Welcome to another MedCram COVID-19 update.
And in the United States, we continue to have this interesting situation where the daily
new cases in the United States continue to rise, but the daily deaths are only rising
minimally.
Now of course, that's diverse across the country.
For instance, in Utah, daily new cases are definitely on the surge, and daily deaths
are not commensurate with that.
In California, daily new cases have actually plateaued somewhat, and daily new deaths are
not on the rise.
It's been 11 days since Hawaii opened up and opted out of the 14-day quarantine so long
as there was a negative COVID-19 test.
Daily deaths in Hawaii are also not on the increase.
So today I want to talk about immunity, and in two facets: we'll talk about convalescent
plasma and we'll also talk about what's latest with the vaccine.
So let's first talk about convalescent plasma, and as you know convalescent plasma is currently
FDA approved, using and emergency-use authorization to be used in COVID-19.
Well there's the results of a fairly large trial that's just come out of India and published
in the British Medical Journal on convalescent plasma.
And this is know as the PLACID trial, and of course we will put the link to this article
in the description below.
And this was a multi-centered study that looked at 39 public and private hospitals across
India.
Patients had to be at least 18 years of age.
So in this study, they took 464 patients and they randomized them to either receive convalescent
plasma or placebo.
Now in this case the convalescent plasma was 200 mL, and they did it twice, 24 hours apart.
It was randomized, and as it turns out 235 received the convalescent plasma and 229 did
not.
When they looked at these patients, the patients that were enrolled, something called a PF
ratio.
P being the amount of oxygen and the F being the amount of oxygen that had to be given.
So people with PF ratios that are higher are people that are less sick.
So, in this case, patients to be enrolled in the study have to have a PF ratio of 2
to 3 hundred.
Now, normal is around 4 to 5 hundred.
So these people were somewhat impaired.
Now the endpoints were to either have a PF ratio of worsening, which would be around
100, or death.
And that was the endpoint.
And they wanted to see how many of these patients here and here actually went to the PF ratio
of 100, which would be worse, or death.
And at the end of the study, what they found was that those that got convalescent plasma
had a 19% chance of reaching one of these two endpoints, and those in the placebo arm
had an 18% chance.
So it was actually lower in the placebo group, but the difference between 18 and 19 percent
in this case was not statistically significant.
And so they concluded that there was no difference in these patients: those who got convalescent
plasma versus those that did not.
Now there was an editorial that went along with the publication in this British Medical
Journal and it was interesting to know what was mentioned here in this specific article.
They did note that small beneficial effects were found for resolution of shortness of
breath and fatigue.
However, these results should be interpreted with caution, because the trial was not blinded,
so knowledge of treatment status could have influenced the reporting of subjective symptoms
by patients who survived to day 7.
The other interesting thing that they mentioned was that the primary hypothesized mechanism
of benefit from convalescent plasma is through direct antiviral action of neutralizing antibodies
on SARS-CoV-2 RNA.
In this trial, the statistically significant 20% higher rate of conversion to a negative
result for SARS-CoV-2 RNA occurred on day 7 among patients in the intervention arm.
So, in other words, the antibodies did what they were supposed to do.
And they mention that here.
Yet, there was no net clinical benefit to patients.
Why might this be the case?
The next thing that they do is they describe the fact that when you give plasma, you can
actually make the patient more hyper-coagulable, and that's exactly the problem that we have
in COVID-19.
And so it very well could be that while the plasma is neutralizing the virus, it may be
making the thrombotic nature of COVID-19 worse.
And it looks like in this case, they left it up to the physicians to determine whether
or not the complication was related to the plasma.
And they may not have recognized that if there was a thrombotic event.
They also bring up some interesting points that I believe are pretty important, and you
can read some of those here in the editorial.
So there's actually a counterbalance issue with convalescent plasma.
Convalescent plasma, on one hand, has antibodies that will neutralize SARS-CoV-2, but on the
other hand, convalescent plasma also has clotting factors.
And that can exacerbate the already increased tendency to clot in COVID-19, and as you can
see here in the article it says that immunoglobulin therapy, which is derived from whole plasma,
is subject to a U.S. Food and Drug Administration warning about the risks of thrombosis, particularly
in older patients, those with cardiovascular risk factors, and those with hypercoagulable
conditions.
Wouldn't it be great to be able to have the benefits of immunoglobulins without the side
effects of the clotting factors?
Well, that's exactly what you would get with monoclonal antibodies.
Monoclonal antibodies typically are synthetic antibodies that are produced and purified
and given in isolation from these other thrombotic agents.
So far, trials are underway testing out those monoclonal antibodies are more data is going
to be forthcoming.
And what else is gonna be forthcoming are the results on these vaccine trials, which
are getting towards a foreseeable end here.
The vaccine candidate from AstraZeneca and Johnson & Johnson have both started enrollment
in the United States, after they were both briefly stopped because of some safety investigations
that turned out to show that the concerns were not related to the vaccine.
And, of course, in trials of this magnitude, 30-60,000 people bring enrolled in these studies,
you're bound to have some things happening that is going to cause people to look and
make sure that the vaccine isn't causing problems.
And as we go forward, we at MedCram are going to do a deep dive on these vaccines and give
you some information, so that you'll be able to understand as these results come out and
make decisions.
Currently, we don't know data in terms of efficacy or safety, and so when they do come
out, we'll need to have a context to put those in, and that's where we're going to help out.
So watch for that in the future.
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