Coronavirus | Discussion

I had a first look at the ivermectin 'TOGETHER' study.
Contrary to people who are just after confirmation bias, taking this study as IVM does not work, I am able to assess studies.

As I have posted already "The art of science is now to compare this study to studies where it has a significant effect. To compare the cohorts, the outcome, the endpoints. To think if there might be a rational explanation for the difference, discourse..."
So to 'get' what 'my' assessment is about there has to be scientific discourse. Dose, duration and statistical power (at a pandemic timing also) are all important to talk about whenever you talk about the results of any drug studies. This is common sense.

There is a rule:
If the study design leads to an only small difference between those 2 groups you NEED more power N (more people to be enrolled) to get it statistically significant.
The lesser the difference the more people you need.

I need more time, but it actually showed that ivermectin worked! I mean have a look at figure 2 (superior in 12 of the 15 categories)
It's just isn't statistically significant, would they have enrolled more people it would be.

When they did the study the P.1 variant was dominant. The study is quite old 7 months already!
They gave IVM for 3 days only and started within the first 8 days of symptoms.
This is underpowered for the P.1 variant given 0.4 mg/ kg and only 3 days.

My first remarks:
IVM works best when administered EARLY!
IVM has to be given until symptoms are completely resolved. I did the same mistake and stopped my IVM too early!
Gamma (P.1) was prevalent at ivermectin time which was a significant disadvantage and was not present for the placebo group.

So my first impression: the conclusion "does not work" does not match the results.

 

Either way....

Well, to spot inconsistencies....belongs to 'art'..= " sense of trained ability or mastery of a medium. "

Check this out: (understandable for everybody) just discovered:

There are 679 people in the placebo arm and the same 679 people in the treatment IVM arm, right?
And there are sub-groups which always should add to total amount of participants, right?

In the IVM arm for instance: Again figure 2
<= 50 y 335 persons
> 50 y 295 persons

Together 630 people. WHERE is the rest to 679?
You either are below the age of 50, exactly 50 or above 50 years of age, right?

So if you continue now through all sub-groups and check for the consistency that each should sum up to total of 679 people, you WILL SEE there are even more such missing people.
This distorts any further calculations and relations.

I mean this study has been peer-reviewed and such obvious inconsistency was not found?!?!

Would you have found it?

Body mass index IVM arm:
<30 345 people
>=30 330 people
MISSING: 679-675= 4 people.

Got it?

And so on! 8 Sub-groups all together which do not add to total of 679!

Edit: (some hours later, I am going through it during my actual work here...)
OK next one.
This study is NOT well done! Not even simple sums are right and what's more tragic it passed peer-review despite of obvious inconsistencies!

In the Ivermectin arm we see 624 participants out of 679 completed the study but in the placebo arm only 288 completed the study.

This fact also raises questions why did so many people leave the placebo arm, why have they been disqualified??? This is not 'normal'...it's placebo NOT drug.

If I would be part of the scientific discourse (or even a peer-reviewer myself) I had to email the authors now and ask for clarification.
For today I am tired to check further values myself.......I bet there is more to spot....

 

Never heard such a BS.
To have to live with SARS-COV-2 follows the rules of Epidemiology.
Dunno where to start, is it the association to right wing or the comparison to climate change.
It ever was time to live with covid, so it is with flu.
And mandates either vaccines or masks are more of a right wing ideology than to accept a natural coexistence of virus and human.

To categorize ideas as right or left and then to complain about that they are right or left is nothing but simply poor and a sort of self-evident drivel......it seems it's become common sense to categorize the ideas which one personally does not like as left or right and then to bash on them....
No thanks...you can keep on doing that alone.

To have an idea of to eradicate SARS-COV-2 (which would mean not to have to live with it) is like a stubborn kid that wants ice-cream but the parents say no. The same kids had the idea of zero covid and now there is the price to pay, a naive immune system and mass infections.

Get over it that you sooner or later get covid as well!

It's nothing wrong to wear masks, you can do it, I do not forbid it.
But let me please do the same, making my own decision not to wear one. (no mandates!)
I prefer to live a natural life where I get exposed to natural pathogens in order to have a trained immune system.

Thanks.

 

Another BOLD mistake in the study that actually disqualifies it: This study is botched. If we would deliver such work we would get immense questioning of being professional!

Check it out yourself. It's so obvious that you don't have to be familiar with studies at all.

Figure 1: 228 Were included in the per-protocol analyses.(placebo), right?
This illustrates the study scheme. (flowchart)

Table 2: Placebo per-protocol population Population size 288

bottom table 2:
"and the per-protocol population only those who reported 100% adherence to the assigned regimen."

That means: IT IS crucial to which number you relate. It IS the number of people who completed the study in the placebo arm!!!
Is it 228 OR 288????

Even if it should be a 'typo' this is already peer-reviewed.

What a big mess!

 

Thank god!

Vaccination mandates have just failed here.
The Bundestag did not get the necessary absolute majority.

What's sad is that it has failed because of incompetence to realize vaccine mandates.

It has not failed because of scientific reasons against it (no sterile immunity) and it has not failed because of constitutional rights (experimental stuff, dignity of man, physical integrity etc etc...)

 

That is..IF it is true only a very short period of time true and probably was true and is not anymore.

"Protection by a Fourth Dose of BNT162b2 against Omicron in Israel"
https://www.nejm.org/doi/full/10.1056/NEJMoa2201570

2nd booster only 4 weeks protection against infection.
It follows what one has to expect, exhausting of the immune answer by giving shot after shot.
Protection against severe progresses last till 6 weeks (study end) and probably more.

So what you have said has only evidence for 6 weeks.

Just discovered.
"FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation"
https://www.nature.com/articles/s41586-022-04702-4

What does that mean ...had only a brief look at it so far.....this translates to an effect that is called ADE.
ADE AntibodyDependent/mediatedEnhancement. Is an process where certain antibodies against the virus DO enhance the virulence of the virus. Their attachments to the virus open a way for the virus to be more pathogenic.
So instead of to flag the virus as enemy to be destroyed they provide a mechanism to be more pathogenic.

It (ADE) seem to be a big factor for getting severe. Although authors do not know why some people get it.

During progress of COVID certain antibodies attach to the virus and make them able to infect monocytes (belong to immune cells). They do not replicate there but cause inflammatory death (pyroptosis) and release of potent inflammatory mediators. This can initiate a cascade of inflammatory processes.

 

Well, ADE sounds bad at first sight, yes. Antibodies should cover the virus that it cannot use the entry receptor of a cell anymore (to neutralize the Spike of the virus) AND they should flag the virus to make it attractive for immune cells which are able to eliminate the virus (Phagocytosis) without any ADE effect.

But actually it is 'only' a description of an attribute of the virus. So the 'bad' thing already is that it can kill people.
By this research we get another piece of the puzzle. So the good thing is once we know the mechanism of action completely we can develop approaches / drugs that might interrupt the mechanism (chain).

I did not go through the entire study yet. It takes time. I am only familiar with basics of immunology and inflammatory processes.
I think I have got what they have found (MOA) but need to clarify some details. I need to verify it by a pro at work. When I have done that I can try to explain what happens in detail.

They took blood of people who got severe covid and tried to find what is specific and what is lacking at those without severity. A classical approach.
They took blood of 22 people which were severe (WHO definition, emergency room etc).

ALL them 22 had those special monocytes, around 6% average of all monocytes were affected in all 22 people.

Usually the monocytes take up the virus which is covered with antibodies and eliminate then the virus by Phagocytosis.

The fact that SARS-CoV-2 can infect monocytes due to an ADE effect (monocytes don't have ACE2, ACE2 is the entry receptor of the virus, so naturally SARS-COV-2 cannot enter cells which don't have ACE2 present) was never seen before because such monocytes in question are seemingly not very stable. But this time they took fresh blood which was not frozen before. Frozen blood can destroy them.

It actually was clear a long time ago that at a severe progress it is the own immune system that goes mad triggering huge amount of inflammatory mediators.
The keyword "cytokine storm" was in the news.

I wrote last June:

Interestingly I wrote "mad macrophages" there already.
The study now clarifies what 'mad' is (the sign of this madness they found is inflammasomes) AND they specified monocytes but also mention macrophages. Both are closely related to each others. Monocytes typically circulate through the blood for 1–3 days before migrating into tissues, where they become macrophages or dendritic cells.

So it turns out more and more that severe COVID is actually an auto immune disease as well.

The same seems to apply for long COVID and CFS. But here they found auto antibodies GPCR-AAbs against G-protein coupled receptors. (Remember BC007 that can block those, also blood purification to filter them out).

But what is getting clear more and more it is our own immune system that is responsible for severe covid and long covid in certain individuals. Auto immune disease.