Trialsite interview of medcram (Dr Seheult)

[-] TrumpLyftAlles | 2 points | Aug 12 2020 23:08:18

My rough notes. Quotes are only approximate; don't quote me.

This is the best part, for me. It's near-verbatim, just some verbal filler removed, so I feel honest quoting it.

So do we use it, and find out later it didn't work, or NOT use it and find out that it does work, and we didn't use it. I think I'd rather make the first error than the second error.

I have this thought all the time. Given the facts that (1) ivermectin is ridiculously safe and (2) dirt cheap, WHY does it make sense for the null hypothesis to be that it DOESN'T work? Give it to patients, maybe it helps, maybe it doesn't, it for sure doesn't do any harm. So make the null hypothesis that will or will not be borne out by the trials, that ivermectin DOES work, because there's a large potential up-side and no down-side.

Just the fact that they are actually using ivermectin in the hospital is encouraging. Aside from Eastern Virginia Medical School and a one-shot from a NY doctor, and Broward County of course -- there's not much record of ivermectin use in the US.

Notes:

The host says there's a clinical trial underway at Johns Hopkins. Unfortunately that trial dropped ivermectin.

Wow! Dr. Seheult is using IVM in the hospital. "Give it one time, usually that's good for about a week."

The theory is that the virus gets into the nucleus and shuts down the nucleus shutting down the immune response.

We see this long incubation period, sometimes people are aymptomatic. Why is that? There's a feeling that the virus reduces the immune response.

I didn't follow this reasoning. Hmmm. The virus is multiplying, no symptoms. I guess the symptoms appear when the immune system is broken so the symptoms occur? ??? I don't get it.

Ivermectin shuts down the transportation system (so the immune system isn't affected), so the virus can be cleared.

IVM has been used for decades. It's a relatively safe medication.

So do we use it, and find out later it didn't work, or NOT use it and find out that it does work, and we didn't use it. I think I'd rather make the first error than the second error.

In the hospital, they're are using covid convalescent plasma. Hopefully the original patient's antibodies help the second patient.

We're using Remdesivir.

... interest flagged...

[-] stereomatch | 2 points | Aug 13 2020 17:12:24

We see this long incubation period, sometimes people are aymptomatic. Why is that? There's a feeling that the virus reduces the immune response. I didn't follow this reasoning. Hmmm. The virus is multiplying, no symptoms. I guess the symptoms appear when the immune system is broken so the symptoms occur? ??? I don't get it.

The reasoning is that the symptoms actually are reflective of the degree of immune response.

So if the immune response is contained and steady, it shows less symptoms.

Which is a bit odd sounding - since we are used to assuming that the asymptomatic cases are the ones with robust immune response (which may be the case if they have been exposed to TB/BCG vaccination, or another virus variant - maybe they mount a relatively mild but early defense - all the while having overall activity still low).

https://www.reddit.com/r/ivermectin/comments/i81t9s/_/ Trialsite interview of medcram (Dr Seheult) - section on ivermectin

Dr Seheult (medcram) does say in this interview that the unique thing about covid19 is the long gestation period before symptoms appear (but isnt that the case with colds too ?) - and that supposedly ties into the now often-mentioned ability of this virus to fool the immune response from not being triggered early enough - something about how the virus gets into the nucleus within the cell - where it leads to reduction/staving off of early immune response.

what the theory is what the virus and the proteins associated with it gets into cell - and into nucleus of cell - which leads to inhibition of the immune response you may notice covid19 has a long incubation period - sometimes people are asymptomatic - why is that ? well there is a feeling that the covid19 proteins reduce the immune response from the body well what happens here is those viral proteins hijack a transportation system in the cell - and this transportation system allows these proteins to get into the nucleus (ie into cell and then further into nucleus of the cell) what ivermectin does they feel is to shut down that transportation system and prevent the virus from shutting down the immune system based on the microbiological reasoning that has come out - and there is a plausible mechanism for it the question is will it work on a randomized controlled basis - but the studies are still pending

Dr Yo interview of Adam Gaertner:

https://www.reddit.com/r/ivermectin/comments/i81wzl/_/ Dr Yo interviews Adam Gaertner - ivermectin, vitamin c

Adam Gaertner also points to this "new" explanation - how virus gets into cell nucleus which prevents creation of early interferon.

And how supposedly ivermectin prevents/hinders this.

NOTE: my transcript of this Dr Yo/Adam Gaertner interview is very sparse - they discuss this ivermectin/covid19-suppression of interferon production/nucleus a few times - once at the beginning:

ivermectin/interferon connection

and then later when Dr Yo says the interferon angle he was not as familiar with, but is intriguing.

Dr Yo also mentions the carbohydrate/glucose angle - and they discuss it - where Dr Yo is very happy to get confirmation of his theory that covid19 virus was hiding by glucose/sugars getting attached to virus - which reduces the visibility of the structures on the virus (the "antigens" that immune system is to learn to recognize).

Adam Gaertner also mentions the known contraindications for ivermectin:

alcohol
meningitis
avoid giving to infants, and thus breast-feeding mothers and pregnant women - according to FDA guidelines on ivermectin - although the evidence Adam Gaertner says is not compelling, since it has been given to young in South America and pregnant women in Africa with few significant adverse reports.

FDA approved - except for very young, pregnant - but world experience suggests few complications even in those segments: - south america - young - africa pregnant

Adam Gaertner says ivermectin effect reduced by dexamethasone steroid but not by other steroids:

contraindications: - alcohol - dexamethasone inhibits kinetics of ivermectin other steroids ok methylprednisone is ok

[-] TrumpLyftAlles | 3 points | Aug 13 2020 17:40:26

The reasoning is that the symptoms actually are reflective of the degree of immune response. So if the immune response is contained and steady, it shows less symptoms.

Huh, that is counter-intuitive. I guess you're saying that by the time people become symptomatic, the virus has spread widely and has already disabled the immune system?

Ugh.

Adam Gaertner also mentions the known contraindications for ivermectin:

avoid giving to infants...

I tweeted this out the other day, and Adam follows me (he is @veryvirology) so I suppose he won't be saying that anymore.

Ivermectin is safe for everyone including young children.

Of 170 infants and children weighing < 15 kg who were treated for scabies with oral ivermectin, there were only seven reported mild adverse events and no serious ones.

https://pubmed.ncbi.nlm.nih.gov/31344258/

You said:

Really? I haven't heard of this. What would I google, to learn more? "covid-19 sugar" doesn't sound promising.

There is this recent article that says the virus produces an enzyme called nsp16 which it uses to change it's RNA cap, which prevents the cell's immune system from perceiving the virus as a foreign body that should be attacked. (Wow, that was a crappy sentence.)

Thanks for doing the work of listening to those videos. It's really difficult for me: hard of hearing, no attention span.

The long initial period (6-7 days?) during which people feel fine but they're shedding virus -- that's the really evil feature of this pandemic. "Stay home if you're feeling sick." Too late!

In an ideal world, we would all have a box of cheap one-minute tests in our medicine cabinets, and every morning we would start the test then brush our teeth while we wait for the result.

Something like that is going to be necessary even after the someday-vaccine is widely distributed -- given the recent dismal news (it was news to me, anyway) that it may only 80% effective (the FDA is demanding only 50%) and the coronavirus may mutate and come in new flavors regularly, like influenza.

I really really hope ivermectin proves to provide good prophylaxis. The we'll brush our teeth with tooth paste "with Fluoride and Ivermectin!"

Or some other drug. I'm not married to ivermectin. We talked about it, but the spark wasn't there.

[-] converter-bot | 1 points | Aug 13 2020 17:40:41

15.0 kg is 33.04 lbs

[-] stereomatch | 1 points | Aug 14 2020 00:05:38

The reasoning is that the symptoms actually are reflective of the degree of immune response. So if the immune response is contained and steady, it shows less symptoms. Huh, that is counter-intuitive. I guess you're saying that by the time people become symptomatic, the virus has spread widely and has already disabled the immune system?

Yes, I recall now the difference between colds having gestation period and covid19 having gestation period - I think Dr Seheult (?) ie medcram may have discussed it some time ago - commenting that what is odd about covid19 is that it is infective while patient is asymptomatic which is not what happens with colds (ie other coronavirus common colds).

Now I dont know if that is true - but I seem to recall some some distinction that was made that made covid19 exceptional vs common colds (which also have gestation period before symptoms but apparently are not infective or as infective ?).

avoid giving to infants... I tweeted this out the other day, and Adam follows me (he is @veryvirology) so I suppose he won't be saying that anymore.

Adam Gaertner didnt say dont give to babies - but he recited the FDA guidelines, and then pointed out why those guidelines may not be supported by actual ground data.

It could be that your comment on twitter had him follow that thread or that caveat - I dont know.

Dr Yo is very happy to get confirmation of his theory that covid19 virus was hiding by glucose/sugars getting attached to virus - which reduces the visibility of the structures on the virus (the "antigens" that immune system is to learn to recognize). Really? I haven't heard of this. What would I google, to learn more? "covid-19 sugar" doesn't sound promising. There is this recent article that says the virus produces an enzyme called nsp16 which it uses to change it's RNA cap, which prevents the cell's immune system from perceiving the virus as a foreign body that should be attacked. (Wow, that was a crappy sentence.)

I searched google.com for: covid-19 carbohydrate virus antigens shield

https://www.forbes.com/sites/jvchamary/2020/05/04/coronavirus-vaccine-sugar-shield/amp/ Unlike HIV, Coronavirus Has A Weak Shield. Why Does That Matter?

Sugars or ‘glycans’ play many roles in nature, such as helping proteins fold into stable structures. “The sugars are really central in orchestrating that folding mechanism,” says Professor Max Crispin, a glycobiologist at the University of Southampton. And in the case of viruses like SARS-CoV-2, those sugars also form camouflage. “This spike is like the wolf in sheep’s clothing because the carbohydrates that cover it are human-derived.” Crispin’s team recently mapped the sugars attached to SARS-CoV-2′s spike, as reported in a new study published in the journal Science. This research identified the location of 22 ‘glycosylation sites’ where glycans are attached to the spike (66 in total as the protein consists of three identical parts) and the types of sugar at each site. This work involved using mass spectrometry, chopping-up the protein and weighing the fragments in a vacuum to determine the chemical composition of each piece. The details of the glycans were then mapped onto the structure of the spike protein. How does SARS-CoV-2 compare to HIV, which is infamous for its ability to evade — and infiltrate — the immune system? While the two have a similar number of glycosylation sites and the SARS-CoV-2 spike is larger than that of HIV, the coronavirus’ glycan shield is actually less dense and the sugars have a different chemical composition. A glycoprotein covered in a relatively large percentage of mannose-type sugars is a tell-tale pattern of microbes. On HIV about 60% of a spike’s glycan shield is made up of mannose and so, though the shield is dense, it doesn’t resemble a protein made by normal cells. By contrast, Crispin’s map of sugars has revealed that around 30% of the glycans attached to SARS-CoV-2′s spike are mannose-type.

Dr Yo/Adam Gaertner interview video mentioned something about ABO blood type:

dr yo - abo blood type antigens are sugar .. he been saying older people haemoglobin - RBCs dr yo - carbohydrate binding virus

Blood type may not just be type O less susceptible, but there may be a matrix of susceptibility between infector and infectee blood types.

This opinion article about ABO blood type relates to the general news about type O being less affected vs other types, but it relates it to the sugar types - and goes further to suggest there may be a transmission matrix ie transmission between blood types may have different infectivity/severity:

https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008556 Harnessing the natural anti-glycan immune response to limit the transmission of enveloped viruses such as SARS-CoV-2 doi:10.1371/journal.ppat.1008556 May 21, 2020

Another example concerns the enzymes that are involved in the synthesis of the ABO histo-blood group antigens. The A and B enzymes catalyze the transfer of an N-acetylgalactosamine and a galactose, respectively, in α1,3 linkage on a precursor structure called the H antigen, generating the corresponding A or B antigens. They are encoded by distinct alleles at the ABO locus. The O alleles are null alleles responsible for a lack of transferase, in which case the H antigen remains unchanged. O alleles in the homozygote state confer blood group O, which is characterized by a complete absence of A or B antigens [5]. Under stimulation by bacteria of the microbiota that present glycan motifs similar to either A or B antigens, blood group O people develop so-called “natural” anti-A and anti-B antibodies, whilst blood group A and B individuals develop either anti-B or anti-A antibodies, respectively [6]. Only people of the AB subgroup lack such antibodies. In humans, besides their expression on red blood cells, ABH antigens are widely expressed on many other cell types, including vascular endothelial cells and epithelial cells of many organs [7]. Importantly, the titers of anti-αGal, anti-NeuGc, and anti-A/B antibodies are highly variable between individuals, ranging from 100- to 1000-fold [8,9]. Using a cellular experimental model, our group showed that the interaction between SARS-CoV S protein and ACE2 could be specifically blocked in a dose-dependent manner by anti-A blood group antibodies when the S protein was synthesized by cells that expressed the A histo-blood group antigen following transfection by the appropriate glycosyltransferases cDNA [14]. These observations suggested that, when produced in cells that express the A or B blood group enzymes, infectious SARS virions are decorated by the corresponding glycan antigens and that the presence of anti-A and anti-B antibodies in blood group O individuals could prevent infection by blocking virus attachment and entry. Moreover, blood group O individuals were at a much lower risk of being infected than non-O individuals in a Hong Kong 2003 SARS hospital outbreak [15], and a similar trend has just been observed for COVID-19 in China [16]. Accordingly, blood group O individuals would be at a lesser risk of being infected than non-O individuals due to blocking of potential transmission events from either A, B, or AB individuals, providing anti-A or anti-B titers are of sufficient magnitude (Fig 1). Because of the natural immune response against these epitopes, the αGal and NeuGc xenoantigens would contribute to prevent cross-species transmission from nonprimate mammals to humans, while A/B blood group antigens would contribute to decrease and slow between-human transmission. Nonetheless, owing to the presence of individuals with low anti-αGal titers, occasional cross-species transmission may occur.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7326345/ Coronaviruses’ sugar shields as vaccine candidates

https://www.nature.com/articles/s41467-020-16567-0 Vulnerabilities in coronavirus glycan shields despite extensive glycosylation 27 May 2020

https://cen.acs.org/biological-chemistry/proteomics/Adding-missing-sugars-coronavirus-protein/98/i16 Adding the missing sugars to coronavirus protein structures Most of the recently reported viral structures have left out the carbohydrate decorations that help mask the proteins from our immune system APRIL 22, 2020

Those sugars can play multiple roles. They stabilize proteins and help them fold up properly. But perhaps they are most important for helping the virus evade the immune system. Glycosylation can act as camouflage because the sugars on viral proteins come from the animal or person that has been infected. Viruses commandeer the enzymatic machinery that host cells use to add sugars to their own proteins and get those enzymes to attach glycans to viral proteins. When a virus infects a human cell, the cell’s ribosome picks up viral RNA and translates it into proteins inside a part of the cell called the endoplasmic reticulum. Cellular enzymes start adding so-called high-mannose, or oligomannose, sugars to newly synthesized proteins as they exit the ribosome. Once synthesized, the proteins travel through the Golgi apparatus to be secreted into the cell. Along the way, those added glycans go through a maturation process in which other enzymes iteratively trim back high-mannose structures and decorate them with other types of sugars to yield complex, branched structures. The more processed the sugars are, the more they look like the host’s own sugars.

[-] TrumpLyftAlles | 2 points | Aug 14 2020 00:14:40

Wow, that's a lot. Thanks for assembling that, stereomatch. Can't say I got much of it. I'm tired. I'll try again later.

Thanks!

[-] stereomatch | 1 points | Aug 11 2020 22:38:50

Very rough transcript starting at the 11:00 minute mark where they discuss ivermectin:

11:00 - discusses ivermectin

medcram - i think it is encouraging - we dont have the randomized blinded clinical trials yet

we were using it in the hospital - still are using it in the hospital

we give it one time - usually that is good for about a week (prophylatically for staff ?)

what the theory is what the virus and the proteins associated with it gets into cell - and into nucleus of cell - which leads to inhibition of the immune response

you may notice covid19 has a long incubation period - sometimes people are asymptomatic - why is that ?

well there is a feeling that the covid19 proteins reduce the immune response from the body

well what happens here is those viral proteins hijack a transportation system in the cell - and this transportation system allows these proteins to get into the nucleus (ie into cell and then further into nucleus of the cell)

what ivermectin does they feel is to shut down that transportation system and prevent the virus from shutting down the immune system

based on the microbiological reasoning that has come out - and there is a plausible mechanism for it

the question is will it work on a randomized controlled basis - but the studies are still pending

but at this point, ivermectin is a medication that has been used for decades

we know the side-effect profile of it

its a relatively safe medication

again the question is do we use it and find out later it did not works - we say oh ok - or do we not use it and find out that it may work or does work and we didn't use it

so I think I'd rather make the first error than the second error

we using:

plasma
remdesivir for those without kidney issues
tocilizumab - IL-6 inhibitor for cytokine storm

different treatments for different stages

early viral replication - remdesivir

and plasma too (for early ?)

and end tocilizumab ideal for cytokine storm

steroid is another thing also looking at (but not using ?)

nutritional support:

zinc
NAC (N-acetylcysteine)
vitamin c
vitamin d

[-] TrumpLyftAlles | 2 points | Aug 12 2020 23:20:18

Thanks so much!

You wondered if ivermectin is for staff. I didn't get that impression. "Good for a week" implies that something happens in the patient (is my guess) and then they re-dose with ivermectin. ?? What do they observe, that indicates the need for another dose? I wish Dr. Seheult had gone into more detail about that. I'm really making up this scenario.

[-] stereomatch | 2 points | Aug 13 2020 17:29:43

WOW, stereomatch, these notes are excellent! I took notes and posted them, then re-read your notes and realized how good they are. Having tried myself, I know how difficult it was. You must have stopped and relistened lots of times -- or you're a much better note-taker than me, highly possible. Thanks so much! You wondered if ivermectin is for staff. I didn't get that impression. "Good for a week" implies that something happens in the patient (is my guess) and then they re-dose with ivermectin. ?? What do they observe, that indicates the need for another dose? I wish Dr. Seheult had gone into more detail about that. I'm really making up this scenario.

Actually I took sloppier notes - after posting the rough transcript here, I relistened to the early part where they talk ivermectin - which is why that part is detailed. The rest is sparse.

The Adam Gaertner transcript is even weaker perhaps because the discussion is sloppier - as Adam Gaertner has a tendency to not complete the thought (since is not a seasoned youtube educator/trainer like medcram/Dr Seheult).

These interviews should get wider coverage - but r/covid19 is for papers, and r/coronavirus may not like youtube links if I am recalling correctly.

[-] TrumpLyftAlles | 2 points | Aug 13 2020 17:52:18

as Adam Gaertner has a tendency to not complete the thought (since is not a seasoned youtube educator/trainer like medcram/Dr Seheult).

Yeah, it's not easy. I wouldn't even try it. My whole life I have struggled with recalling names. It's worse now. Half the video would be me looking up and mutterings "Damn, what's the name?" LOL.

[-] sneakpeekbot | 1 points | Aug 13 2020 17:29:56

Here's a sneak peek of /r/COVID19 using the top posts of all time!

#1: Stanford researchers confirm N95 masks can be sterilized and reused with virtually no loss of filtration efficiency by leaving in oven for 30 mins at 70C / 158F | 1129 comments
#2: Number of people with coronavirus infections may be dozens of times higher than the number of confirmed cases | 1479 comments
#3: At least 11% of tested blood donors in Stockholm had Covid19 antibody as of last week. | 1202 comments

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