
Johnson and Johnson group, and 154 in the Pfizer group. So a total of 458 subjects in this study.
And what these scientists wanted to ask is what was the safety data like for each one of these
categories, and what was the efficacy data like in terms of the ability to mount an antibody response?
Well, let's take a look at the data. So let's look first at the safety data, and what we see here
is we see the cohort that had Johnson and Johnson as the original vaccination,
and then were boosted with the Moderna vaccine, but notice that in this study they used the full dose
Moderna vaccine, because that's what they had available to them. Currently, though, if
you were to go and get a booster shot with the Moderna vaccine you would get the 50 microgram
dose or what is known as the half dose. Be aware of that Moderna is the only one out of these three
that have reduced the dosages for the booster shot . Also notice that there are three different colors
here in terms of the graph. There is the light, which is mild. There is the darker, which is the
amount of moderate reaction, and then there is the darkest which is the most severe. So what
we're going to do is we're going to look back and forth here at the different slides, because
if you have had the Johnson and Johnson vaccine, we want to see how these side effect profiles look. If
you were to have the Moderna vaccin,e if you were to have the Johnson Johnson vaccine as a booster,
or if you were to have the Pfizer vaccine as a booster. So this is what it looks like, here,
if you focus on this first box, is if you were Johnson and Johnson getting the Moderna booster,
and this is what it would look like if you had Johnson and Johnson and gotten
the Johnson and Johnson booster, again as the second shot, you can see that there are
a little bit more severe reactions here under malaise or fatigue and the amount of pain
and tenderness at the local site has gone up just a little bit, which is perfectly normal
and acceptable for a vaccine side effect, and let's also remember that a lot of these symptoms
are the results of the immune response that we're hoping to get with the vaccines in the first place.
And here is the boosting with the Pfizer vaccine. You can see a little bit less
in the way of severity, but still a little bit on the higher side, so not much difference in terms
of which of the three would give you the more side effects. Okay let's concentrate now on those that
got Moderna as their original vaccination and look and see what would happen if they got a booster
with Moderna. You can see here that there is a side effect profile that you can see.
There is more moderate symptoms here as you can see with Moderna what would happen if they got the
Johnson and Johnson as a booster. Here you can see also some moderate side effects, especially in the
headache, myalgia, and fatigue category. What about if Moderna patients got the Pfizer booster? And
you can see here that there seems to be a little bit more mild reaction to those who get the Pfizer
booster who had Moderna originally. Okay let's finally look at those who got the Pfizer vaccine.
In this case, those who got the Pfizer vaccine and get the Moderna boost, you can see that there is
some side effects there in terms of moderate myalgia, malaise, headache, etc. When I say side
effects, I'm referring to the effects that we would expect to have happen if somebody got a vaccine,
but would be considered a negative on the face of it, but something completely expected in this case.
For those who had the Pfizer vaccine and get the Johnson and Johnson booster, you can see
that there's also a little bit higher levels in this area of malaise and headache, but not much
different. And finally those going for their third shot of Pfizer, that would be the Pfizer booster
for those that had Pfizer before, you can see here again a very similar type of profile and
while these symptoms after the vaccine boost were quite frequent, most if not all of them went away
quite shortly after the boost. Now, let's talk about efficacy, and here again we're going to be looking
at very similar types of situations in this graph. e We're looking at the IgG binding to s2pwa1 which
is basically using spike protein as a surrogate for immunity. So in other words, what we're looking
at here is, how well do the antibodies or the IgG that's made after the booster, how well does it
bind the spike protein that we see in SARS-CoV-2? And in this case, it's a surrogate of
the actual viral spike protein, so the higher the numbers here, the better the immune reaction from
the booster shot. And what we're looking at here is looking at the amount of IgG binding on day one, so
that's basically the baseline and you can actually get a lot of information just by looking at all
of these different day ones on all of these different graphs. And so what we have here is
those with the Johnson and Johnson here in the first column getting a Moderna boost, those here
Johnson and Johnson getting a Johnson and Johnson boost, and in the first column Johnson and Johnson
getting a Pfizer boost, but before we go to that, looking at the boost. Let's just take a look at
where things stand. On the first day, you can see here that the antibodies from the Johnson and
Johnson is considerably and consistently lower than the Moderna and or the Pfizer, and this goes
along with what we've seen clinically in terms of prevention of hospitalization. So I do believe
that this surrogate marker is actually predictive of clinical outcomes. So the higher this goes,
potentially, the better protection one would get from getting a booster. Also remember too that this
scale here on the y-axis is logarithmic, so the higher up you go, the bigger the differences are.
Now again, I want you to remember that this is the full dose for Moderna, not the half dose that you
might pick up when you went to go get your actual booster shot. Let's talk about what happened. So
those who get the J and J shot, what happens when they get a Moderna booster? You can see
that there's quite a rise in those antibodies. What happens when J and J gets a J and J booster? Not much
of a rise in comparison to the full dose Moderna. What happens when a Johnson and Johnson gets a Pfizer
booster? You can see there that there is quite a bit of a jump. So I would say for a J and J
person, they should either get the Moderna or the Pfizer booster. What about those that have
Moderna to begin with? You can see here that out of all three, typically the Moderna recipients
have the highest binding antibody levels, so the question is, what happens when they get
a booster of the three different types? A Moderna being boosted by a Moderna does go up even still.
A Moderna going up with a Johnson and Johnson does actually go up, and if you compare
the 29-day in both cases, it's actually not too different. A Moderna however being boosted with a
Pfizer seems to go up even higher than either one, and the reason again why we don't have day 29 data
on the Pfizer boost there on the far right is because this is a preliminary
data release, and that data has not yet come in. So one can make the judgment here that
when you compare this to this one even still a Moderna vaccinated with the Moderna gives you
the highest antibody levels anywhere on this chart. And so it could still be reasonably argued that
even though you've had Moderna before and you're gonna get a booster, it might be best to get
Moderna for a third shot, but again we're still missing this data. We don't know where this is
going to go afterwards. Let's talk about those that have had the Pfizer vaccine. So those that have
the Pfizer vaccine and get the Moderna do go up significantly here. Those that get the Pfizer and
boost with Johnson and Johnson don't seem to go up as much, and those that have the Pfizer and boost
with the Pfizer do seem to go up as much as those with the boost for Moderna. Remember, we don't have
some of this data and also this is full dose that we're testing here, and what's actually available
for a booster is the half dose. Another way of looking at this is looking at the neutralizing
antibody titers in the same situations that we looked at before, and as you can see here
the results were nearly identical to looking at the IgG binding to the spike protein surrogate.
So of note, if we're interested in looking at the efficacy of a booster on top of a fully vaccinated
person, then the question is what does a randomized placebo-controlled trial show and the results of
such a randomized placebo-controlled trial was published as a press release on October 21st
from Pfizer. This has not been peer reviewed or published as yet, but Pfizer's record in
terms of releasing data in press releases has been pretty good, and the numbers have turned out to be
pretty accurate. So because of that, we shared these numbers here, so what they basically did
is they took fully vaccinated patients with two shots of the Pfizer vaccine and there was about 10,000
subjects in this study, which was randomized one to one with a third shot of the Pfizer vaccine
and placebo and the participants in this study were 16 years and older, and remember now that's
a little bit different than what the FDA recently allowed for boosters, but again this is the trials,
the phase three trials, for the booster and in terms of the ages you probably want to know
how many of these were in what age category. What they have told us is that the median age
was 53 years of age and that 23 of the people in this cohort were above the age of 65 years.
Again, they've told us that there were 10,000 in this study, so we're assuming that there were about
5,000 in each arm since it was a one-to-one study and they began looking for symptoms seven days
after the shot. They finally reached the end point in the study with five cases in the intervention
group. The people that got the third shot of the Pfizer vaccine the booster and there were 109
cases of symptomatic COVID in the placebo group. So again we're looking for symptomatic COVID-19.
And because of those cases, they're saying that there was a 95.6 percent efficacy
of the vaccine to prevent symptomatic COVID-19 in patients who have already had
two doses of the Pfizer vaccine. Now I'm going to make some assumptions here that if there were 5000
in both groups and the mean follow-up time was about 2.5 months, which is important to understand,
and that means if they had five cases in 5,000 that would mean that there was a .00
chance of having symptomatic COVID in the intervention group, and about 0.0218
chances of having COVID with just two shots of the Pfizer vaccine. So you can see these are
pretty low. Here you have a one in one thousand chance as the absolute risk, and over here you
have about a two percent absolute risk. So the real key that we need to know in terms of the
value of an intervention is what is the absolute risk reduction? The absolute risk reduction is
simply one minus the other, and in that case the absolute risk reduction is 0.0.
Now you'll know from statistics that if you want to prevent one person from having symptomatic
COVID-19, how many people need to get the booster to prevent one of those people from getting
symptomatic COVID-19? That's known as the number needed to treat or in this case the
number needed to vaccinate and that's simply the reciprocal of the absolute risk reduction,
and in this case that's about 48. And to give you an idea of what this means, to prevent death
in somebody with a stroke TIA or myocardial infarction, giving an aspirin to them daily
given to 67 people, in fact, will prevent one death, and that's a little bit less effective than what
we're seeing here in terms of the number of people that need to get one immunization to prevent one
of these people from getting symptomatic COVID-19 is 48. That's actually not too bad, but remember
of course that it actually could be even better than 48 because the follow-up time here was only
2.5 months, and I think most people agree that the vaccine shots, well we don't know how long
they last, probably last longer than 2.5 months. It'll be interesting to see once this paper
gets published and peer-reviewed what the final conclusions are, but I thought I'd bring this up
in terms of the data out there and what it is looking like. Some might be wondering whether
or not this has a higher effect in those that are older versus younger. Pfizer did say in the
statement that multiple subgroup analysis of the efficacy were performed and there
was no difference of other core morbidities. They also mentioned that the adverse events
were consistent with all of the patterns that had been done before with the initial
vaccination schedule. As always there'll be more data to come and analyze. Thanks for joining us.