This article is part of a public peer review of Scott Alexander’s essay on ivermectin. You can find an index containing all the articles in this series here. I’d like to thank Dr. Avi Bitterman for reading a draft of this and providing feedback. While we don’t necessarily agree on everything I write here, discussing this topic with him has made this a much stronger writeup, so I’m grateful for the time he devoted to talking it through with me.
Of all the articles you have written I think this one is the most transferable to a formal scientific paper.
You have obviously spent an incredible amount of time on this and I think with not much extra work you could truncate this analysis into a publishable paper.
Seriously consider doing this and specifically I would recommend submitting it to the JAMA.
You could maybe even consider offering Scott Alexander and or G M-K to co author. Additionally, if and when you are ready to submit I would very carefully document the process. If nothing else this might make for a good addition to Phil Harper’s Research Cartel documentary if the paper is (more than likely) rejected
The door is open to any person who can contribute to help turn this into a paper. Leaving GMK aside, something like that is the sort of thing that we could have ended up with had we engaged in a dialogue with Scott. Instead, he declined to participate. As such, I find it hard to believe he'd change his mind and re-engage, though my door is always open.
May I ask why you suggest S.A. or GMK as co-authors? They are both adamant on supporting the establishment view that "horse dewormer really doesn't work, except perhaps in patients with worms." That is a far cry from the article here.
You are correct but if the stats and reasoning are sound they should have no problem joining in. Certainly if they do join in then as two prominent voices in the “anti-IVM” camp it would make the paper extremely hard to ignore.
If they reject the offer then they miss the opportunity to be a published author in a high impact journal. Additionally, even though I often don’t agree with their opinions (and attitude) they no doubt know a thing or two about statistics and may even offer some valuable insights into the statistics that Alexandros is missing.
I think at least an offer to co-author is a win-win for Alexandros whether they accept or reject
I agree that they know their stuff, but so do hundreds of other scientists/doctors who could approach IVM in a much more unbiased manner.
I believe SA and GMK cannot and will not approach IVM in an unbiased manner, and their consciences will be clear about wrongfully discrediting IVM now that Paxlovid is available. In other words, it's no longer the case that COVID patients will be dying (even indirectly) due to their disingenuous efforts to discredit IVM.
My guess is that the only way SA and especially GMK would accept co-authorship is if the article is substantially changed to a form of "horse dewormer really doesn't work, except perhaps in patients with worms", perhaps put a little more gently for consolation.
In the link below, Dr. Pierre Kory reviews the suppression of ivermectin research by "prestigious" medical journals. Might be of interest to readers of Alexandros's peer review of S. A.'s post on ivermectin research.
The strongyloides hypothesis also cannot "explain away" the numerous instances of dying COVID patients on ventilators in the UNITED STATES being ultimately saved by ivermectin after their doctors were forced to give it to them by court order, under representation of lawyer Ralph Lorigo:
"Of all the cases I won and the patient was able to go through the full course of ivermectin, the patient is home and healthy," declared Lorigo.
And the stronglyoides hypothesis cannot possibly erase the ENTIRE clinical experience of hundreds of doctors like Marik, Kory, McCullough, etc., in the U.S. and other low-strongyloides-prevalence areas, who all swear that they have seen ivermectin save the lives of many of their COVID patients who were headed straight for death. On the other hand, almost every doctor who opposes ivermectin for COVID does not have one iota of experience using ivermectin in COVID patients.
I think you have to be careful with this argument. ivmmeta.com clearly shows that ivermectin does not work in the later phases. The it seems to work is that it reduces the replication of the virus, preventing the later reaction of immunity system that is so dangerous.
I agree. If ivm works that well in ICU patients (this is a case where the hypothesis by Hazan et al. may be more relevant, but don't quote me, I'm not sure) we'd be seeing much different results. Perhaps there's more to the late administration of ivm, or other factors in play, but just as we wouldn't take 1-2 deaths in a group that ivm administered so late as meaningful, we shouldn't over-emphasize their absence either. My 2c, at least.
I think a way to steelman your argument further would be a method to address the possible, but perhaps hard to pin down, immunosuppressant element in the covid specific data. It does seem you've clearly knocked out the hyper-infection aspect as a direct cause of death to skew the data towards the worm hypothesis as it takes too long and is way too obvious to be missed by doctors who are used to seeing such worms.
I've also drawn the same conclusion that we should use ivermectin and strongly advocate for it in places with high incidents of these worms and yet we find a seeming contradiction where those who think it is a concurrent worm problem do not want to increase ivermectin in places with lots of worms. I describe this as 'the treatment works, but for the WRONG reason'...and we care about the reason something works in a clinical setting or due to the targeting of a co-infection because...why? If it works, it works.
Back to the steelman - I'd think it interesting if you or someone were to look into how badly a variety of worm infections impact the immune system and/or deaths from other diseases. It almost seems to me like the worms are being described with an HIV/AIDS type factor which makes it easier for other things to infect or kill a person, including covid-19.
But is this true? Do we have any reason to believe this? If it is true, do we have any idea how strong such an effect would be? Are people with worms 10% more likely to get other diseases....are they 25% more likely?
Are those diseases worse in severity or mortality and at what rates? Is a preliminary hyperinfection which is 10 days into a 40 day period due to steroid treatment worse than a regular systemic worm infection? I'd think it would be, but to what degree. Can we find studies on hyperinfection in people and if they were getting sick from other things in the early stages...that's a very specific question which may not have an answer in the data, but is worth examining or estimating based on any other parasite and other illness data available....especially since it is being used an 'the' explanation to dismiss ivermectin.
I can see and agree with the intuitive leap that having a low to medium level of worm infection is not good for the body and would have a wide range of negative impacts. But to what degree? The 'worms are the cause of ivermectin working hypothesis' relies heavily on this claim - as hyperinfection has been ruled out as a significant factor...though is non-zero as some people probably did die from hyperinfection.
I'm not sure which other worms or parasitic infections are worth looking into. And there is also the counterargument that some parasites might have no impact or even improve immune function or the body's response to them might improve the immune response to make people less sick. After all, the parasite doesn't want to kill you too quickly or to have you die from other things right away. This could depend on the parasite itself and would likely have some curve to it being beneficial to negligible effect at first and then being terrible for you as you're closer to death.
Mushrooms operate in trees in a similar way, being a mix of a low level parasite or even as symbiotes while the host is health enough to keep supplying them nutrients, then it turns and has a stronger parasitic and negative effect when the mushroom reacts to the host tree's weakening or dying. Or in some cases to a hyperabundance of nutrients or stimulants, such as with the exogenous steroids in humans with worms.
We know that the worm in question here is a long term and hyper-endemic problem and does not routinely kill its hosts, often living within people for years or decades. As such, it seems like there must be some studies out there looking at a variety of worms, and this one in particular, to see its impact on people's health in a wide variety of ways. And then we can evaluate how large or small the immunosuppressant impact from the worms would be.
Do people with worm infections get more flus or colds or other types of infections or diseases which are not covid related? If they do not or do not do so to a significant degree, then we may have little reason to think that ivermectin exacerbates covid infection or symptoms. If we do see higher death or illness rates of those with worms, how strong is the effect? Is there any type of worm count/severity to illness increasing rates which has been observed where a person with a medium level of worms is worse off than a person with a low level of worms, all in comparison to those who are not infected with worms and their general illness rates?
And again about ivermectin...be it an impact on worms, be it direct impact on covid, be it some synergistic drug mixing effect...who cares...a real clinical benefit is what matters and at a minimum the recommendation and usage of ivermectin in places with worms should be a strong takeaway. We have strong evidence it is helping, it rarely to never harms anyone, so why not do it or continue to do it in equatorial places? At the very least the co-benefit of reducing worm infections would be a positive health outcome. I see no downside of any significance, so it makes sense to do it.
Or do research findings only matter if it directly targets a specific disease in a known way which also is useful to treat people in wealthier developed countries? That last point is a bit flippant, but I think holds some truth.
If the situation were reversed and some hypothetical cold climate only parasite, perhaps a foot fungus or something) which was prevalent in colder western countries were the co-factor for ivermectin and using it would clearly help wealthy westerners not die....would there be as much doubt or debate about the hows and whys of a clinically relevant finding of fewer deaths and less illness when ivermectin is used? Would anyone care as much that it appears to be working, but for the 'wrong' reasons, if it was saving Nordic lives instead of Malaysian ones?
Of all the articles you have written I think this one is the most transferable to a formal scientific paper.
You have obviously spent an incredible amount of time on this and I think with not much extra work you could truncate this analysis into a publishable paper.
Seriously consider doing this and specifically I would recommend submitting it to the JAMA.
You could maybe even consider offering Scott Alexander and or G M-K to co author. Additionally, if and when you are ready to submit I would very carefully document the process. If nothing else this might make for a good addition to Phil Harper’s Research Cartel documentary if the paper is (more than likely) rejected
The door is open to any person who can contribute to help turn this into a paper. Leaving GMK aside, something like that is the sort of thing that we could have ended up with had we engaged in a dialogue with Scott. Instead, he declined to participate. As such, I find it hard to believe he'd change his mind and re-engage, though my door is always open.
May I ask why you suggest S.A. or GMK as co-authors? They are both adamant on supporting the establishment view that "horse dewormer really doesn't work, except perhaps in patients with worms." That is a far cry from the article here.
You are correct but if the stats and reasoning are sound they should have no problem joining in. Certainly if they do join in then as two prominent voices in the “anti-IVM” camp it would make the paper extremely hard to ignore.
If they reject the offer then they miss the opportunity to be a published author in a high impact journal. Additionally, even though I often don’t agree with their opinions (and attitude) they no doubt know a thing or two about statistics and may even offer some valuable insights into the statistics that Alexandros is missing.
I think at least an offer to co-author is a win-win for Alexandros whether they accept or reject
I agree that they know their stuff, but so do hundreds of other scientists/doctors who could approach IVM in a much more unbiased manner.
I believe SA and GMK cannot and will not approach IVM in an unbiased manner, and their consciences will be clear about wrongfully discrediting IVM now that Paxlovid is available. In other words, it's no longer the case that COVID patients will be dying (even indirectly) due to their disingenuous efforts to discredit IVM.
My guess is that the only way SA and especially GMK would accept co-authorship is if the article is substantially changed to a form of "horse dewormer really doesn't work, except perhaps in patients with worms", perhaps put a little more gently for consolation.
True but SA has researched this subject more than anybody perhaps apart from Bitterman and Alexandros himself.
A rejection from SA to co-author would be telling in it’s own right.
A co-authored paper which disputes the strongyloides theory would be impossible to ignore. Just a suggestion, Alexandros can do whatever he wants
I don't think you realize how little time SA has put into his essay.
In the link below, Dr. Pierre Kory reviews the suppression of ivermectin research by "prestigious" medical journals. Might be of interest to readers of Alexandros's peer review of S. A.'s post on ivermectin research.
https://pierrekory.substack.com/p/the-criminal-censorship-of-ivermectins?utm_source=substack&utm_medium=email
The strongyloides hypothesis also cannot "explain away" the numerous instances of dying COVID patients on ventilators in the UNITED STATES being ultimately saved by ivermectin after their doctors were forced to give it to them by court order, under representation of lawyer Ralph Lorigo:
"Of all the cases I won and the patient was able to go through the full course of ivermectin, the patient is home and healthy," declared Lorigo.
https://www.theblaze.com/op-ed/horowitz-why-every-red-state-has-an-obligation-to-fight-hospitals-killing-patients-on-ventilators
And the stronglyoides hypothesis cannot possibly erase the ENTIRE clinical experience of hundreds of doctors like Marik, Kory, McCullough, etc., in the U.S. and other low-strongyloides-prevalence areas, who all swear that they have seen ivermectin save the lives of many of their COVID patients who were headed straight for death. On the other hand, almost every doctor who opposes ivermectin for COVID does not have one iota of experience using ivermectin in COVID patients.
I think you have to be careful with this argument. ivmmeta.com clearly shows that ivermectin does not work in the later phases. The it seems to work is that it reduces the replication of the virus, preventing the later reaction of immunity system that is so dangerous.
I agree. If ivm works that well in ICU patients (this is a case where the hypothesis by Hazan et al. may be more relevant, but don't quote me, I'm not sure) we'd be seeing much different results. Perhaps there's more to the late administration of ivm, or other factors in play, but just as we wouldn't take 1-2 deaths in a group that ivm administered so late as meaningful, we shouldn't over-emphasize their absence either. My 2c, at least.
Peter, ivmmeta analyses late treatment and it appears also to show a signal of benefit.
In fact every way the data is analysed there appears to be a signal of benefit
Have a look at the supplementary data on the ivmmeta page
I think a way to steelman your argument further would be a method to address the possible, but perhaps hard to pin down, immunosuppressant element in the covid specific data. It does seem you've clearly knocked out the hyper-infection aspect as a direct cause of death to skew the data towards the worm hypothesis as it takes too long and is way too obvious to be missed by doctors who are used to seeing such worms.
I've also drawn the same conclusion that we should use ivermectin and strongly advocate for it in places with high incidents of these worms and yet we find a seeming contradiction where those who think it is a concurrent worm problem do not want to increase ivermectin in places with lots of worms. I describe this as 'the treatment works, but for the WRONG reason'...and we care about the reason something works in a clinical setting or due to the targeting of a co-infection because...why? If it works, it works.
Back to the steelman - I'd think it interesting if you or someone were to look into how badly a variety of worm infections impact the immune system and/or deaths from other diseases. It almost seems to me like the worms are being described with an HIV/AIDS type factor which makes it easier for other things to infect or kill a person, including covid-19.
But is this true? Do we have any reason to believe this? If it is true, do we have any idea how strong such an effect would be? Are people with worms 10% more likely to get other diseases....are they 25% more likely?
Are those diseases worse in severity or mortality and at what rates? Is a preliminary hyperinfection which is 10 days into a 40 day period due to steroid treatment worse than a regular systemic worm infection? I'd think it would be, but to what degree. Can we find studies on hyperinfection in people and if they were getting sick from other things in the early stages...that's a very specific question which may not have an answer in the data, but is worth examining or estimating based on any other parasite and other illness data available....especially since it is being used an 'the' explanation to dismiss ivermectin.
I can see and agree with the intuitive leap that having a low to medium level of worm infection is not good for the body and would have a wide range of negative impacts. But to what degree? The 'worms are the cause of ivermectin working hypothesis' relies heavily on this claim - as hyperinfection has been ruled out as a significant factor...though is non-zero as some people probably did die from hyperinfection.
I'm not sure which other worms or parasitic infections are worth looking into. And there is also the counterargument that some parasites might have no impact or even improve immune function or the body's response to them might improve the immune response to make people less sick. After all, the parasite doesn't want to kill you too quickly or to have you die from other things right away. This could depend on the parasite itself and would likely have some curve to it being beneficial to negligible effect at first and then being terrible for you as you're closer to death.
Mushrooms operate in trees in a similar way, being a mix of a low level parasite or even as symbiotes while the host is health enough to keep supplying them nutrients, then it turns and has a stronger parasitic and negative effect when the mushroom reacts to the host tree's weakening or dying. Or in some cases to a hyperabundance of nutrients or stimulants, such as with the exogenous steroids in humans with worms.
We know that the worm in question here is a long term and hyper-endemic problem and does not routinely kill its hosts, often living within people for years or decades. As such, it seems like there must be some studies out there looking at a variety of worms, and this one in particular, to see its impact on people's health in a wide variety of ways. And then we can evaluate how large or small the immunosuppressant impact from the worms would be.
Do people with worm infections get more flus or colds or other types of infections or diseases which are not covid related? If they do not or do not do so to a significant degree, then we may have little reason to think that ivermectin exacerbates covid infection or symptoms. If we do see higher death or illness rates of those with worms, how strong is the effect? Is there any type of worm count/severity to illness increasing rates which has been observed where a person with a medium level of worms is worse off than a person with a low level of worms, all in comparison to those who are not infected with worms and their general illness rates?
And again about ivermectin...be it an impact on worms, be it direct impact on covid, be it some synergistic drug mixing effect...who cares...a real clinical benefit is what matters and at a minimum the recommendation and usage of ivermectin in places with worms should be a strong takeaway. We have strong evidence it is helping, it rarely to never harms anyone, so why not do it or continue to do it in equatorial places? At the very least the co-benefit of reducing worm infections would be a positive health outcome. I see no downside of any significance, so it makes sense to do it.
Or do research findings only matter if it directly targets a specific disease in a known way which also is useful to treat people in wealthier developed countries? That last point is a bit flippant, but I think holds some truth.
If the situation were reversed and some hypothetical cold climate only parasite, perhaps a foot fungus or something) which was prevalent in colder western countries were the co-factor for ivermectin and using it would clearly help wealthy westerners not die....would there be as much doubt or debate about the hows and whys of a clinically relevant finding of fewer deaths and less illness when ivermectin is used? Would anyone care as much that it appears to be working, but for the 'wrong' reasons, if it was saving Nordic lives instead of Malaysian ones?
I recall that Haiti in Sep or Oct 2020 initiated a nationwide de-worming drive with Ivermectin. And the people there were untouched by C19.