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Coronavirus Pandemic Update 40: Ibuprofen and COVID-19 (are NSAIDs safe?), Trials of HIV medications

welcome to another MedCram COVID-19
update as we look at our Johns Hopkins coronavirus tracker we can see where the
infections are in the world and recently they've updated this to actually show a
little bit more in terms of location so you can actually look and zoom in as you
can see that the number of cases are starting to rise quite precipitously I
want to highlight this free app called the kovat 19 tracker that was developed
by a retired ob/gyn physician in Florida and his team of developers at a company
called health linked to look for additional trends and clusters of cases
they've created a platform for users to report if they have kovat 19 like
symptoms and if they've been tested for it as you can see this app has already
become one of the most popular medical apps and as testing availability and
challenges continue in the United States and other countries apps like this could
be a helpful tracking tool for hospitals and communities it's finally time to
talk about immunity and this is a complicated topic so we're gonna go
through it fairly slowly but at a rapid pace as you'll see you've got a cell in
this case the cell has the ACE 2 enzyme which is the receptor for the virus and
here comes the virus and on the virus our spike proteins and it's these spike
proteins that allow it to bind and come into the cell but inside this virus is
an RNA molecule and it's this RNA molecule that gives instructions to the
cell to make more viral particles so what you get as a result of that are
more viral particles and of course each of those viral particles have their own
RNA which is copied from the original but remember when that virus particle
fuses with the cell that membrane fuses with this membrane and so then the cell
shows that it's infected because it has those particles on the surface as well
so the general way that we've been testing for the via
is by looking at specifically the RNA and that's the testing that's been done
up to this point the technique that is used is called reverse transcriptase
polymerase chain reaction or rt-pcr it takes a little fragment of that RNA and
it finds a specific sequence that's unique to that sequence and it copies it
and then it takes that and it copies it and so it can amplify from RNA a bunch
of DNA which looks just like it and because we have a certain code in that
DNA that's unique to that and therefore is unique to this RNA we can put onto it
a nice thing that lights up that will bind call the probe and if we see that
this thing lights up huh we have a positive test if on the other hand we
don't see that then the reverse transcriptase won't recognize the
specific sequence of that RNA which is specific to this virus and no other it
won't amplify it and we will get a negative result this is how we test
whether or not somebody is positive for kovat 19 or negative for kovat 19
unfortunately based on the statistics that I have seen notwithstanding some of
the reports from South Korea versus their testing I have seen anywhere from
a 60 to 70 percent sensitivity and some of you may see different numbers
sensitivity tells you what percent likely that if somebody is negative then
you can rule it out though if someone tests negative for coronavirus or
negative for Cova 19 then there is a in this case a 30% chance that they could
still potentially have the disease and when you're talking about isolating
somebody what you really want to have for sensitivity is something as close as
possible to 99 or a hundred percent sensitivity so that's been an issue with
regard to this type of testing so obviously this is the kind of testing
that you want to do in the acute situation if someone is infected with
this corona virus and they have a bunch of these viral particles floating around
it's going to be easy to detect whether or not they are positive and if the
person has recovered and there is no more RNA then their test is going to
be negative if their test is negative and here's the key point if the test is
negative there's two possibilities number one it could be a false negative
or number two they could have cleared the infection and here comes the issue
with regards to reinfection and that's been the real key question up to this
point if you do serial testing on somebody and you get something that
looks like this positive positive positive negative negative positive
positive positive let's say you tested them eight times in this situation what
is the reason why this is positive is it because these were false negatives or is
it because they truly were negative and then they got reinfected again you don't
really know especially when you have a sensitivity that is less than a hundred
percent now generally speaking when you do actually get immunity to the virus
what occurs at that point is antibodies are made to the virus and specifically
it's going to be these proteins that are on the surface that are going to be the
easiest to make antibodies antibody typically looks like this it's got a
nice constant protein and here are the variable ends here with these being
hyper variable where you can actually have different protein confirmations
that will fit perfectly into this type of a spike protein so when you make
these kind of antibodies the antibodies will signal out these type of cells and
mark them for destruction by other parts of the immune system in terms of a time
line starting from zero here generally speaking what you would see the positive
results at this point when you have the illness until finally you recover and
the virus is no longer detectable and that would be the reverse transcriptase
PCR test that's this test over here and then at some point you're going to
develop an antibody response which is then going to be picked up so these
antibodies hopefully will give you immunity to this virus for the rest of
your life this is why you get vaccinations for measles mumps rubella
it's etc now these are called immunoglobulins
but they're different types of immunoglobulins there are
immunoglobulins that occur early in the immune response and that's called an IG
M so M is the first one that you would see and then later on you're gonna get
an IgG molecule instead if somebody were to be positive on an IgG for a specific
virus than I would say you generally speaking had immunity from an infection
a long time ago but if your eye GM was positive then I would say ah this is an
antibody to a viral protein that must have happened just recently maybe in the
last few weeks or even days depending on the immune response generally speaking
it's more along the lines of weeks to a month or so and what about testing for
that well the way that we test for these antibodies scientists manufacture little
portions of those spike proteins but they are manufactured and so if they mix
their reagents with the blood from the patients which may or may not have
antibodies you're going to see here that those antibodies are going to mix and
they will have a certain thing that occurs when these things mix together
and it will turn out to be a positive test and they can tell based on the test
which we won't get into whether it's an IgM or an IgG so this type of testing
here on the right side of this line here is just now starting to come on this
could be potentially important because even though you might not have symptoms
of the original infection you will be able to know whether or not you have
been infected using this kind of a test and we'll bring up other applications of
this later on in this video but understand that there is a difference
between PCR testing and antibody testing antibody testing is checking to see
whether or not you have immunity against the virus whereas the reverse
transcriptase PCR is looking to see whether or not you actually have viral
particles still inside your body so the question is in this situation is the
patient testing falsely negative because of these poor sensitivities on these
reverse transcriptase PCRs or is the patient really becoming infected again
there was a non peer-reviewed article that
recently put some of those questions to answer this article set out trying to
determine whether or not an infection with the COBIT 19 disease with the SARS
cub 2 virus conferred immunity to the host for repeated infections afterwards
now let's go over what they did I want to let you know that this does involve
animal research in this case rhesus monkeys which are fairly close to us in
terms of genetics they took four rhesus monkeys and they infected all four of
them with the SARS cub to virus all of them had similar symptoms the symptoms
and signs that you would imagine they lost a little bit of weight they showed
signs and symptoms of the virus furthermore they checked viral loads
using that reverse transcriptase PCR that we talked about and those peaked at
about three days in all of the monkeys of note they checked not only the nasal
pharyngeal swabs but they also did anal swabs to make sure that they had checked
for viral shedding in both places and the peak was around three days after the
initial infection they sacrificed one of the animals and after evaluating the
monkey they went to go look to see exactly where the virus ended up in that
body they were able to see that the virus was in the nose pharynx which is
the mouth lungs which is where most of the virus hung out the guts spinal cord
the heart skeletal muscle and the bladder then what they did in the
remaining three monkeys is they measured antibodies at day 14 at day 21 and at
day 28 and what they saw in those three remaining monkeys were all of the things
that you would notice to see if someone had immunity which was basically there
were increasing signs of antibodies being made showing that these monkeys
were recovering from the initial infection of the SARS cub to virus of
note they looked at the chest x-rays on day 28
and the chest x-rays were negative they were essentially normal at that point
the other thing that they did was check the viral load at that time as well
using reverse transcriptase PCR and in all of them the viral load were all
negative so at day 28 we essentially have recovered primates without a
abnormal chest x-ray and with undetectable viral load what they did on
day 28 was they reinfected the remaining three monkeys and monitored them other
than an initial spike in temperature in all three of them they showed none of
the signs that they had back here with the weight loss and the signs and
symptoms that you would expect with a viral infection
none of those signs were present other than a very small spike in body
temperature which quickly went away and after about five days they sacrificed
one of these animals and looked to see if there was any kind of abnormality or
virus anywhere and they looked in all three of these a total of 96 times to
see if there was any virus any viral load using rt-pcr and the answer in
every single case was none when they looked at that sacrifice monkey after
five days they showed that there was no viral replication in all tissues as well
as no pathological damage and viral antigen in lung tissues they go on to
say therefore our results suggested that the monkeys with SARS cub to infection
after recovery could not be reinfected with the same strain longitudinally the
monkey that had undergone single infection in this study did not appear
to show signs of recurrence after the recovery either taken together the team
concludes our results indicated that the primary SARS cuff to infection could
protect from subsequent exposures which have vital implications for vaccine
design and disease prognosis which is not to say that it would be unusual to
have multiple infections of the same virus this was documented several times
in his reports on the epidemic of smallpox in Trinidad from 1902 to 1904
on page 83 dr. Schwahn talks about second attacks the possibility of second
attacks was recognized as far back as the 10th century by Roz's the Arabian
Galen and his experience has been confirmed by many observers up to the
present day he goes through and actually documents in several patients that he
attended to in Trinidad on people who had multiple bouts of smallpox even some
that had been vaccinated successfully and who is the author dr. Marie Francois
Raoul SH welt who happens to be my great granduncle he was the top surgeon in the
colonial Hospital in Port of Spain Trinidad despite this though reinfection
is a rare thing and so in this case in the SARS curve to situation it seems as
though the virus follows what we normally would see which is if there
isn't that much of a change in the virus hosts develop immunity to it and so if that's the case can we have
blood tests quickly that would check for antibodies it could be very helpful if
we could check for antibodies because we could see who was actually infected how
widespread is the infection and if it is widespread enough you might be able to
actually add 50 60 even 70 percent get into herd immunity where the virus would
not spread as fast and you would not have to do isolation in addition to that
you wouldn't have to worry about personal protective equipment in
healthcare providers who already have antibodies because they wouldn't be able
to get the disease again here's an article that was published in a science
that looks for new blood tests and they basically go over the same things that
we've been talking about companies have been racing to develop antibody tests
here's one out of a Khan School of Medicine at Mount Sinai they posted a
preprint yesterday describing a SARS cub – antibody tests that they've developed
it's a relatively simple procedure and other labs could easily scale it up and
then they go on to describe exactly what we've talked about where they find this
spike protein on the outer coats to see whether or not it will bind to
antibodies if they're there and if they do bind to these receptors binding
domains as we talked about then it would trigger a detection so that you could
see whether or not the antibodies are there
here's another antibody test biomed omics
who's still seeking FDA approval on this kovat 19 rapid diagnostic tests and you
can see here that it's fairly simple we'll put a link into the description
below regarding this but in terms of the sensitivity and specificity let's take a
look at that this was published in the Journal of medical virology the
development and clinical application of a rapid IgM remember we talked about IgM
being in the acute phase and IgG being in the more chronic phase combined
antibody test for SARS cuff to infection diagnosis the overall testing
sensitivity was eighty eight point six six percent meaning
that if you had a negative test you could be eighty eight point six six
percent sure that that was not a false negative result
additionally specificity was ninety point six three percent that means that
if the test was positive there's a ninety point six three percent chance of
it being a true positive again high sensitivity means that if it's negative
you can rule out high specificity means that if it's positive you can rule in
and in both cases here we've got good results so we hope that this test gets
fda-approved soon so that we're able to do antibody testing to see who has had
the disease already and may not have known it that'll give us an idea about
herd immunity and how fast this virus is going to continue to spread remember
that if fifty to sixty percent of the people in a community already have
tested positive for the virus it's very difficult for that virus to spread much
more also health care workers can be tested and if they're positive and have
already had the disease and that could potentially save equipment for those
that have not yet tested positive well we went over a lot of things today I
would offer you a couple of reminders for those health care providers that
want a refresher course or to learn it for the first time don't forget to go to
med cram comm for our free course on updating and learning about ventilator
management I hope to over the next number of days this week go over
practical things that we can do to improve our immunity as this virus
continues to spread throughout our community thanks for joining us