welcome to another MedCram COVID-19 update I want to focus a little bit on
the United States for the particular reason that there are a number of states
and counties that are quote opening up it seems as though some of the rural
areas are just starting to increase so I want to look at some states in terms of
deaths per 1 million population New York is still at the top followed by New
Jersey Connecticut Massachusetts New York is also near the top here in terms
of tests per million population in terms of states that have the least amount of
deaths per million population we're looking at Hawaii Wyoming Alaska Montana
these are generally rural areas but even when you start looking at them on a per
capita basis they have the lowest death rates going back to the deaths per
million population when you look at the West Coast like a state like California
they're actually below average in terms of the average for the United States
which is 252 deaths per million in California is at 73 the state that's
done the most amount of tests per capita is Rhode Island and the state that's
done the least amount of tests per capita is the state of Maine in
California where things are supposed to be opening up soon at least slowly
through phases were not really seeing a reduction here in the daily new cases
nor are we seeing really a reduction in the daily deaths okay let's take a look
at Russia we were reporting earlier that there had been a dramatic increase in
cases that seems to have leveled off at least according to these numbers
fortunately in Spain we're seeing a reduction in the number of cases there
we're starting to see in the news media that people are picking up on this idea
that kovat 19 is not just a respiratory disease but in fact it's affecting a lot
of other parts of the body and as many of you know we've discussed this issue
with regards to the triple hit on oxidative stress
from this virus and that's opened up a whole discussion about the body's
defense mechanisms with respect to antioxidants one of those that we
highlighted last time was glutathione peroxidase enzyme which takes
glutathione and oxidizes it in the process of reducing hydrogen peroxide
back to water and this brought about the whole discussion with regards to an acid
teal cysteine in its way of recharging glutathione and improving oxidative
stress in some of these respiratory illnesses and for a full comprehensive
review of that I recommend that you look at update 69 one of the important things
that we talked about was glutathione and if you don't know glutathione is
actually three amino acids put together the middle one is cysteine and it's
right here it's the part that holds this SH group which we talked about last time
which is a reducing agent on this side over here we have glycine and on this
side over here we have glutamate but glutamate is not attached to the
normalcy that it would normally be attached to in a polypeptide chain it's
actually attached to the gamma carboxylic group which is down here but
nevertheless there are three amino acids which make up glutathione the other part
that I want you to know is that this part right here which is the glycine and
the cysteine residue off to the right is an asset ile cysteine so you can clearly
see how an asset ile cysteine is one of the precursors to glutathione and that's
important because we talked about giving an asset ile cysteine as a way of
recharging this SH group in patients with oxidized glutathione but what would
happen if you actually just gave glutathione and I received a number of
comments regarding this well here is a published report of two cases with kovat
19 that were treated with glutathione now you should know in the business that
when you're looking at evidence case reports are the lowest form of evidence
that we have this is not a randomized controlled trial we have no idea whether
or not the two patients improvement was the results of the medications that they
took nonetheless it is a case report and we can see here that there were two
patients living in New York City with history of Lyme and tick borne
co-infections that experience cough and dyspnea and demonstrated radio graphical
findings consistent with kovat 19 these people were given two grams of P o or IV
glutathione now doesn't say which one was given P O or IV and that's important
from my standpoint because when you give polypeptides orally the expectation is
is that they're going to be cut up by the protease --is that are in the
stomach that is the job of the stomach is to cut up large polypeptide chains
into amino acids so they can be absorbed in the intestines
so how bioavailable is P o glutathione some reports show that it may not be
that bioavailable but I guess the question is is if you are cutting up
glutathione you're going to be cutting up into glycine's glutamates and
cysteines which eventually are the building blocks of glutathione the
patients were also given this intravenously
what happened oral and IV glutathione glutathione precursors like an acetal
cysteine like we've just talked about an alpha lipoic acid may represent a
novel treatment approach for blocking NF kappa-b and addressing cytokine storm
syndrome and respiratory distress in patients with Kovan 19 and the reason
why they say that is because in both patients their dissonant improve within
one hour of use now while this is a far stretch from proving anything it does
make it very interesting to think about whether or not patients would improve if
they were given both an acid seal cysteine and IV glutathione after all we
did discuss the potent thrombolytic effect of an acetal cysteine on arterial
thrombosis
hypoxemia and that is pulmonary arterial thrombosis and again the reason why
we're saying this is because von Willebrand factor uses these disulfide
bridges to turn these monomers into multimers essentially polymerizing and
causing the clot with lots of platelets in it of course what I'm waiting for is
the actual clinical trial and we've talked about this one before it is the
study of n-acetylcysteine in patients with kovat 19:00 it's the only one that
I can find for the treatment of severe Cova 19 infections and in fact they say
here that this study is the first to test and acetate in people with severe
Cova 19 infections apparently it looks like it's going to be a non randomized
trial with 86 participants with a parallel assignment and an open label in
this particular trial they're giving an asset eel cysteine at six grams
intravenously per day based on the case reports that we just saw I'm wondering
whether or not el glutathione would be also wise to add to the regimen also
recently published it appears as though a Russian researcher associated with a
medical university also has a similar hypothesis and may have even come up
with this before we thought of it and the proposal is titled endogenous
deficiency of glutathione as the most likely cause of serious manifestations
and death in patients with kovat 19:00 and the abstract goes like this based on
an exhaustive literature analysis and own observations I proposed the
hypothesis that glutathione deficiency is exactly the most plausible
explanation for serious manifestation of death in kovat 19 infected patients the
major risk factors established for severe Koba 19 infection and relative
glutathione deficiency found in covent 19 affected patients with moderate to
severe illness have converged me to two very important conclusions number one
oxidative stress contributes to hyper inflammation of the lung leading to
adverse disease outcomes such as an acute respiratory distress syndrome
multi organ failure and death and number two poor antioxidant defense
due to endogenous glutathione deficiency as a result of decreased biosynthesis
and/or increased depletion of gsh is the most probable cause of increased
oxidative damage of the lung regardless which of the factors aging chronic
disease core morbidities smoking or some other were responsible for this deficit
the hypothesis provides novel insights into the etiology and mechanisms
responsible for serious manifestations of Cova 19 infection and justifies
promising opportunities for effective treatment and prevention of the illness
through glutathione recovering with n-acetylcysteine and reduce glutathione
and in his paper professor paul anakov lists off a number of observations he
saw with some kovat 19 patients here he has patient M 34 year olds with symptoms
of fever mild myalgia appeared on the eighth day after contact with a kovat 19
positive patient and disappeared on the sixth day of disease without treatment
and you can see here that the gsh was about 0.7 1/2 micro moles per liter and
reactive oxygen species which is bad was at two point zero seven five which gives
us an ro s the gsh ratio of two point nine here's another patient forty seven
years of age with symptoms fever of thirty seven point three mile fatigue
here the patient's gsh was zero point nine three three reactive oxygen species
was one point one four three with a ratio of one point to these patients
both got better without treatment okay let's go to patient three first symptoms
such as fever and air hundred appeared on the fourth day after contact with a
kovat of nineteen positive patient and the patient persisted for thirteen days
notice how low this GSHS it's zero point zero seven nine and the reactive oxygen
species or up as high as two point seven three giving a ro s two gsh ratio of
thirty four point six patient are had a fever of 39 degrees centigrade severe
dry cough dyspnea Navigant fatigue and tachycardia
appeared on the seventh day after contact with a kovat and 19 positive
patient she was hospitalized with characteristic radiographic aligns of
kovat 19 and clinical symptoms are persisting to date for 11 days so this
must have been at the time of the writing here the gsh is 0.5 our OS is
3.6 7 7 and again the ratio is as high as 6.9 and so the good professor comes
up with very similar conclusions that we do which is that an acid heel cysteine
as a preventative measure may be very effective the professor says here that
oral administration of n-acetylcysteine as a preventative measure against viral
infections as well as intravenous injection of nak or reduced glutathione
may be effective options against the novel coronavirus however clinical
trials are needed to objectively assess an efficacy of an acetal cysteine and
reduce glutathione for both the treatment and the prevention of this
novel viral infection but don't forget I think there's actually more to it than
just oxidative stress because the clots that they're pulling out of people with
kovat 19 they're finding are very rich in platelets and that means that there
is also the issue of von willebrand factor these von Willebrand factors are
connected to each other by these disulfide bonds and as we've already
talked about an acetal cysteine and reduce glutathione will break these
disulfide bonds and cause them to lyse and potentially relieve the obstruction
in the hypoxemia with kovat 19 again this is all a hypothesis but it looks as
though it's fitting together and I wanted to remind everybody that if
you go to med cram comm and sign up there you will see all of our kovat 19
resources including all of the videos that we have recorded ANCOVA 19 I also
encourage you to check out some of our other offerings like our very popular
EKG interpretation CBC results explained clearly
and vasopressors explain clearly thanks for joining us