Coronavirus Pandemic Update 42: Immunity to COVID-19 and is Reinfection Possible?

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 they recently

update

d it to show a little more in terms of location so you can look. and get closer as you can see the case numbers are starting to rise quite precipitously. I want to highlight this free app called kovat 19 tracker that was developed by a retired obstetrician and gynecologist doctor in Florida and his team of developers at a company. called linked health to look for additional trends and clusters of cases, they have created a platform for users to report if they have symptoms similar to Kovat 19 and if they have been tested, as you can see this application 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 useful tracking tool for hospitals and communities, it's finally time to talk about

immunity

and this It's a complicated topic, so let's continue. go through it quite slowly but at a rapid rate as you will see you have 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 in the virus our spike proteins and They are these spike proteins. peak those that allow it to bind and enter the cell, but inside this virus there is an RNA molecule and it is this RNA molecule that gives instructions to the cell to produce more viral particles, so what you get as a result of that it is more viral.

The particles and of course each of those viral particles have their own RNA that is copied from the original, but remember when that virus particle fuses with the cell, that membrane fuses with this membrane and then the cell shows that it is infected because it has those particles. the surface as well, so the general way we've been testing the pathway is by looking specifically at the RNA and that's the testing that's been done up to this point, the technique that's used is called reverse transcriptase polymerase chain reaction. or rt- pcr takes a small fragment of that RNA and finds a specific sequence that is unique to that sequence and copies it and then takes it and copies it and so it can amplify from the RNA a bunch of DNA that looks like that and Because we have a certain code in that DNA that is unique to that and therefore is unique to this RNA, we can put something nice on it that lights up and that will bind, call the probe and if we see this light up eh, we have a positive test, if on the other hand we do not see that, then the reverse transcriptase will not recognize the specific sequence of that RNA that is specific to this virus and no other, it will not amplify it and we will obtain a negative result. is how we test if someone is positive or negative for kovat 19 or negative for kovat 19, unfortunately from the statistics that I have seen, despite some of the reports from South Korea compared to their tests, I have seen a sensitivity of 60 to 70 percent and some of you may see different numbers, the sensitivity tells you what percentage probability that if someone tests negative, then you can rule it out, although if someone tests negative for

coronavirus

or Cova 19, in this case there are a 30% chance that it can.

I still potentially have the disease and when we talk about isolating someone what we really want to have for sensitivity is something as close as

possible

to 99 or one hundred percent sensitivity, so that has been a problem with respect to these types of tests, so obviously this is the type of test that you want to do in an acute situation, if someone is infected with this corona virus and they have a bunch of these viral particles floating around, it will be easy to detect if they are positive or not and if the person has recovered and there is no more RNA then your test will be negative if your test is negative and here is the key point if the test is negative there are two possibilities: number one, it could be a false negative or number two, they could have cleared the infection and here the problem comes with respect to

reinfection

and that's been the real key question up to this point if you serially test someone and you get something that looks like this positive positive positive negative negative positive positive positive let's say you test them eight times in this situation, what is the reason why this is positive?

Is it because they were false negatives or is it because they were really negative and then reinfected again? You don't really know, especially when you have less than a Hundred Percent sensitivity now, generally speaking, when you actually get

immunity

against the virus, what happens at that point is that antibodies are produced against the virus and specifically they will be these proteins that It is on the surface that will be the easiest to produce antibodies. normally it looks like this, it has a nice constant protein and here are the variables that end up here with these hypervariables where you can actually have different confirmations of proteins that will fit perfectly into this type of spike protein, so when you create these type of antibodies The antibodies will single out these types of cells and mark them for destruction by other parts of the immune system in terms of a timeline starting from scratch.

Here, generally speaking, you'll see positive results at this point when you have the disease until you eventually recover and the virus is no longer detectable and that would be the reverse transcriptase PCR test which is this test here and then at some point , you will develop an antibody response that will then be detected, so hopefully these antibodies will give you immunity to this virus for the rest of your life, which is why you get vaccinated against measles, mumps, rubella, etc. They are now called immunoglobulins, but they are different types of immunoglobulins. There are immunoglobulins that occur early in the immune response and that's called IG M, so M is the first one you would see and then you get an IgG molecule.

If someone were to have an IgG positive for a specific virus, I would say that, generally speaking, you have immunity against an infection. a long time ago, but if your eye GMO was positive, then you would say, ah, this is an antibody against a viral protein that must have occurred recently, maybe in the last few weeks or even days, depending on the immune response, generally speaking , it's more over time. lines weeks to a month or so and what about testing to detect that well the same way we test for these antibodies? Scientists make little bits of those spike proteins, but they're manufactured, and so if they mix their reagents with patients' blood, which may or may not have antibodies, you'll see here that those antibodies will mix together and have something.

What happens when these things mix together and it will turn out to be a positive test and you will be able to tell based on the test in which we will not go into whether it is IgM or IgG, so this type of test here on the right side of this line is just starting to appear, this could potentially be important because although you may not have symptoms of the original infection you will be able to tell whether or not you have been infected using this type of test and we will mention other applications of this later in this video, but please understand that There is a difference between the PCR test and the antibody test.

The antibody test checks whether or not you have immunity to the virus, while reverse transcriptase PCR looks to see if you actually have viral particles still inside your body, so the question in this situation is whether the patient gives a false negative because of these poor sensitivities in these reverse transcriptase PCRs or if the patient is actually becoming infected again, there was a non-peer reviewed article that recently asked some of those questions to answer this article that tries to determine whether or not there is an infection with COBIT 19. Disease with the SARS cub 2 virus conferred immunity to the host for repeated infections.

Now let's review what they did. I want to let you know that this involves research with animals, in this case rhesus monkeys, which are quite close to us in genetic terms. They took four rhesus monkeys and infected all four of them with the SARS puppy virus. They all had similar symptoms. The symptoms and signs you imagine. They lost a little weight. They showed signs and symptoms of the virus. Additionally, they reviewed. viral loads using that reverse transcriptase PCR that we talked about and they peaked at about three days in all of the featured monkeys, they looked at not only the nasal and pharyngeal swabs but they also did anal swabs to make sure that they had verified clearance viral in both places and the peak was about three days after the initial infection, they sacrificed one of the animals and after evaluating the monkey they went to see exactly where the virus ended up in that body, they could see that the virus was in the nose. , the pharynx, which is the mouth, the lungs, which is where most of the virus hangs, the gut, the spinal cord, the heart, skeletal muscle and the bladder.

Then what they did in the remaining three monkeys was they measured the antibodies on day 14, day 21, and day 21. 28 and what they saw in those three remaining monkeys were all the things that you would notice when seeing if someone had immunity, which basically it was that there were increasing signs of antibody production that showed that these monkeys were recovering from the initial SARS puppy infection. For the highlighted virus, they looked at the chest x-rays on day 28 and the chest x-rays were negative. They were essentially normal at that time. The other thing they did was check the viral load at that time and also using reverse transcriptase PCR. and in all of them the viral load was negative, so on day 28 we essentially recovered primates without an abnormal chest x-ray and with an undetectable viral load.

What they did on day 28 was reinfect the remaining three monkeys and monitor them in addition to an initial increase in temperature in all three they did not show any of the signs that they had here with the weight loss and the signs and symptoms that would be expected of an infection viral, none of those signs were present except a very small increase. in body temperature which quickly disappeared and after about five days they euthanized one of these animals and looked to see if there was any kind of anomaly or virus anywhere and they looked at all three of them a total of 96 times to see if there was any virus, any load viral using rt-pcr and the response in each case was none.

When they looked at that euthanized monkey after five days, they showed that there was no viral replication in all tissues, as well as no pathological damage or viral antigen in the lung. tissues, they go on to say, therefore our results suggested that monkeys with SARS-infected pups after recovery were unable to be reinfected with the same strain longitudinally. The monkey that had suffered a single infection in this study did not appear to show signs of recurrence after recovery. Taken together, the team concludes that our results indicated that SARS's primary sleeve for infection could protect from subsequent exposures, which has 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 at this time. was documented several times in his reports on the smallpox epidemic in Trinidad from 1902 to 1904 on page 83 dr.

Schwahn speaks of second attacks, the possibility of second attacks was recognized as early as the 10th century by the Arab Galen de Roz and his experience has been confirmed by many observers to this day, reviewed and documented in several patients he treated. in Trinidad about people who had multiple attacks of smallpox, including some who had been successfully vaccinated and who is the author dr. Marie Francois Raoul SH welt, who happens to be my great-great-uncle, was the chief surgeon at the Colonial Hospital in Port of Spain, Trinidad, despite this, although

reinfection

is rare, so in this case, on the curve From the SARS situation, it seems that the virus is following what we would normally see, that is, if there are not as many changes in the hosts of the virus, the hosts develop immunity and if that is the case, can we get blood tests done quickly to detect antibodies?

It could be very useful if we could check for antibodies because we could see who was really infected, how widespread the infection is, and if it's widespread enough, you could add 50, 60, even 70 percent to get herd immunity, where the virus would not spread as quickly. you wouldn't have to do isolation plus that you wouldn't have to worry about personal protective equipment on healthcare providers who already have antibodies because they couldn't get the disease again here is an article that was published in a science looking for new analysis of blood and basically go over the same things that we've been talking about, companies have been racing to develop antibody tests.

Here's one from the Khan School of Medicine at Mount Sinai. YesterdayThey published a preprint describing a SARS pup. The antibody tests that they've developed are a relatively simple procedure and could easily be scaled up by other labs and then they go on to describe exactly what we've talked about, where they find this spike protein on the outer layers to see if it works or not. it will bind to the antibodies if they are there and if they bind to these receptor binding domains like we talked about, then it would trigger a detection so you can see if the antibodies are there or not.

Here's another biomedical omics antibody test you're still looking for. FDA approval for these Kovat 19 rapid diagnostic tests and you can see here it's pretty simple. We'll put a link in the Below describes this regarding this, but in terms of sensitivity and specificity, let's take a look at what 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 acute phase. In the more chronic phase combined antibody test for the diagnosis of SARS cuff infection, the overall sensitivity of the test was eighty-eight point six six percent, meaning that if you had a negative test, you could be eighty-eight point six six percent. and eight point six six percent confident that it was not a false negative result.

Additionally, the specificity was ninety point six three percent, meaning that if the test was positive there is a ninety point six three percent chance that it was a true positive. High sensitivity means that if it is negative it can be ruled out. High specificity means that if it is positive it can be ruled out. we can rule out and in both cases here we have good results, so we hope that this test will be approved by the FDA soon so that we can do antibody tests to see who has already had the disease and maybe didn't know it.

It will give us an idea about herd immunity and how quickly this virus will continue to spread. Remember that if fifty to sixty percent of the people in a community have already tested positive for the virus, it is very difficult for that virus to spread much further. Health care workers can also get tested and, if they test positive and have already had the disease, that could potentially save equipment for those who have not yet tested positive. Today we review many things. I would offer a couple of reminders. For those healthcare providers who want a refresher course or learning it for the first time, don't forget to go to med cram comm for our free ventilator management refresher and learning course.

I hope to do it during the next few days of this week. Let's review the practical things we can do to improve our immunity as this virus continues to spread through our community. Thanks for joining us.