welcome to another MedCram COVID-19 updates now for the first time the u.s.
tops the charts at 85,000 653 infections that are confirmed staggering 24,000
total deaths daily new cases in the United States are continuing to rise and
if we look at total cases in the United States the state of New York
tops that list by a large amount it is the epicenter of the new cases at this
point and because of that supplies are running scarce there's an article here
in the New York Times talking about the scarcity of mechanical ventilators New
York starts sharing ventilators and this was approved by the governor to keep
coronavirus patient's breathing hospitals pioneer a little tested method
you can see there a portable ventilator that ambulances use to transport
patients who are on ventilators they mentioned here that this is not the
first time that this has happened before they did this in Las Vegas when there
was a mass shooting in previous updates here on med cram we showed you dr.
Babcock the ER physician demonstrating that in a video on YouTube also in the
news and updated about six hours ago was a story on Fox by Prisma health that
says that their new innovative ventilator adapter can actually treat up
to four patients on a ventilator at a time there was another ER physician
named Sarah Ferris and her husband who is a software engineer developed this
device called Vesper as it turns out this is a 3d printed device and they are
making it available so that it can be printed in your local hospital in
addition to this the US Food and Drug Administration has granted emergency use
authorization for this type of ventilator and down here you can see a
link other hospitals that want to begin using vesper can receive the free source
code and printing specifications for the device today by registering on christmas
health website and you can see there okay so not so fast because there
is a joint statement that was put out by the American Association for respiratory
care in conjunction with a number of other societies which are pretty
heavy-hitting like the Society for critical care medicine issued a joint
statement basically saying no we don't think that this is a good idea the
reasons they include here are quite numerous including the fact that volumes
could go to the most compliant lung segments that it would be impossible to
manage the positive end expiratory pressure among other things and you can
read some of the others and they give references as well in this joint
statement so it's going to be interesting to see what happens because
as the New York Times pointed out the other option is death the AARC however
is saying that it could jeopardize both patients on the ventilator I think
regardless of which way you take it it'll be clear that there'll be people
taking care of people on ventilators that aren't used to taking care of
people on ventilators if you or if you know somebody that's good to be taking
care of somebody on the ventilator we wanted to offer this course as a
refresher on mechanical ventilation okay I wanted to continue our discussion with
improving immunity we talked before about the beneficial effects of an
elevated body temperature with respect to killing infections in the virus and
we are going to move on to other things but I wanted to restate and re underline
the importance of rest and sleep in terms of the activation of the immune
system especially at a time like now where people are very concerned they may
not be getting enough sleep it's important for us to not underestimate
the benefits of sleep now we're just going to review a little bit but if you
want to know more in detail go back to update 17 on the corona virus that we've
done but real briefly this was a study that looked at the effect of sleep
deprivation on response to immunization the participants were sleep deprived and
given a vaccine to the influenza virus and those that were
sleep-deprived had a much better immune response in terms of antibodies to the
vaccine and the conclusions that the author's drew were these results
indicate that the response to the influenza vaccination is likely to be
impaired in individuals who suffer from chronic partial sleep restriction
because adults who show poor responses to vaccines and other antigenic
challenges also experience higher rates of clinical illness our findings support
the concept that adequate amounts of sleep are needed to maintain resistance
to an infectious challenge such as kovat 19:00 this is the other study that we
looked at in update 17 and it looked at the sleep habits how long they slept and
what was the efficiency of their sleep in terms of 14-day baseline and then
they went ahead and dropped rhinovirus filled drops into the nasopharynx of
these subjects and they waited to see how many of them would develop the
common cold symptoms and what they found was quite astounding they found that
those with an average sleep duration of less than 7 hours were not 10% more or
50% more or even a hundred percent more likely to develop the cold but actually
almost three times more likely to develop a cold and when they looked for
confounders these things could not be explained in terms of differences in
pre-challenge virus specific antibody demographics season of the year
body mass socioeconomic status psychological variables or health
practices and so here we have at least four rhinovirus evidence that poor sleep
efficiency and shorter sleep duration in the weeks preceding and exposure were
associated with a lower resistant to the viral illness but there's even more
research that just came out last year and this is the focus of sleep that I
want to look at today so the first thing that you have to understand is that
there is a cell which is infected with a virus and in this case
it was a CMV infected cell CMV stands for cytomegalovirus it's a common virus
that can cause a chronic infection here we have the nucleus and because this
cell is infected with cytomegalovirus it makes its normal proteins on the cell
surface so that the cells of the immune system would recognize it but it also
puts a little portion of that cytomegalovirus protein out on the
surface to let the immune cells know that it's a infected cell and so these
regular proteins that are made in the cell are known as an mhc1 that's not
that important to understand but that's the name of the protein this here is a
portion of the virus that lets the immune system know that it is in fact an
infected cell there are other proteins that are also on the cell and these
proteins help immune cells dock with them
so that they can make the appropriate determination of whether or not this
cell should be destroyed or should survive and this protein is known as I
cam I see a M so far so good now let's bring in our immune cell it's
our cytotoxic T cell it's responsible for going around and making sure that
cells are not infected and taking care of cells that are infected and this
would be the cells that would be going around and getting rid of corona virus
infected cells so they don't produce more virus to infect more cells and in
fact if this can be done early in the course you would have a limited disease
and it wouldn't lead to many many cells being infected causing many T cells to
have to try to fight and causing that cytokine storm well there's a couple of
proteins on these T cells so this is a T cell and it's a cytotoxic T cell not
toxic to you pet cytotoxic to the cell that's infected these are actually your
friends so there is a receptor on the T cell that sees that little particle of
the virus and understands that CEL needs to be destroyed and that is
called the t-cell receptor or the TCR the TCR also activates right next to it
and I'll show this here in green that it's activating the beta integral this
interaction between beta integrins and the I cams allow for a very strong
docking that allows these cells to bind very very strongly to these infected
cells and that allows these T cells to secrete cytokines that will shut down
and kill the cell before it produces more viruses so it's very important that
the beta integrins and the eye cams are able to bind together normally the beta
integrins are not activated and they will not bind these eye cams otherwise
your immune system would start to destroy your own body so they're shut
down but there are certain situations where they need to be turned on and if
they are not turned on your immune system is not going to work very well
well in this case it is the TCR which activates these beta integrins and
allows this to occur the purpose of this article was to see whether or not things
can affect this turning on of the beta integrins and sure enough they
discovered that there is a receptor called the G alpha s receptor and this
receptor is coupled to what is known as a g-protein and it's coupled to an
enzyme known as a dental 8 cyclase there's a lot of moving parts to this
receptor but I'm going to simplify it and show you that essentially it takes
ATP which is abundant in the cell and it converts it into something called cyclic
a MP and as it turns out cyclic a MP shuts down the ability of the TCR to
activate the beta integrase so the question is is what is actually
stimulating this G alpha s receptor there's a number of things that can
activate this one of them is epinephrine typically dopamine histamine
serotonin and the thing about all of these things that can actually stimulate
this receptor here they're all quite elevated when you are awake and so you
can see it's possible that epinephrine dopamine histamine serotonin could
stimulate this receptor which would eventually convert ATP into cyclic AMP
II which would then inhibit TC Aras ability to have the beta integrand
buying with I cam and to have this t-cell destroy with cytokines this
infected cell so is it possible that sleep could stop epinephrine
dopamine histamine and serotonin from binding this receptor and allow the beta
integral and the I cam to bind tightly so that the immune response would be
more robust and so now the title becomes a little bit more understandable GA s
coupled receptor signaling and sleep regulate integrin activation of human
antigen specific t-cells and this was published last year in the Journal of
experimental medicine they infected these with the epstein-barr virus as
well and so we've got data for both of those so here we can see the data for
CMV specific cd8 cytotoxic T cells they looked at isoproterenol which does hit
that receptor epinephrine which does hit the receptor and norepinephrine as well
and here on the x-axis as we increase the concentration you can see that that
effect is that the binding of I cam 1 as a percentage of the control starts to
drop off precipitously and you can see that here with prostaglandins as well as
adenosine in the e VV or the epstein-barr virus cell cultures that
were infected as the increased concentration of the same substances
that we talked about you can see that the eye cams do drop so it's one thing
to say that these specific substances make it drop but the question is is
whether or not sleep is actually beneficial in making sure that the cells
can bind to their targets and take them out and that's what they attempted to
show here in human patients what we see here again
is the same thing on the y-axis we're looking at I cam binding but we have two
types of patients in this scenario we have the ones that are filled in with
black circles and these were the ones that were sleeping at night and awake
during the day as opposed to these open circles which are white in the middle
where they're awake during the night and also awake during the day and so you can
see the effects here in the CMV infected cells on the left and the EBV infected
cells on the right in the nighttime which is shaded here and over here as
well at least at two o'clock in the morning and here at six o'clock in the
morning there was a statistically significant increase in I cam binding in
these patients that were sleeping at two o'clock in the morning as opposed to
being awake at two o'clock in the morning and I just wanted to point out
for those of you who are doing shift work that so long as you are working at
night and going home and sleeping with your lights off and no light coming in
through the windows and you do this every single day throughout the weekend
you can also get the same benefit from getting sleep even though it's when the
Sun is up and then they decided to look at that over the different types of
differentiation of these cytotoxic T cells they looked at ones that were
early in their life intermediate in the cell life and late in the cell life and
what they found was this effect seemed to be the strongest in the early phase
of the cells life despite the fact that it didn't have a lot of these G
receptors that we talked about that might suggest that it's the early cells
that are being amplified against the infection at hand
that is more influenced by the effect of sleep versus awake so the conclusions of
the authors are this we show here that several G alpha s coupled receptor
cd8 T cells these are the ones that are doing the killing here whereas sleep up
regulates integrand activation by suppressing G alpha s coupled receptor
signaling given the importance of integrand
activation for the formation of immunological synapses our data suggests
a critical role of conditions like sleep that are characterized by low-level G
alpha s coupled receptor ligands in boosting the t-cell responses and I'll
tell you it's those t-cell responses that are very important in your immune
system getting rid of corona virus infected cells so you can imagine the
current scenario and it doesn't take a lot of drawing on here to modify this
picture for the current kovat 19 situation sleep is important and you
don't have to go to the store to buy it and you don't have to wait for a
pharmacist to dispense it it's something that we can do
put down your iPads put down your phones and go to sleep and wake up with a
better immune system for those of you who have difficulty sleeping if you have
insomnia we have a free course at Meg cram comm on how to deal with insomnia
so please check that out thanks for joining us