Welcome to another MedCram COVID-19 update. In the previous video, we talked about the efficacy
of the vaccines against the delta variant, but there's been a lot of questions about whether
or not natural immunity is sufficient for the delta variant. If you've had COVID-19 in the past,
does that natural immunity protect you from getting COVID-19 in the future, and
does the delta variant change the equation on that? Let's talk about what the data shows.
So for a great real world example, we turn to this paper that has not been peer reviewed
or published yet, but it was a study involving over 50,000 subjects at the Cleveland Clinic.
On December 16th, what the Cleveland Clinic was able to do, based on their subjects, 52,238,
was they were able to determine that 2,579 of them, before the campaign of vaccination started,
were already infected with SARS-CoV-2, and that 49,659 were not infected with SARS-CoV-2. Then what
they did was they tracked them over the next five months, and they saw those that were vaccinated and
those that were not vaccinated, and the question was in a comparison, specifically looking very
carefully at those that were infected and not vaccinated. So in other words, these people here,
how did they do in comparison to those that were infected but vaccinated? In other words, was there
a difference in the incidence of new COVID-19 between these two groups? So what we're seeing here
on the x-axis is five months of time. So 30 days times five months is 150 days, and it starts here
at time zero when they began vaccinations. And as you can see here, all of the groups except for one
had no accumulation of incidents of COVID-19 in the not previously infected vaccinated group.
In the previously infected but unvaccinated group and in the previously infected vaccinated group,
however, there was one group that did accumulate COVID-19 infections as time
went on, and that was the not previously infected and unvaccinated group as seen here on the y-axis,
which is basically showing what percent of the cohort became positive. You have one percent,
two percent, three percent, four percent, and of course, that's growing with time. So in other words,
by 30 days in, 3 percent of the not previously infected and unvaccinated group had turned positive for
COVID-19. Now that's in contradistinction to the previously infected but unvaccinated group.
They behaved very similarly to the vaccinated group, indicating that previous infection was just
as good in real world data as being vaccinated. And I just want to stress again that this data
was collected before the delta variant. Another interesting article appeared in JAMA, titled
"Associations of vaccination and of prior infection with positive PCR test results for SARS-CoV-2
in airline passengers arriving in Qatar." So what they did was they initiated a program looking at
passengers arriving at Hamad International Airport, and they actually had about 261,000 subjects in
the study, so it was a big study, and what they did was they divided into three groups. The first
group was those that were vaccinated and could show documentation of vaccination. There was 31,190
subjects in that group. Then, the other group was those that were not vaccinated,
but had evidence of previously being infected, and that was 9,180. And then, they looked at the
group that was not vaccinated and did not have a past history of infection, and that one was 215,901.
And then, they looked at the positivity rate. Yes, they had everybody take a SARS-CoV-2 test for
positivity to see whether or not they were positive, and if you were to look at this in
just some round numbers, the positivity rate on the vaccinated group was 0.82 percent.
And that's not surprising that it would be that low, because these people were all vaccinated.
However, when you looked at those that were not vaccinated and had not had a history of
infection, their infectivity rate was about 3.8 percent. So the question is: what would these
people who were previously infected look like even though they had no evidence of vaccination? Would
it be closer to these people here that were not vaccinated and never infected, or closer to these
people who were previously infected? In other words, were they getting a benefit from having a previous
infection in reducing their rate of testing positive at the airport? And the answer to that was
the positivity rate was about 1.0 so very close to the 0.82 and further away from the 3.8. Again,
lending credence to the idea that previous natural infection of SARS-CoV-2 gives you some immunity
against being re-infected. Again, strength of this study shows in the size and the number of subjects
in the study and the one drawback of this study, in terms of predicting outcomes in a delta variant
world, is that this data was collected between February 18 and April 26, 2021, before the delta
variant was an issue. Another great release of study is this from the United Kingdom's government,
titled "New national surveillance of possible COVID-19 re-infection," published by Public Health
England. Subtitle is that "New data suggests a low risk of COVID-19 reinfection in the population." And
this was just released in June of 2021. So what they found was that there was 15,893 possible
re-infections, but, remember, the denominator here is out of 4 million people with confirmed cases.
When they looked at it more closely, for the data, that was narrowed down to about 478
probable infections and about 53 confirmed reinfections, and this of course led them to say,
"The current data shows that there is a low risk of infection with SARS-CoV-2. There were 15,893
possible reinfections with SARS-CoV-2 identified up to the 30 May 2021 in England throughout
the pandemic, out of nearly 4 million people with confirmed infections. This is equivalent to around
0.4? cases becoming reinfected." So the risk of re-infection up to this point is extremely low.
So currently we do have not only biochemical data with antibodies, but we also have real world data
in terms of the strength of natural immunity for the prevention of COVID-19. However, all
of that data in terms of real world data is cast unfortunately in the pre-delta world. The question
is: what does the delta variant do in terms of changing the paradigm that natural immunity
seems to be effective in real world data. Well, enter in this paper that was published in Nature
and accepted on the 29th of June 2021, titled "Reduced sensitivity of SARS-CoV-2 variant Delta
to antibody neutralization." And what we're looking here again is a surrogate for immunity in terms of
the response. Now, it's not just any surrogate, because what we're interested in here is the
ability of antibodies to neutralize the spike protein. Now, we realize that there are other
aspects of the immune system that is important in neutralizing a virus. As we've talked about
many times here on MedCram, there is the innate immune system, but then there's also the adaptive
immune system, and there are T cells, and there are a whole host of other aspects to the immune system.
So we're just looking at one aspect, but it's an important aspect, because, remember,
notwithstanding the T cell responses and all of the other things that are involved with what a
vaccine does to the immune system, one of the main purposes of the vaccine in terms of preventing
infection is to make antibodies against the virus, so measuring antibody response, while a surrogate,
is important. So let's break down the information here. This was a cohort from Strasbourg, Germany (correction: Strasbourg, France),
where they had 26 subjects that were previously infected with SARS-CoV-2, and they took their
convalescent sera, which basically means they took their antibodies 12 months after the onset
of symptoms, and what they did was they measured the efficacy of their ability to bind the virus.
And they measured it out here on this graph. Now, I looked at four different types, or four
different variants, of the virus: the D614G, which is an older variant, the Alpha, which is the UK variant,
the Beta, which is the South African variant, and, of course, the Delta variant, which we're talking about
in this video. And how they measured efficacy was by looking at something called the ED50.
Now the ED50 is the effective dose at which the antibodies are able to neutralize 50 percent of
the virus, and so what you want here is the average response, or the average dose, which is marked here
in this dark black line. You want this to be high. That means that the effective dose is quite high,
given the sera from the patient, which are these antibodies. And so as you can clearly see here,
whereas the alpha variant, or the UK variant, the effective dose from these subjects was high. For
the beta and delta, it was low. Now, we're concerned about delta here, and not so much beta, because
delta is far more infectious than the beta variant. Now from that same cohort, they were able to take
subjects again that had previously been infected with SARS-CoV-2, and in this case, they looked at
the response to these subjects after one dose of a vaccine. And in this case, the cohort included nine
subjects who had the AstraZeneca vaccine, one dose, nine subjects who had the Pfizer vaccine, one dose,
and three subjects that had the Moderna vaccine , one dose. And you can see here what just one dose
of any of those vaccines did to the effective dose in these subjects for these given variants.
And just in case you were wondering, these dotted lines is the lower limit of detection
for this study. Now in another cohort, this time in Orleans, France, they looked at the
same thing, except in this time, they looked at the patients week three after the first
dose of vaccination. And, as you know, for Pfizer, you get your second dose
three weeks later. And so, essentially, what they're doing is they're looking at the antibody levels
right before the second dose. And here's something that's very interesting: what we're looking at
here is, again, these variants, the D614G, the alpha, the beta, and the delta, and what you can see here
is that after one dose of the Pfizer vaccine, we're looking at very low levels of protection
for the delta variant, very low, arguably lower than the natural infection levels of antibody that
you would see in the cohort that we saw here in Strasbourg, Germany (France). However, after the second dose
of the Pfizer vaccine, so now we're looking at eight weeks after vaccination, or week
five after the second dose, you can see that these levels have actually come up pretty substantially.
They also did this similarly with the AstraZeneca vaccine, and you can see very similar pictures here.
So what i'm going to do here is zoom out a little bit so you can compare
the question regarding the delta variant in terms of the surrogate marker of effective dose
of antibodies from convalescent plasma. If you compare someone who has been infected with the
virus in the past, this is the type of effective dose that the antibodies from that type of patient
is going to have against the delta variant, as opposed to somebody who's been previously
infected and got one dose of the vaccine versus somebody who has not gotten the infection in the
past and has gotten two doses of the vaccine. And so you can clearly see here that the best
case scenario for those people who have had the virus in the past is to get at least one dose
of the vaccine, based on this data, and for those that have not been infected, to get definitely
two doses of the vaccine, if it's a Pfizer one in this case or AstraZeneca. Probably the worst case
scenario, of course, is no vaccination and never have been infected. But just above that is just
getting one dose of the vaccine based on this data. The other thing that this article showed
is that monoclonal antibodies that have been commercially available for patients with severe
COVID-19 but not yet requiring oxygen, for instance, Bamlanivimab, were not very effective
against neutralizing the delta variant, and, of course, that's a problem, because that was one of
the tools that we had in the previous wave to help those patients that were early on in the infection
but did not want to progress to hospitalization. The authors go on to say, "we further show that
delta is less sensitive to sera from naturally immunized individuals. Vaccination of convalescent
individuals boosted the humoral immune response well above the threshold of neutralization.
These results strongly suggest that vaccination of previously infected individuals will be
most likely protective against a large array of circulating viral strains, including variant Delta."
And so because of that study that was published in Nature, there has been a call that patients
who are getting the two-dose vaccination from either Pfizer-BioNTech or Moderna need to make
sure that they get that second dose, especially in a situation like we are in now where the Delta
variant is becoming more and more prolific. And this is the most likely reason why we are starting
to see surges in COVID-19 hospitalizations in the midwest, and for those providers on
the front line, O want to remind you that we have a library of very useful videos in taking care
of COVID-19 patients, whether it's learning about ventilators or relearning EKGS. I want to highlight
this lung ultrasound MedCram video, hosted by Dr. Joshua Jaquet, who is actually from the Cleveland
Clinic and is one of our faculty here at MedCram. If you want to improve your diagnostic skills and
the speed at which you come up with diagnoses in terms of COVID-19 and the lungs, probably nothing
will do that faster for you than an understanding in lung ultrasound, because CT scans are difficult
to use, because of the cleaning that has to happen after each patient while the ultrasound probe
has to be clean. It's much easier to do, it's much more portable, it gives you real-time information,
and it can be very helpful, especially in analyzing the lung. So I invite you to brush up on your lung
ultrasound, especially with the possibility of another surge here in the United States
and around the world. And for more videos, visit us at MedCram.com. Thanks for joining us.