After clicking to read the middle authors, I saw some familiar names, Pierre Kory being one of them. A doctor that testified to a congressional committee early last year that "the pandemic will end, the economy can reopen, social interactions and activity can resume, and life can normalize" if we simply give ivermectin to everyone.
He has made countless claims like these long before any good research had been done. So he and his organization have a lot riding on proving that ivermectin works for COVID.
What if we take the theory, however outlandish, that Dr. Kory is one of those traditional physicians who, however rare these days, wants want is best for the patients (e.g. lower mortality rate)?
What would be his ulterior motive? there's no money in it for him; ivermectin is dirt cheap and he doesn't produce it. If you think it is all reputational, then it would have been easier and better to salvage his reputation by just admitting his educated guess was wrong if it is in fact wrong, but more research was necessary to prove that. No one would fault him for that, and he knows that.
I think he is just sincerely convinced by the evidence and wants to help tackle the pandemic. He made multiple recommendations some of which got adopted as standard of care (ivermectin wasn't adopted), before any good research was done, simply because that was the best that could be done in a new pandemic. He has got a pretty good track record, even discounting ivermectin
Then again, there are also studies designed to undermine the evidence for off label treatments, such as the one about HCQ that was retracted from the Lancet. So if you are gonna question people's motives then at least question both sides. resistance to ivermectin may also be unscientific in nature. Pharma companies have a lot more riding on mass vaccination than Kory has on ivermectin
I'm given to understand it can be very helpful if you also have worms. It's good at fighting worms, that's what it is, and if you're comorbid with COVID and worms it makes pretty good sense :)
The best meta-study review of Ivermectin I've seen was done by Scott Alexander [0]. He individually reviewed a few dozen studies. His take was that Ivermectin is an effective dewormer that is useful as a prophylactic when people are widely exposed to worms. Because they don't catch worms, they're in better shape to fight Covid when infected. However Ivermectin has no effect in most developed countries where the general population isn't subject to worm infections.
I would also read ivmmeta's response [0] and his reply [1] .
At first I walked away fairly confident at what I had read. Later when I came across the responses, things got more uncertain. The example which quickly comes to mind is that most if not all the prophylaxis studies were not reviewed in Scott's analysis.
Except that ivermectin has been used as antiviral well before the pandemic though. I'm not sure why people assume that doctors tried just random drugs without any rationale behind it!
> Conclusion Our results suggest that co-infection with parasitic co-infection appears to be associated with reduced COVID-19 severity. The results suggest that parasite-driven immunomodulatory responses may mute hyperinflammation associated with severe COVID-19.
> If you don't have worms, ivermectin will not help you
This makes sense and is supported by some data.
> COVID outcomes are better without parasites
This dramatically understates interactions in the immune system. I can go into a longer essay, but:
1) Parasites suppress the immune system (they release chemicals to moderate immune response; otherwise, the immune system would destroy them)
2) There is some evidence that the immune system evolved to operate when suppressed by worms. Autoimmune diseases and allergies may be a symptom of worm-free life.
3) Most of the damage from COVID19 comes from the immune system and not the disease (that's true of most diseases, for that matter).
4) ... and so on.
We have absolutely no idea how ivermectin, worms, and COVID interact. It's too complex a system.
I read this. I am no epidemiologist but it does seem like a pretty weak critique.
The core of this critique is that ivermectin may not have been used consistently among the treatment group, therefore negative results may be masked, or confounding variables may be present.
It seems that ivermectin is generally known to be safe drug for use to treat other antiviral conditions. Is the critic calling that into question? I would expect more evidence for that claim.
Furthermore every science experiment can have confounding variables, so yeah. Even in that case I would expect more of a curious response as 66% reduction in hospitalization at very low p-value is very significant. What could the confounding variables be? Could they be surveyed?
The authors of the article did look into some confounding variables and did find that people more at risk of covid self selected to be in the ivermectin group.
I would like more info about all this. I don't think it's as simple as "bad study move on".
Ivermectin and other anthelmintics (mebendazole, febendazole) are showing quite a bit of promise in cancer therapy. It’s been a while since I looked at it but if I recall correctly at least one mechanism of action is to promote (well, unsuppress) autophagy in diseased cells.
>Brazil’s attorney general is investigating the possible violations of medical ethics and human rights on the recommendation of the National Research Ethics Commission (CONEP), which forms part of the CNS. The trial’s principal investigator, Flavio Cadegiani, was identified in October along with 68 others by a parliamentary inquiry into Brazil’s management of the pandemic as having committed “crimes against humanity.”
Parasitic diseases are highly prevalent in Brazil [1].
Also, as quoted in [2], "Helminth [ie worm] infections are among the most common infectious diseases. Bradbury et al. highlight the possible negative interactions between helminth infection and COVID-19 severity in helminth-endemic regions and note that alterations in the gut microbiome associated with helminth infection appear to have systemic immunomodulatory effects. It has also been proposed that helminth co-infection may increase the morbidity and mortality of COVID-19, because the immune system cannot efficiently respond to the virus; in addition, vaccines will be less effective for these patients, but treatment and prevention of helminth infections might reduce the negative effect of COVID-19. During millennia of parasite-host coevolution helminths evolved mechanisms suppressing the host immune responses, which may mitigate vaccine efficacy and increase severity of other infectious diseases."
It seems strange that the referenced study did not consider the possible confounding factor of parasitic infection.
This still demands investigation. The main issue is that the dosage known to be effective is higher than the dosage known to be safe. It could be that this consistent ongoing use regimen helped by increasing the tolerable concentration or boosting the effects or both.
> the dosage known to be effective is higher than the dosage known to be safe.
This is misleading a little. Only the high dose was tested in cell cultures. That does not mean that low doses are not also very effective.
In the lab, they usually use very high doses to confirm that there is any effect at all. A second set of experiments (not done yet) then calibrate to discover the minimum effective dose.
Cadegiani is part of the "medicos pela Vida" a Brazillian group advocating "tratamento precoce/inicial/integral". The pandemic had an hilarious course in Brazil and there are doctors indicating medicines based on their political views.
Brazil health ministry published an on-line service which suggested HCQ for newborn infants and recently they published a table putting HCQ as better than vaccines.
Beaware of Brazillian studies related to ivermectin and HCQ.
Oh, you mean Cadegiani, the same "crazy person [that] decided to put his patients on every weird medication he could think of [... and] helpfully designated some random patients in his area as a sort-of-control, and then synthetically generated a second control group"[1]? Who would have thought?
> 113,845 (71.3%) regular ivermectin users and 45,716 (23.3%) non-users
> In the absence of contraindications, ivermectin was offered as an optional treatment to be taken for two consecutive days every 15 days at a dose of 0.2 mg/kg/day. In cases where a participating citizen of Itajaí became ill with COVID-19, they were recommended not to use ivermectin or any other medication in early outpatient treatment
> There was a 56% reduction in hospitalization rate (44 versus 99 hospitalizations among ivermectin users and non-users, respectively; RR, 0.44; 95% CI, 0.31-0.63; p < 0.0001). After adjustment for residual variables, reduction in hospitalization rate was 67% (RR, 0.33; 95% CI, 023-0.66; p < 0.0001).
> Missing data from patients were clarified with patients or relatives directly, via phone or in person, by the investigators. Since this is a citywide program, all recorded data must have matched the exact number of COVID-19 cases and deaths of the city.
> An important conservative bias was present. Major risk factors for severe COVID-19 and mortality due to COVID-19, including aging, diabetes, and hypertension, were more present among ivermectin users, which may have underestimated the benefits of ivermectin
The only questionable part of this I can find is a small unfounded semi negative comment about vaccines near the end.
> lack of effectiveness of vaccines in real-life all-cause mortality analyses to date
Vaccines correlate with 5.6x reduction in hospitalization and 12x reduction in ICU cases in Ontario as of today (Jan 22 2022) so not sure where that comes from.
However their results still seem pretty clear that ivermectin helps.
I'm curious if ivermectin and vaccines compound in effectiveness. 2x effective prevention could speed things up a lot.
They don't even know who took ivermectin. The city they studied the ivermectin protocol in had the highest rate of COVID mortalities in the state during the ivermectin protocol. Here's a long Twitter thread shredding this research (read to the end and follow the links, it gets more damning as it goes).
They went to all the trouble to create a huge trial and didn’t make it double-blind, placebo controlled? That is so suspect. We know how to create good experiments, so I just have little trust in bad experiments, especially at this scale.
I don’t care what the outcome is, treatments are treatments. I have no hope for a particular outcome. It’s just bad science. And I might argue bad faith science.
Potential biases: for instance in Brazil there is a very high level of prior Covid infections. What I’d previously infected people were more likely to opt in to treatment bc they are more afraid of reinfection, and the result came from reduction due to prior immunity?
What if people that took the Medecine behaved differently than non-takers?
The authors didn't "create a huge trial". This was just an observational study. While observational studies are less powerful than randomized controlled trials they're not necessarily bad science. Much of our current knowledge in other areas of medicine came from observational studies.
While this study is rather weak and doesn't give us any really definitive results it is a useful data point that can be rolled into future meta analyses.
I'm inclined to agree, but I must ask: Would you have the same standards when it comes to the vaccines?
I'm not aware of any double-blind placebo-controlled trial that is powerful enough to determine risk reduction for death or severe disease in vaccines, much less over several months.
I suggest the real website. Posting NIH Pubmed links tends to be used to suggest the NIH has something to do with it, when this website is just a library catalog of papers. This is a mirror maintained by a government agency.
In this case, the two first authors Lucy Kerr and Flavio Cadegiani are (partially?) funded by Vitamedic, a company that makes Ivermectin. That's not mentioned in the Cureus paper. It is mentioned in some of their papers, like this one: https://www.researchgate.net/publication/357313430_Ivermecti...
They seem to be based in Brazil. Given that intestinal worms are still common in Brazil it may have been that people saw a health improvement in Covid-patients after Ivermectin got rid of the worms.
That quote isn't from the NIH though. Look at the disclaimer:
> This disclaimer relates to PubMed, PubMed Central (PMC), and Bookshelf. These three resources are scientific literature databases offered to the public by the U.S. National Library of Medicine (NLM). NLM is not a publisher, but rather collects, indexes, and archives scientific literature published by other organizations. The presence of any article, book, or document in these databases does not imply an endorsement of, or concurrence with, the contents by NLM, the National Institutes of Health (NIH), or the U.S. Federal Government.
And this is the disclaimer from the publisher:
> The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein.
> Study Group: 223,128 citizens of Itajaí considered for the study, a total of 159,561 subjects were included in the analysis
> There was a 56% reduction in hospitalization rate (44 versus 99 hospitalizations among ivermectin users and non-users, respectively; RR, 0.44; 95% CI, 0.31-0.63; p < 0.0001).
Are you serious? This is such a shitty sample size you might as well be rolling dice.
[+] [-] jjeaff|4 years ago|reply
He has made countless claims like these long before any good research had been done. So he and his organization have a lot riding on proving that ivermectin works for COVID.
[+] [-] galosh|4 years ago|reply
This could describe almost anyone working on COVID over the past 2 years
[+] [-] dionian|4 years ago|reply
[+] [-] refurb|4 years ago|reply
[+] [-] pure_simplicity|4 years ago|reply
I think he is just sincerely convinced by the evidence and wants to help tackle the pandemic. He made multiple recommendations some of which got adopted as standard of care (ivermectin wasn't adopted), before any good research was done, simply because that was the best that could be done in a new pandemic. He has got a pretty good track record, even discounting ivermectin
Then again, there are also studies designed to undermine the evidence for off label treatments, such as the one about HCQ that was retracted from the Lancet. So if you are gonna question people's motives then at least question both sides. resistance to ivermectin may also be unscientific in nature. Pharma companies have a lot more riding on mass vaccination than Kory has on ivermectin
[+] [-] Applejinx|4 years ago|reply
Beyond that, I suspect nah…
[+] [-] ucha|4 years ago|reply
[0] https://astralcodexten.substack.com/p/ivermectin-much-more-t...
[+] [-] disruptalot|4 years ago|reply
At first I walked away fairly confident at what I had read. Later when I came across the responses, things got more uncertain. The example which quickly comes to mind is that most if not all the prophylaxis studies were not reviewed in Scott's analysis.
[0] https://ivmmeta.com/#sa
[1] https://astralcodexten.substack.com/p/higlights-from-the-com...
[+] [-] nikolay|4 years ago|reply
[+] [-] felideon|4 years ago|reply
[+] [-] giardini|4 years ago|reply
[+] [-] ncmncm|4 years ago|reply
The answer is the same: COVID outcomes are better without parasites. If you don't have worms, ivermectin will not help you.
[+] [-] bmj|4 years ago|reply
https://astralcodexten.substack.com/p/ivermectin-much-more-t...
[+] [-] alecst|4 years ago|reply
https://www.medrxiv.org/content/10.1101/2021.02.02.21250995v...
> Conclusion Our results suggest that co-infection with parasitic co-infection appears to be associated with reduced COVID-19 severity. The results suggest that parasite-driven immunomodulatory responses may mute hyperinflammation associated with severe COVID-19.
[+] [-] naasking|4 years ago|reply
[+] [-] blip54321|4 years ago|reply
> If you don't have worms, ivermectin will not help you
This makes sense and is supported by some data.
> COVID outcomes are better without parasites
This dramatically understates interactions in the immune system. I can go into a longer essay, but:
1) Parasites suppress the immune system (they release chemicals to moderate immune response; otherwise, the immune system would destroy them)
2) There is some evidence that the immune system evolved to operate when suppressed by worms. Autoimmune diseases and allergies may be a symptom of worm-free life.
3) Most of the damage from COVID19 comes from the immune system and not the disease (that's true of most diseases, for that matter).
4) ... and so on.
We have absolutely no idea how ivermectin, worms, and COVID interact. It's too complex a system.
[+] [-] francisofascii|4 years ago|reply
[+] [-] xupybd|4 years ago|reply
[+] [-] evgeniysharapov|4 years ago|reply
[+] [-] unknown|4 years ago|reply
[deleted]
[+] [-] tootie|4 years ago|reply
[+] [-] tomlockwood|4 years ago|reply
Seems like this study may have some methodological issues.
[+] [-] srcreigh|4 years ago|reply
The core of this critique is that ivermectin may not have been used consistently among the treatment group, therefore negative results may be masked, or confounding variables may be present.
It seems that ivermectin is generally known to be safe drug for use to treat other antiviral conditions. Is the critic calling that into question? I would expect more evidence for that claim.
Furthermore every science experiment can have confounding variables, so yeah. Even in that case I would expect more of a curious response as 66% reduction in hospitalization at very low p-value is very significant. What could the confounding variables be? Could they be surveyed?
The authors of the article did look into some confounding variables and did find that people more at risk of covid self selected to be in the ivermectin group.
I would like more info about all this. I don't think it's as simple as "bad study move on".
[+] [-] jcims|4 years ago|reply
[+] [-] phonypc|4 years ago|reply
>Brazil’s attorney general is investigating the possible violations of medical ethics and human rights on the recommendation of the National Research Ethics Commission (CONEP), which forms part of the CNS. The trial’s principal investigator, Flavio Cadegiani, was identified in October along with 68 others by a parliamentary inquiry into Brazil’s management of the pandemic as having committed “crimes against humanity.”
https://www.bmj.com/content/375/bmj.n2819
[+] [-] timmytokyo|4 years ago|reply
Also, as quoted in [2], "Helminth [ie worm] infections are among the most common infectious diseases. Bradbury et al. highlight the possible negative interactions between helminth infection and COVID-19 severity in helminth-endemic regions and note that alterations in the gut microbiome associated with helminth infection appear to have systemic immunomodulatory effects. It has also been proposed that helminth co-infection may increase the morbidity and mortality of COVID-19, because the immune system cannot efficiently respond to the virus; in addition, vaccines will be less effective for these patients, but treatment and prevention of helminth infections might reduce the negative effect of COVID-19. During millennia of parasite-host coevolution helminths evolved mechanisms suppressing the host immune responses, which may mitigate vaccine efficacy and increase severity of other infectious diseases."
It seems strange that the referenced study did not consider the possible confounding factor of parasitic infection.
[1] https://pubmed.ncbi.nlm.nih.gov/34105625/ [2] https://astralcodexten.substack.com/p/ivermectin-much-more-t...
[+] [-] srcreigh|4 years ago|reply
For what it's worth, Itajai in southeastern region Brazil has the lowest rate of parasitic infections among the regions at 37%. (your [1])
Probably can't be equated this easily, but 37% could make up a significant chunk of the purported 66% reduction in hospitalizations.
[+] [-] m0llusk|4 years ago|reply
[+] [-] q1w2|4 years ago|reply
This is misleading a little. Only the high dose was tested in cell cultures. That does not mean that low doses are not also very effective.
In the lab, they usually use very high doses to confirm that there is any effect at all. A second set of experiments (not done yet) then calibrate to discover the minimum effective dose.
[+] [-] marcodiego|4 years ago|reply
Brazil health ministry published an on-line service which suggested HCQ for newborn infants and recently they published a table putting HCQ as better than vaccines.
Beaware of Brazillian studies related to ivermectin and HCQ.
[+] [-] felideon|4 years ago|reply
[1] https://astralcodexten.substack.com/p/ivermectin-much-more-t...
[+] [-] weare138|4 years ago|reply
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8765325/
[+] [-] srcreigh|4 years ago|reply
> 113,845 (71.3%) regular ivermectin users and 45,716 (23.3%) non-users
> In the absence of contraindications, ivermectin was offered as an optional treatment to be taken for two consecutive days every 15 days at a dose of 0.2 mg/kg/day. In cases where a participating citizen of Itajaí became ill with COVID-19, they were recommended not to use ivermectin or any other medication in early outpatient treatment
> There was a 56% reduction in hospitalization rate (44 versus 99 hospitalizations among ivermectin users and non-users, respectively; RR, 0.44; 95% CI, 0.31-0.63; p < 0.0001). After adjustment for residual variables, reduction in hospitalization rate was 67% (RR, 0.33; 95% CI, 023-0.66; p < 0.0001).
> Missing data from patients were clarified with patients or relatives directly, via phone or in person, by the investigators. Since this is a citywide program, all recorded data must have matched the exact number of COVID-19 cases and deaths of the city.
> An important conservative bias was present. Major risk factors for severe COVID-19 and mortality due to COVID-19, including aging, diabetes, and hypertension, were more present among ivermectin users, which may have underestimated the benefits of ivermectin
The only questionable part of this I can find is a small unfounded semi negative comment about vaccines near the end.
> lack of effectiveness of vaccines in real-life all-cause mortality analyses to date
Vaccines correlate with 5.6x reduction in hospitalization and 12x reduction in ICU cases in Ontario as of today (Jan 22 2022) so not sure where that comes from.
However their results still seem pretty clear that ivermectin helps.
I'm curious if ivermectin and vaccines compound in effectiveness. 2x effective prevention could speed things up a lot.
[+] [-] tptacek|4 years ago|reply
https://twitter.com/GidMK/status/1471320883461378048
[+] [-] apinstein|4 years ago|reply
I don’t care what the outcome is, treatments are treatments. I have no hope for a particular outcome. It’s just bad science. And I might argue bad faith science.
Potential biases: for instance in Brazil there is a very high level of prior Covid infections. What I’d previously infected people were more likely to opt in to treatment bc they are more afraid of reinfection, and the result came from reduction due to prior immunity? What if people that took the Medecine behaved differently than non-takers?
[+] [-] nradov|4 years ago|reply
While this study is rather weak and doesn't give us any really definitive results it is a useful data point that can be rolled into future meta analyses.
[+] [-] incrudible|4 years ago|reply
I'm not aware of any double-blind placebo-controlled trial that is powerful enough to determine risk reduction for death or severe disease in vaccines, much less over several months.
[+] [-] tamaharbor|4 years ago|reply
[+] [-] kevin_b_er|4 years ago|reply
https://www.cureus.com/articles/82162-ivermectin-prophylaxis...
or the DOI link: https://dx.doi.org/10.7759%2Fcureus.21272
[+] [-] a_bonobo|4 years ago|reply
Here's a weird case on a different paper in the same journal: http://retractionwatch.com/2015/11/02/sex-addiction-article-...
In this case, the two first authors Lucy Kerr and Flavio Cadegiani are (partially?) funded by Vitamedic, a company that makes Ivermectin. That's not mentioned in the Cureus paper. It is mentioned in some of their papers, like this one: https://www.researchgate.net/publication/357313430_Ivermecti...
They seem to be based in Brazil. Given that intestinal worms are still common in Brazil it may have been that people saw a health improvement in Covid-patients after Ivermectin got rid of the worms.
[+] [-] g42gregory|4 years ago|reply
[+] [-] tokai|4 years ago|reply
That is an absolutely egregious misunderstanding of what Pubmed is. Let us not take actions on the basis of misunderstandings by the clueless.
[+] [-] Kenneth21|4 years ago|reply
[deleted]
[+] [-] throwawaymanbot|4 years ago|reply
[deleted]
[+] [-] tamaharbor|4 years ago|reply
[deleted]
[+] [-] mike00632|4 years ago|reply
> This disclaimer relates to PubMed, PubMed Central (PMC), and Bookshelf. These three resources are scientific literature databases offered to the public by the U.S. National Library of Medicine (NLM). NLM is not a publisher, but rather collects, indexes, and archives scientific literature published by other organizations. The presence of any article, book, or document in these databases does not imply an endorsement of, or concurrence with, the contents by NLM, the National Institutes of Health (NIH), or the U.S. Federal Government.
And this is the disclaimer from the publisher:
> The content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein.
[+] [-] tasogare|4 years ago|reply
[deleted]
[+] [-] NikolaeVarius|4 years ago|reply
> Study Group: 223,128 citizens of Itajaí considered for the study, a total of 159,561 subjects were included in the analysis
> There was a 56% reduction in hospitalization rate (44 versus 99 hospitalizations among ivermectin users and non-users, respectively; RR, 0.44; 95% CI, 0.31-0.63; p < 0.0001).
Are you serious? This is such a shitty sample size you might as well be rolling dice.
Why do these studies assume people can't read
[+] [-] sydthrowaway|4 years ago|reply
Do we all have worms and don’t realize it? I say yes.
Should we take ivermectin for quality of life improvements.. is it a medicine or vitamin?
[+] [-] nbzso|4 years ago|reply