Welcome to another MedCram COVID-19 update.
Daily new cases in the United States seem to be slowly decreasing,
if we look at the seven day moving average,
and the daily new deaths in the United States also seems to be
slowly decreasing, especially if we look at the seven-day moving average, although
it seems to have flattened and then decreased slightly.
If we look at the current toolbox
that we have for COVID-19, we've got, arguably,
four items, amongst many others. Remember that Remdesivir was given
emergency-use authorization from the FDA based on a study that
showed that the time to recovery was reduced
in that randomized controlled trial. It did not show a mortality benefit,
but many people believe that
if the study was taken out to its conclusion -- in other words,
if a thousand people as was planned was enrolled in the study -- that that would
have met statistical significance. Nevertheless, it didn't happen.
There's been some news regarding that,
in that it's been broadened in its scope. More news on that later in this update.
The second one was dexamethasone, and they used it for about 10 days
in the study. This came out of the
RECOVERY trial in Great Britain, and in this case, there actually was a
survival benefit, and in this case, it was six milligrams,
either orally or intravenously, in these patients.
Now, I've been at the bedside taking care of these
patients on a regular basis and there's a number of these patients
that get better very quickly and are able to go home after about four
or five days or even a week. And we found that these patients who
would benefit from dexamethasone are the patients that are on oxygen,
very similar to the initial type of patients that were
requiring Remdesivir, so for Remdesivir, we would give these patients
Remdesivir, if they were requiring supplemental oxygen.
Same thing in the recovery trial, regarding dexamethasone. So these
patients will come in, they would require oxygen, we would start them on
dexamethasone, and we would give it for 10 days.
Why? Because that's exactly the length of time that they used in the recovery trial.
But there were some patients that didn't
get better. In fact, there's a lot of patients that stick around in
the intensive care unit for days, even weeks, if you can believe it.
Those of you out there that are
listening to me that take care of COVID-19 patients know exactly what I'm
talking about. There's a subset of patients: they get
bad, they get worse, they get on the ventilator, and they stay there
for, in some cases, weeks. Well, one of the things that I've noticed
is that when we start these patients on 10 days of dexamethasone,
there is an improvement in not only the clinical
scenario, but also in a number of the blood tests that we check.
So, what are those things that we check? One of those things that we check is a CRP.
CRP stands for c-reactive protein and it is a marker of inflammation going
on in the body, and typically we see that these CRP
levels are very elevated initially, and then when we start them on dexamethasone,
then they start to come down, showing a response.
We see a very similar picture for patients with ferritin.
Now, I know that ferritin has iron as opposed to CRP, and some people
may think that that ferritin may actually work into the pathophysiology.
I know there was some argument about that a few months ago
that iron seemed to be the reason why patients were getting sick.
No, in fact, ferritin is also an acute phase protein and it's going to go up if
there is inflammation going on. And again typically these patients have high
ferritin levels and when you start them on decadron,
it goes down. Number three is the LDH. This is also seen. We see
LDH, which is an intracellular enzyme and when cells are being broken down and
there's inflammation, we see LDH increase as well.
Another one that we keep track of in these patients is a d-dimer.
Now d-dimers are little pieces of protein that is usually the byproduct of
coagulation, and so this is a very rough way of determining if there is
coagulation occurring in the human body, and so we
would typically see these levels up, because we know that there is an
increased risk of thrombosis in COVID-19 patients,
but we don't yet know whether or not this is the be-all and end-all of
coagulation In other words, some groups have put forward some
evidence that would seem to indicate that the d-dimer
isn't capturing everything. That may be the case, but nevertheless,
in all of these situations, we see a pattern of high CRP,
high ferritin, high LDH, and elevated d-dimer in these patients,
and I'm sure you could add other factors in here as well, but in
those patients where we're checking these on a daily basis, we can track
their inflammatory pattern. And when these patients get put on dexamethasone,
which is a corticosteroid, we see that these numbers go down. They
respond to the decadron. The problem is that
these patients, these subset of patients that end up in
the hospital for days, even weeks, At some point, when we put
this order in for dexamethasone to go for 10 days, what
I've noticed anecdotally in a number of patients is
that at the 10th day, the dexamethasone stops, and because
dexamethasone has a fairly long half-life, it's not tapered
off, because when you stop the medication, it eventually wears off after a couple
of days. If you look back at the recovery trial,
they specifically didn't taper the dexamethasone,
but what I've invariably noticed in the patients that I've taken care of is that
these markers start to go back up again. and it's not
just numbers, it's not just we're looking at
the LDH and the d-dimer. I'm also starting to see clinical
evidence of deterioration after about 10 days, and then stopping
the dexamethasone and seeing these factors go back up
again. What I'll also see as an evidence of
that is that the FIO2, which is the amount of oxygen that we
have to give these patients, also starts to go up, and I've seen these
anecdotally in a number of patients to the point where
I've made a mental note of that, and I'm very careful now
at the end of 10 days to determine: is this patient going to benefit from
stopping? I stop it and I watch very carefully,
specifically looking at these numbers again. This is anecdotal evidence. I don't
know whether or not there's a sub-section of patients that may do
better with a longer course, but I think it needs to be looked into,
and this also brings up a wider point, which is:
yeah, we know what medications in our toolbox are helpful against COVID-19,
but the real science and the real art of taking care of patients in the intensive
care unit is paying attention to detail, looking at
all of those regular things that we look at in every
patient who's in the intensive care unit. We look at their sodium concentration;
we look at their potassium concentration; we look at their acid-base status,
something that we call a chem-7, it looks like a little kind of a fish bone type
of structure on a paper where we look at their sodium,
their potassium, their chloride, their bicarbonate concentration, which is
listed as CO2; we look at their BUN; and we look at
their creatinine, basically their kidney function,
and their glucose, to give you an example, when a patient is on the ventilator with
COVID-19. They're breathing rapidly in some cases.
We have the ventilator set to 20 or 30 breaths per minute, and because of
that they're breathing out a lot of moisture.
Well that's a lot of free water loss, and so if you don't replace
that, you're not careful, the total body concentration of just
about everything, including the sodium, will start to rise -- and you'll see this
imperceptibly on a daily basis -- that if this patient is
being dehydrated and not being replaced with free water, you'll start to see a
sodium concentration, which is normally around 140 to 145,
go as high as 150 or even higher. And so what you need to do is to be able to,
first of all, pick this up and to be able to replace that free water, otherwise the
patients could be very uncomfortable and you could start getting dehydration
and worsening kidney function. And so because this diligent attention
to detail in the intensive care unit is so
important, we've put together a course on monitoring this chem-7 and
it's going to be premiering very shortly on our
MedCram.com platform. And this is intended for healthcare
providers who are taking care of patients in the outpatient setting,
in the inpatient setting, and in the intensive care unit. How fast should you
correct sodium? What are the correct medications for
bringing down potassium? What is the meaning of a low or high
bicarbonate level? And what does it mean if there's an
anion gap? What about the bun? What happens if it's low? What happens if
it's high? How does the liver affect that? What about creatinine?
Are there medications that can increase the creatinine without actually changing
the renal function? And then, what do you do about glucose?
What happens if it's low? How do you keep it from being too high?
All of these things are important and get mixed in to the survival benefit
in these patients with COVID-19, because as we've just discussed, a lot of these
patients hang around in the intensive care unit for days
and even weeks. Moving on really quickly, we've talked about plasma. We do have
data on plasma, but it's not placebo-controlled, it's not a controlled
trial, and so more work still needs to be done
on that, but there was also another emergency use
authorization by the FDA to allow us to use plasma
in COVID-19 patients, and so that has continued and we are continuing to use
plasma. And of course testing, now we've talked
about testing before, what about those paper tests? Okay, not
for use in the hospital particularly, but especially now that schools are
opening, in some cases, and we want to be able to identify
people with the disease, specifically who can
transmit it, who are infectious, who are contagious, and the
sensitivity on those type of tests need not be at
the level that we have currently for our
diagnostic tests that are in the hospital, and I want to
say, look out for another interview that we're going to
have with Dr. Michael Minna on this topic. Last time we talked to you
about three patients that have been reinfected, and in most of these cases, in
fact in all three of these cases, the second infection was deemed to be
more mild or even asymptomatic. In fact, in one of the cases the patient only
knew that he had the COVID-19, or coronavirus,
the second time because of a screening evaluation
that he did when he flew back from Europe to
Hong Kong. We now report a 25-year-old from Nevada. So this is the
first American case that we have of this, where in mid-April, the patient
came down with symptoms of headache, cough, sore throat,
nausea, and diarrhea, but after about 10 days, his symptoms
completely went away. Then, at the end of May, after
testing negative times two to the virus, the patient developed
these symptoms: headache, fever, and, again, nausea and diarrhea.
The patient tested positive, so he tested positive
here at the first case, then tested negative times two
before testing positive again. And when they compared the genomes
of these two positivities they found that
they were different. There was a number of differences
in the RNA or the genomic material of these viruses. Both of them,
however, were SARS-CoV-2. The difference though, in this case,
was that the patient actually had to be hospitalized the second time
and required oxygen but not a ventilator.
And here's the actual preprint. It has not been peer-reviewed as yet,
but we will put the link in the description below, and
here they have the abstract and the full paper. You may have to sign up to the
site to be able to read. Of course, it's unclear how generalizable
these findings are, or whether this will affect
the efficacy of vaccines, which we'll talk about later in this update.
One of the things that we mentioned earlier in this update was the use of
Remdesisvir in patients with COVID-19. N
Now, until August 28, 2020, Remdesivir was indicated for the use of COVID-19 in
patients who required supplemental oxygen, and
they discouraged the use of Remdesivir in patients with low
renal function and also with patients with high liver
function tests or elevated liver enzymes. On
August 28th, however, they broadened that indication in a emergency use
authorization for all hospitalized patients who are positive for SARS-CoV-2
and have COVID-19. So in other words, you don't have to be
on supplemental oxygen. And this is the press release,
and we'll put a link in the description below. Remember that Remdesivir is
an intravenous medication, and so it will be
difficult to give this to patients in the outpatient setting
unless something is done to change the vehicle in which it is
administered. I also wanted to report that while
Moderna and Pfizer have already initiated phase
three trials of their vaccine, Tuesday will mark the third company
Astrazeneca in combination with Oxford University
in the UK to start their phase three trials,
and all three of those companies are looking for about thirty
thousand subjects to populate their phase three trials,
and they're hoping to get some data out at least from this
oxford COVID-19 vaccine by Thanksgiving. For those of you who don't know
Thanksgiving in the United States is around the end of November and also
to remind you about the Oxford study, what they're doing is they're taking an
adenovirus vehicle and they are changing the
genetics of that adenovirus so that it presents to the host, to the person
getting the vaccine, the protein for the spike protein on the
coronavirus itself, so that antibodies are made
against that spike protein, and just to remind you about this particular Oxford
coronavirus vaccine, there was a story that was published in
the Oxford Vaccine Group that showed on July
20, 2020 that there was a strong response
to this vaccine, and I'll quote here, "The results of a phase
I/II trial published today in the scientific journal, The Lancet,
indicate no early safety concerns, and it induces a strong
immune response in both parts of the immune system.
The vaccine provoked a t-cell response within 14 days of vaccination,
and also an antibody response within 28 days."
And the chief investigator professor, Andrew Pollard
at the Oxford Vaccine Trial at Oxford University says,
"We saw the strongest immune response in the 10 participants who received two
doses of the vaccine, indicating that this might be a good
strategy for vaccination." And a little bit more about
that phase III trial, they said here that Oxford and
Astrazeneca are collaborating with clinical partners
around the world as part of a global clinical program to trial the Oxford
vaccine. The global program is made up of a phase
III trial in the U.S., enrolling 30,000 patients, a pediatric study as
well as a phase III trial to low- to middle- income
countries, including Brazil and South Africa,
which are already underway. So this does look promising, and we'll have to see
what those results will be later this year. And hopefully
we'll have something to be thankful for at Thanksgiving, and I just wanted to
add that neither I nor anybody else here at
MedCram have any financial ties to Oxford or to
Astrazeneca, or for any other vaccine producer for that matter.
What we do have an interest in is seeing this COVID-19
disease licked, and for that, we will keep working toward an ends.
Don't forget to check out our medical- related lectures
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classroom style, perfectly designed for the COVID-19
epidemic. If you are an institution interested in
such courses, please contact us at MedCram.com. Thanks for joining us!