Update 96: RNA Vaccine; Ivermectin; von Willebrand Factor & COVID-19

Medcram.com what another medcram covid-19 update we have looked at Canada in a long time. It seems as though they’ve avoided a lot of these recent spikes and their daily deaths continue to be at new lows since the pandemic broke.

The big news of the day of course is modern has RNA vaccine, which we’ll talk about a little bit before we get to that though. I wanted to talk a little bit about thrombosis as we were talking about before and some new research that’s come out in terms of ivermectin as well. First of all, let’s talk about thrombosis real quick.

And as most of you know who are regulars on medcram, you’ll know what we’ve talked about in terms of the hypothesis, which was that SARS Covey two hits the endothelial cells which causes a reduction in ace2 and that causes an increase in Angiotensin II a reduction in Angiotensin 1 7 which leads to reactive oxygen species in the form of superoxide. In this case that’s causes endothelial cell dysfunction which causes an increase in Von Willebrand factor.

A leading to thrombosis. Well, it seems as though this idea and hypothesis is now being picked up fortunately at a number of centers around the world. Here’s one for instance from Russia at the State University at St. Petersburg State University a senior research associate named Anna acts and Nova is reported to be advancing a hypothesis that severe course of covid-19 may be associated with the Von Willebrand factor one of the main components of the blood coagulates.

Elation system and this article goes on to report that the replication of the virus stimulates the development of micro damage on the vessel walls. And in response to this the body releases Von Willebrand factor into the blood trying to patch possible holes and as a result the risk of thrombosis increases and as we talked about it says here today 800 way in which the level of Von Willebrand is regulated in the blood has not yet been fully studied. However, it is known to be stored in.

Ocular endothelial cells in special organelles where it secretes in the form of multi MERS as soon as some damage to the vessel occurs that in order to eliminate it a Cascade of blood coagulant as launched in the body in which Von Willebrand factor takes an active part. They also go on to talk about how this is affected by different blood groups, which were seeing the ABO system affecting also mortality in Von Willebrand. So there may be a connection there as we’ve brought up before.

She goes on to say I hypothesized that the level and activity of Von Willebrand factor might be important predictors of covid-19 morbidity and mortality and my also itself be involved in the disease process in order to confirm this hypothesis. It is necessary to carry out a large-scale and comprehensive Research into the level and activity of Von Willebrand factor in people affected with SARS Covey to who have mild or severe course of infection. Well, I’m so glad that people are looking

at this because I also believe that this is one potential reason why this is happening. Here’s another group from thrombosis research that will be published next month 2020 and this article is titled targeting raised Von Willebrand factor levels and macrophage activation and severe covid-19 consider low volume plasma exchange and low dose steroids. And basically what they’re talking about in this article is that because of Von Willebrand factor is such a very long

Large protein that you really can’t get it out of the system. They say here that large size High molecular weight Von Willebrand factor multimers, which are on the order of 5000 to 10000 kill adult and since eyes are so big that the only way to really get them out is through something called plasma exchange and what they found before was that plasma Von Willebrand factor levels reduce after plasma exchange. So they say that potentially in these severe patients plasma exchange may actually be beneficial in

getting these multi MERS down and preventing thrombosis. And here’s another article that was published in June of twenty 20 titled micro thrombotic complications of covid-19 are likely due to embolism of circulating endothelial derived ultra-large Von Willebrand factor decorated platelet strings kind of like beads on a string and you can read the letter below.

But here’s the key Point endothelial derived ulv wwf’s multimers anchored to the endothelial surface of the vascular wall recruit platelets and initiate micro. Thrombo Genesis within the micro vasculature leading to large micro thrombi strings composed of platelets. And again these Von Willebrand factor complexes like beads on a string structures where platelets firmly adhere to these Von Willebrand factor.

Factors instead of roll on the strings platelets once adhered to these strings are rapidly activated causing platelet aggregation and also recruit leukocytes. Remember what we talked about in our last update that they saw quite a number of megakaryocytes associated with this these Aggregates grow until they become sufficiently large and can no longer be held onto the strings against the force of blood flow and released from endothelial cells into circulation. It appears to us that in

Covid-19 micro thrombotic disease large amounts of circulating complexes of endothelial derived ulv wwf’s decorated platelet micro thrombi strings are filtered in the microvasculature as an embolism. That means that they move until they can’t move anymore or develops in the microvascular in situ. That means right where they are causing micro thrombotic occlusion. And this is what causes our hypoxemia without stiff lungs.

If you want to go back and see the medcram video where we talked about this that was published back in early may go to update 67. Of course, we’ll put a link in the description below. So I’m really glad that they’re looking at this because I think this could be a definite possibility. However, I want to introduce another possible reason why there could be blood clots and that is connected to Ivermectin and then of course we’re going to talk about modern has RNA vaccine here in just

Second. So here’s a paper that has been released but not peer-reviewed titled ivermectin for covid-19 treatment clinical response at quasi threshold doses via hypothesized alleviation of CD 147 mediated vascular occlusion. So this is interesting because CB 147 is a protein that is on the red blood cell red blood cells of course are found in blood clots as well as thrombin and fibrin.

Vibrant Etc. But you may recognize CD 147 as being the entry point for malaria into the red blood cell. Well as it turns out as we talked about before the CD 147 protein is also considered by some a binding site for the spike protein on SARS Covey to now, of course, this doesn’t really help the virus if it goes into red blood cell because while there’s no nucleus in a red blood cell and if there’s no nucleus

Then there doesn’t need to be any ribosomes at least immature red blood cells because there’s no protein synthesis occurring there’s no protein synthesis occurring the virus can’t replicate and so red blood cells are kind of a dead end Target because they’re not gonna be able to reproduce themselves in a red blood cell. They can only do that in a cell that has the Machinery to reproduce it would be like somebody hijacking a plane with no fuel or engines in it’s not going to go anywhere. However, the problem may be that these virus at least the theory goes

goes that the virus binds the CD 147 and tends to make these cells sticky and accumulate and cause thrombosis and that’s what this article is talking about. And for that I want to jump down here to the third paragraph. They say here the proposed catch and clumps scenario for covid-19 has a parallel and malarious. We just talked about CD 147 is Central to the Infectious process of malaria into the red blood cell. But what is it that’s happening in covid-19.

For that lets go to the second paragraph. They say here the potential for major dose response gains is evaluated based on studies indicating that Ivermectin Shields SARS Covey to spike protein and at this Spike protein is supposed to be able to buy ins of CD 147 but Ivermectin prevents this from happening it also potentially prevents it from binding to the ace2 receptor now because of the Abundant distribution of this CD 147 on red blood cell.

Owls it’s not going to be able to bind to the red blood cell and it prevents therefore this hypothesize catch and Clump framework. So catch and Clump meeting the virus catches the red blood cells by 147 and then causes this clumping to occur which may be the basis for this thrombosis. They say here this framework, whereby virally mediated bindings of red blood cells to other red blood cells platelets white blood cells and capillary walls impede the

Flow which in turn May underlie keyboard abilities of covid-19. The reason why this is important they believe is because Ivermectin may actually prevent not only this catching and clumping but it may also prevent infection of the virus into cells where they can cause replication and why do they believe that well this again is not a peer-reviewed study. And in fact, it’s not even a prospective study, but in a retrospective study and of course retrospective Studies have all sorts of problems.

alms with them and biases but nevertheless a retrospective study looking at Ivermectin showed that in a study of a hundred and seventy-three covid-19 patients treated with IV M or Ivermectin in for Florida hospitals at a dose of 200 micrograms per kilogram yielded a 40 percent reduction in mortality compared to 107 controls and that stabilization then improvement over 122 days frequently occurred for patients who had a

Deteriorating oxygen status now previously in our updates. We talked about the modality of ivermectin and how it potentially inhibited the nuclear transport system of converting and transporting viral proteins into the nucleus of the cell. This is a brand new and novel theory that is suggesting that Ivermectin actually interferes with The Binding of the tsar’s Covey to virus with the receptor. Not only

On the cells that might cause viral replication but also on the red blood cells, which don’t the importance here being of course with red blood cells is that they may be the basis for this clotting in patients. Now the thing that we have to remember, of course again that this was a retrospective study and not a prospective study here is a great article in nature that looked at Ivermectin a systematic review from antiviral effects to covid-19 complimentary.

So what is the use of ivermectin and covid-19 this tries to look at the relevant data not only in covid-19, but other viruses as well and it’s a great reference. And of course, we’ll make a reference to it in the description below. But what does it have to say about covid-19? They say here Ivermectin owing to its antiviral activity may play a pivotal role in several essential biological processes. Therefore could serve as a potential candidate in the treatment of different types of viruses including covid-19.

Teen however clinical trials are necessary to appraise the effects of ivermectin on covid-19 in the clinical setting and this warrants additional investigation for probable benefits in humans in the current and future pandemics notice. They say here that on April 10th 2020 the FDA issued a statement concerning self-administration of ivermectin against covid-19 referring to recently published in vitro study on the subject. So notice what they say here because the in vitro study on the subject.

I looked at the dosages and those are noted down here because the type of range in the in vitro study is in the microgram range microgram here the blood levels of ivermectin at safe. Therapeutic dosages in patients is really in the nanogram per milliliter range. And so this brings up the question about can we really take the in vitro studies and make them beneficial in the in Vivo state in other words?

What’s going on in the test tube in vitro? Is that really what’s going on in Vivo? And it looks as though you have to get pretty high concentrations at least in these in vitro studies that may not be possible at least in a safe range in human beings. It doesn’t mean it can’t happen. But it means that we need to test these results in actual patients prospectively to see whether or not it’s going to work. Okay, let’s talk about the big news of the day and for that we turn to stat news.

First Data for moderna covid-19 vaccine show it Spurs and immune response. I just want to make sure everyone is reminded that I have no stock in moderna and no Financial connection to this company. So, let’s see what’s going on.

Basically, all you need to know is right here in the first three lines Wilderness covid-19 vaccine LED patients to produce antibodies that can neutralize the novel coronavirus though. It caused minor side effects in many patients according to the first published data from an early stage trial of the experimental shot. Well, where was it published? It was published in the New England Journal of Medicine. So let’s take a look at that article.

And here is that article titled and mRNA vaccine against ours Covey to preliminary report.

Now remember this is important to understand that this mRNA vaccine is really unlike any other one that has been done before here. You’re not introducing a protein into the patient so that they can make antibodies against it and have memory made against it. No here. We’re introducing a messenger RNA which will go into your native cells and that messenger RNA much like the coronavirus will cause the Machinery of your cell to

produce the protein that is a foreign protein that will cause the immuno genic response and that will cause the antibodies so because this was an early trial early in terms of phase 1 Phase 2 here what they’re trying to do is figure out how much of this vaccine needs to be given to have an adequate immune response without having too many side effects that’s too small you won’t have a very good immunogenic response if it’s too large you could have

have some side effects and so it’s trying to find the Goldilocks if you will right dose so that they can now after determining that do a phase 3 trial where they are planning on starting that very shortly actually and see how that works in a much larger population but at the appropriate dose so as you can see here what they did was they looked at a number of different dosages they looked at the 25 microgram dose the 100 or the 250 microgram dose and in fact

There were 15 participants in each group and basically the bottom line of this study and there’s a lot of data in this study to go over and we might be looking at this over the next couple of updates, but it’s kind of exciting the conclusion was is that the MRNA 1273 vaccine which is the vaccine that they’re looking at induced in anti SARS Covey to immune response in all participants and no trial limiting safety concerns were identified these findings support further development of this vaccine.

Now if we look at the results here, we can see the 25 microgram group The 100 microgram group and the 250 micrograms group and you can see here that over the number of days on each of those that the reciprocal endpoint titers did go up and you can take a look at the rest of these here. I don’t want to get into a lot of the details because it’s very complicated suffice to say that at the end of the day what they noticed was that there was two injections that were necessary to get the

Once that they wanted here’s a nice graph though about what I’m interested in is well, which is what were the side effects in each of these dosages and after vaccination one and after vaccination to and here you can see things broken up pretty well. We’re gray is a mild symptom blue is a moderate symptom and this yellow is a severe symptom so you can see here any systemic symptom for the most part you could see that there was a dose-dependent.

Relationship and it got worse after vaccination to in terms of arthralgias fatigue fever chills headache. Myalgia nausea any local symptom size of erythema or redness or size of in duration or swelling or pain at the site generally speaking was fairly mild to moderate in vaccination one and usually worse in the higher 250 microgram dose.

Whereas in vaccinations to generally speaking, there were more side effects. And again worse in the 250 microgram dose group and based on these results and also in terms of where the company wants to go the dose that they are going to look at going forward is the 100 microgram dose.

As you can read here, it says a large phase 3 efficacy trial expected to evaluate. The 100 microgram dose is anticipated to begin during the summer of 2020 and I believe that is going to be starting this month. It’ll be interesting to see how long the antibody response lasts and if things keep up the way they are we may have a vaccine here in the early part of 2021. I think the question of safety is still there.

Sometimes the true level of safety doesn’t come out until you get into phase 3 trials and indeed even in post-marketing and of course phase 3 is going to tell us whether or not this thing actually prevents people from getting coronavirus. Don’t forget it that if you want to follow other vaccines that are being developed for covid-19 to follow at wraps dot org, which will leave a link in the description below there. They have not only the

The vaccine from moderna but also the other ones for instance from the University of Oxford and also Pfizer Etc coming up. We’re going to talk in future updates about the long haulers. These are people that seemingly have not recovered from their coronavirus infection not just in a couple of days or weeks but in some cases even up to months and why is that happening? Also we’re approaching our 100th update.

Might be a good time to do a little retrospective review. Thanks for joining us.


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