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