Haitchpeasauce | 14 points
Anti-COVID-19 efficacy of ivermectin in the golden hamster[-] Haitchpeasauce | 5 points
Abstract
The devastating coronavirus disease 2019 (COVID-19) pandemic, due to SARS-CoV-2, has caused more than 47 million confirmed cases and more than 1.2 million human deaths around the globe, and most of the severe cases of COVID-19 in humans are associated with neurological symptoms such as anosmia and ageusia, and uncontrolled inflammatory immune response. Among therapeutic options, the use of the anti-parasitic drug ivermectin (IVM), has been proposed, given its possible anti-SARS-CoV-2 activity. Ivermectin is a positive allosteric modulator of the alpha-7 nicotinic acetylcholine receptor, which has been suggested to represent a target for the control of Covid-19 infection, with a potential immunomodulatory activity. We assessed the effects of IVM in SARS-CoV-2-intranasally-inoculated golden Syrian hamsters. Even though ivermectin had no effect on viral load, SARS-Cov-2-associated pathology was greatly attenuated. IVM had a sex-dependent and compartmentalized immunomodulatory effect, preventing clinical deterioration and reducing olfactory deficit in infected animals. Importantly, ivermectin dramatically reduced the Il-6/Il-10 ratio in lung tissue, which likely accounts for the more favorable clinical presentation in treated animals. Our data support IVM as a promising anti-COVID-19 drug candidate.
Based on recent evidence on viral load (this study and the recent study from Argentina) it seems ivermectin's primary mode of action is not antiviral. Ivermectin is more likely modulating the immune system, and thus avoiding damage done by the overactive system.
Looking at the results of this article there's a very interesting finding in fig2.b - TNF-alpha in lungs goes to base level with ivermectin! And why is this interesting? The recently released article in Cell points out the worst cytokine damage is done by combination of TNF-alpha and IFN-gamma! So, covid is known to cause damage in lungs, it's known that TNF-alpha is cause of damage, and it's now known ivermectin reduces TNF-alpha in lungs!
Another finding from the article is that the dose wasn't important - 200umg/kg was enough for the response. So, no need for going to extreme doses, and some recent studies seem to point this same out in real life situations.
Now, this is worth repeating. Based on Cell article we know TNF-alpha is likely one of the main causes of severe Covid. Based on this article it seems ivermectin reduces TNF-alpha load in lungs, where covid causes the worst damage. So, there's mode of action right there.
All in all this is very exciting result to me!
[-] stereomatch | 3 points
Are the measurements of viral load based on live culturable viral load, or could be measuring viral debris (as is the case with PCR).
Though I will concede that even a high dead viral (debris) is indicative of high live viral load sometime in the past - when hamster is examined on autopsy. But it is not indicative of current status at death/autopsy.
I say this in the context of the results which Dr Paul Marik points out (also given in MATH+ protocol PDF) that all the live culturable virus is dead by day 8 of first symptoms. Though viral debris remains and can continue to test positive on PCR for months or more.
[-] TrumpLyftAlles | 4 points
Some twitter comments about this study.
Dr. Bakhle's take. I haven't encountered him before, but he has credentials.
[-] Impressive_Run8581 | 3 points
Ice_9 (genius) was not originally an IVM fan due to the short studies (2 hours) (wrong cells, vero vs calu-3) and predicted EC50 calculations he did. He's changed his mind (as all good scientists do) as the data came out. https://twitter.com/__ice9/status/1330647410436136965
[-] TrumpLyftAlles | 2 points
I think he blocked me when I argued about his June 26 tweet. He graciously unblocked me a few weeks ago. He doesn't seem to post about ivermectin often.
[-] Impressive_Run8581 | 3 points
Search his name and ivermectin and there's a good amount now. Most of it recent when the scales tipped.
[-] TrumpLyftAlles | 2 points
Search his name and ivermectin
I didn't realize twitter searches could do that. Too used to reddit's lame search, I guess. Thanks for the tip!
Wouldn't it be sweet if ice_9 had connections at the FDA?
There's someone who twitter pops up occasionally who has involvement managing clinical trials at NIH. IIRC he's an ivermectin skeptic, though.
[-] Impressive_Run8581 | 2 points
https://twitter.com/search?q=ivermectin%20%20(from%3A__ice9)&src=typed_query
[-] Haitchpeasauce | 1 points
Really excellent tweet, he summarises the "flaw" in the original in vitro study and accepts the overwhelmingly positive preliminary data.
The problem wasn't with the Monash study itself, the problem is with media and social media who ran off and drew hard conclusions based on a very early investigational study with clearly stated limitations. From then on it became a dogmatic battle against any new evidence.
Doctors and other people said they wanted to avoid another HCQ debacle. Instead, the cautionary tale of Ivermectin is to not let one bad experience (an anecdote, if you will) taint objective scientific findings.
[-] Impressive_Run8581 | 3 points
Yes he is.
[-] Reddie_Mercury | 3 points
This preprint is from Institut Pasteur in Paris, France. There are some highly-referenced scientists on the author list. IVM will get more attention in the west after this, I presume
[-] Haitchpeasauce | 4 points
I'm so jaded by the West I'm ready for this study to be ignored, and also panned in other subs.
[-] Ok-Film-9049 | 6 points | Nov 22 2020 11:47:27
These animal experiments are the most significant in terms of actual proof of concept. It is much harder for the sceptics to argue about confounders or poor design. Still amazing that IVM is being ignored by most of the world's richest and most educated nations.
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[-] devilslittlehelper | 4 points | Nov 22 2020 12:42:43
You probably mean ““educated””.. /s
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[-] Ok-Film-9049 | 1 points | Nov 22 2020 19:40:06
Yes
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