Some quick googling doesn’t back this up and my understanding is that ivermectin has only shown itself to be effective at doses that are higher then are remotely safe. It also just isn’t the sort of thing there would be incentive to lie about. Probably then the straightforward story is true no it’s only effective as prescribed as treatment for parasites. If you’d like to provide some sources though or more explanation that would be great.
Note that TMPRSS2 has been a potential target for treating covid basically since the beginning, so some one lying and claiming it as a mechanism of action isn’t surprising
As far as I can tell ivermectin has only been "studied" against TMPRSS2 in silico. The better-studied purported mechanism of ivermectin against SARS-CoV-2 involves something called importin [1]. On the other hand, bromhexine, which is a cough medicine used OTC around the world does inhibit TMPRSS2 and may have action against SARS-Cov-2 [2]. Bromhexine is a prodrug for ambroxol, which is also an OTC cold medicine in much of the world.
Already in 2020 (I forget just how early), __ice9 on twitter was pointing out bromhexine and stressing the importance of blocking both ACE2 and TMPRSS2 binding ("dual-entry inhibition"). This is not an area I personally know about, but it's worth bringing up for the enthusiasts for censorship.
If it works, the OTC nature is important. Hard for any drug to be very effective if the get-an-appointment-see-a-doctor-get-a-prescription-get-it-filled system takes you well past peak viral load before you even start using it.
I have no opinion whatsoever regarding whether or not ivermectin's purported mechanism of action against COVID is valid.
However, this:
> It also just isn’t the sort of thing there would be incentive to lie about
is not true.
There are two incentives to lie about this, if you are in any way associated with drug or vaccine manufacturers.
1.) Ivermectin is out of patent and dirt cheap; basically not profitable at all
2.) Emergency use authorization for the vaccines relied on there being no available alternative treatment
Again, I have no opinion regarding whether or not ivermectin is remotely useful for COVID. But there are plenty of incentives aimed against any older generic being repurposed.
You're discussing incentives that maybe some major drug companies might have, but they aren't the only ones around. I guess, the more accurate position is that there are strong upper bounds to how effective a secretly suppressed drug could be. Imagine that ivermectin just cured covid for a minute. The would be incredibly easy to prove in a study. I mean just observational studies would be glaringly obvious. What ambitious young scientist wouldn't want curing covid on their resume? So you have to believe, either the vast majority of scientists, the press, or government are complicit in this conspiracy and I don't see strong incentives for any of those groups.
Well that's the thing, is that there are literally millions of people in entire countries being prescribed it. India has dished out millions of doses for COVID, and there are many doctors and researchers completely convinced by clinical evidence. It's not as if there are no people picking up a signal, or that no studies are showing utility, it's that the available studies are methodologically questionable. But as you are aware, there are more formal studies taking place at the moment, and the official scientific consensus is that we don't yet know.
Again, my argument against you was that you said that there was no motivation against it, and I said that wasn't true.
> 2.) Emergency use authorization for the vaccines relied on there being no available alternative treatment
That's simply so factually wrong it's tough to take it as serious. having a treatment that might lessen the severity of some percentage of the people that get covid has absolutely nothing to do with a prophylactic EUA for a vaccine that is wildly efficacious against mild and severe covid cases and stop you from getting it in the first place. Let's do a thought experiment even if that were true... that would mean the other vaccines that are under an EUA would have been revoked the moment Pfizer got their full approval which didn't happen. This is "there are naval insignias on the flags therefore we are not a constitutional democracy" level of conspiratorial thinking.
> 1.) Ivermectin is out of patent and dirt cheap; basically not profitable at all
that's the reason they threw it at the virus in the first place. They were looking for anything that might help.
One of the reasons it got looked at was due to a scabies outbreak at Valley View Nursing Home in Toronto that coincidentally had a Covid outbreak at the same time in early 2020. Oddly enough, the residents that had scabies did better than the residents that didn't.
There are more countries in the world than the US and many of them would welcome something like ivermectin if it worked.
Sure, ivermectin is dirt cheap, but that doesn't mean somebody couldn't make a buck off of it. Not to mention that any doctor who actually proved something like that to be effective would be quickly hailed as a hero.
This is the problem with the "Covid Conspiracists"--magically everything is 100% worldwide unified action with perfect lockstep and no deviations--in spite of the fact that many of these countries have primal hatred for one another.
Many countries are using ivermectin...Mexico, India, it's even being prescribed in the US and UK. What it is missing is quality studies, but there are millions of prescriptions being written based off of clinical discretion.
So yes, there are more countries, and many ARE accepting ivermectin for treating COVID. And again, I don't know or care if it works, I'm vaccinated and wouldn't take it, nor am I a conspiracy theorist, your point is just not correct.
Um, exactly? We have millions of scrips issued and still nobody can produce data.
Now, what we can posit is that there is a worldwide conspiracy to suppress the fact that ivermectin is effective OR we can posit that ivermectin doesn't actually work very well for Covid.
The problem with anecdotal medical treatments is that the human organism is highly variable. Just about any disease "treatment" will work for somebody, somewhere. But that's not enough to proclaim that something works. This is going to be especially true in countries where parasitic infestation (which ivermectin does treat) is more common. If a significant fraction of your population got their parasitic infestation cured, their Covid numbers are going to look quite a bit better, too.
If we're trading on anecdotes, then I'll say that ivermectin doesn't work. We had lots of people taking ivermectin at various level in US Red State land. Their hospitals still got overrun. If anything, ivermectin use is correlated with more hospitalization. This is, in fact, a tautology--but not because ivermectin makes Covid worse (or better) but because people were getting poisoned by ivermectin and most ivermectin users were in red state areas which had lower vaccination rates.
This is why you don't believe claims without data.
> And again, I don't know or care if it works, I'm vaccinated and wouldn't take it, nor am I a conspiracy theorist, your point is just not correct.
The problem is that your "I'm just a skeptic" ignores the fact that nobody can cough up any data. Continuing to promulgate things in the absence of data articulates your position quite clearly.
I'm not saying "I'm just a skeptic." People keep putting words in my mouth or arguing against points that I didn't make.
My original argument was against the poster who said that there was no reason to lie about the utility of ivermectin. I said that there was.
In arguing against points that I didn't make, though, you keep making points that I still disagree with. Such as this false dichotomy you keep laying out:
> Now, what we can posit is that there is a worldwide conspiracy to suppress the fact that ivermectin is effective OR we can posit that ivermectin doesn't actually work very well for Covid.
Those aren't the only two options. A third option is that ivermectin does actually have some mechanism of action that has some utility in treating COVID, and that the informal clinical data which continues its usage is because of that. You're acting as if there are formal studies which indicate that it has no utility, but all of the data debunking the utility of ivermectin instead suggests that there is simply not a rigorous study formally demonstrating the utility.
For the third or fourth time, I'm not even saying that I believe that it does have utility. I actually don't care about ivermectin.
> If we're trading on anecdotes, then I'll say that ivermectin doesn't work
I don't remember laying out an anecdote saying that ivermectin does work. An argument was put forth saying that if ivermectin did work, there would be scientists and doctors all over the world studying and using it. I said that there were scientists and doctors all over the world studying and using it. I think it's entirely possible it does nothing and those things could still be true. You're the only one between us who is actually making a claim about the utility of the drug.
> This is why you don't believe claims without data.
I don't know what claim I'm purported to be believing.
But that doesn't incentive say a PHD candidate at Harvard to agree right? They're not making any money from this new startup and they'd probably get a lot of positive news coverage if they could show a cheap cure to covid. Certainly now things are a bit locked in place so it would be harder, there would be some repetitional damage at stake, but I'm just very unconvinced a cabal of biotech startups really has the power to keep a lid on something like this
For what it's worth, that is not an NIH study; it may be listed on PubMed but it appears to be conducted by researchers at the Integrative Biochemistry & Immunology Laboratory, Department of Animal Science, Kazi Nazrul University. PubMed indexes most biomedical literature, not just research conducted by the NIH.
And again, computer simulations suggesting that ivermectin may interact with a specific protein is not the same as saying that it indeed does do so in human tissue.
What is most telling about all of this is that there is no honest discussion. My only initial comment was that this blocks the same protein that ivermectin does. Multiple studies confirm this, its easy to search for them, and it has been the hypothesized mechanism by which ivermectin may show some efficacy.
He's saying that none of these studies have shown in the real world that ivermectin effects TMPRSS2. And I've been trying to have an honest discussion from the beginning. I said I'd failed to find what you were claiming, but tried to make it clear that I was listening if you did have some evidence. Luckily you did, but analyte123 pointed out it was weak.
This paper seems to to be a survey of other papers so doesn't actually provide any new evidence itself. It also has a few grammar issues which makes me more skeptical of it, but whatever. The claim made as I understand it is that there is only very weak evidence that `ivermectin` might effect `TMPRSS2` (aka computer models). Since we've done randomized controlled trials we can be fairly confident that ivermectin doesn't work to treat covid. The best evidence I've heard of for it working came from cell cultures where at very high concentrations it was able to prevent covid from entering cells so maybe the mechanism there even is related to TMPRSS2, but I'm just not really sure of what discussion you were expecting.
Your comment read to me like you see this as vindication that ivermectin is likely to be an effective drug, when it sounds like TMPRSS2 has been consistently targeted as a treatment for covid by a number of different drugs and you've still only shown at best weak evidence that ivermectin even effects it
I am not making any claims of any of these substances effectiveness in treating covid. I'm just pointing out that this substance claims to block the same human protein ivermectin does. We can all make of that what we will.
In political discussions we call this the “anti-anti” position. If you’re not making any claims that Ivermectin works, why are you wasting so much energy and karma attacking those that think it doesn’t work?
The vaccines were authorized under emergency use with trial participants comparable to samples conducted with Ivermectin.
How is it not worth considering for a drug that's already known to be safe to administer and cheap?
Beyond that, there are practicing doctors advocating that they've had good results. This should be more than enough to consider it's use, and not dismiss it as some 'thing of the year to dismiss'.
"The Phase 3 clinical trial of BNT162b2 began on July 27 and has enrolled 43,661 participants to date, 41,135 of whom have received a second dose of the vaccine candidate as of November 13, 2020."
Wow so there was an ivermectin study with 44k people? Where is it?
I agree that it should be able to be studied and probably used. But what's going on is that people are looking for an ALTERNATIVE to the vaccine... which is detrimental when the vaccine is proven to be our best tactic against death/serious illness.
Preemptively, if you're interested in picking apart why one RCT can't be compared in any way to a collection of studies, only some of which are RCTs, I'm not.
> But what's going on is that people are looking for an ALTERNATIVE to the vaccine
*some people
You're effectively strawmanning, and choosing not to engage with the actual doctors who don't advocate this. Which is practically all of the ones I can find. But by all means, please link me all of the doctors stating we should use ivermectin as an alternative. I'll bet I can link a lot more that aren't.
The website I linked above even explicitly states this in bold, on the front page.
>which is detrimental when the vaccine is proven to be our best tactic against death/serious illness.
The trial you're citing seems to indicate there was no observed effect on mortality.
> Wow so there was an ivermectin study with 44k people? Where is it?
There wasn't. Once you eliminate the studies that made up their data it is clear ivermectin doesn't work in the few studies that are left so nobody would bother doing a big study.
> During the blinded, controlled period, 15 BNT162b2 and 14 placebo recipients died; during the
open-label period, 3 BNT162b2 and 2 original placebo recipients who received BNT162b2 after
unblinding died. None of these deaths were considered related to BNT162b2 by investigators.
There was actually one more death in the experimental group, albeit that's not significantly significant.
So some combination of the following must be true:
(1) The vaccination is effective at reducing COVID mortality, but COVID mortality for people in the trial was such a joke that eliminating 95% of COVID mortality doesn't actually change one's risk of dying in a non-negligible manner
(2) The vaccination is effective at reducing COVID mortality, which does spare lives, but it ends up killing just as many from adverse events / side effects
(3) The vaccine isn't effective and they doctored the numbers.
My money is mostly on (1) with a sprinkling of (2), personally.
---
And since people like to be binary thinkers, this is where I mention that I'm not an Ivermectin shill and as a medical nihilist I'm strongly skeptical of treatments in general. And while I haven't looked at the IVM data very much at all, what I have seen is incredibly weak evidence at best, as well as a bunch of really crappy associative arguments from the IVM crowd ("Africa uses IVM and Africa has less COVID mortality than the US!" as if that proves anything)
To quote (slightly paraphrased) the great Jacob Stegenga:
> If we consider the ubiquity of small effect sizes in medicine, the extent of misleading evidence in medical research, the thin theoretical basis of many interventions, and the malleability of empirical methods, then our confidence in medical interventions ought to be low.
>Fun fact: the trial you referenced failed to show any benefit of COVID vaccination in reducing all-cause mortality in the population they studied:
Is the implication that we should have expected it to? The study endpoints are clearly "vaccine efficacy (VE) against laboratory-confirmed COVID-19 and safety data".
I think most people would have expected it to. Whether that's a reasonable expectation or not is up for debate. But yeah, many if not most people in the US were convinced that COVID was a threat so severe that it warranted completely uprooting life as we knew it. A sizeable minority of people are convinced that COVID vaccination is so important that people should be coerced into it by almost any means necessary. So I think understanding that we don't have a single randomized controlled trial that actually shows a reduction in all-cause mortality when given this intervention is pretty important.
It's a general principle of medicine (or at least, it used to be) that the important outcomes are the actually clinically relevant outcomes. Did people die less? Did they achieve a better quality of life? When you get into proxy metrics you get to this weird place where you can show that something is insanely effective for proxy metric X, and yet it makes no difference (or is even deleterious) in thing-you-actually-care-about Y.
This study not finding an effect it wasn't designed to isn't incompatible with the more hyperbolic interpretations of the threat of COVID / the importance of vaccination.
Did we need RCTs demonstrating a reduction in all-cause mortality for polio or measles vaccines before it became blindingly obvious that they were a good idea?
I initially skipped over this post because it appeared to be written in bad faith [1]. But I gave it another shot and read the linked paper, and I agree with the summary. Thanks for pointing this out -- your post has changed my understanding of the vaccine's effectiveness.
For skeptical readers - The linked paper is a medrxiv preprint, with authors from several locations. Many of the authors list affiliations with Pfizer, and the last author is an MD at Pfizer. This seems to be a required report from the ~6-month point of a clinical trial. There really are 14 and 15 all-cause deaths reported in the placebo and treatment groups, respectively. The causes of death for each group are in table S4 [2]. The incidence of COVID in the treatment group is much lower than in the placebo group.
I'm surprised by these results because I would have expected to see significantly lower mortality in the vaccine group.
One possible reason for this surprising result is that only a small fraction of people - even in the placebo group - caught COVID at all. I'm not sure how to account for possible missed infections but Figure 2 of the main text indicates that 0.08% of the placebo group became CASES (which I think means something like "person felt bad enough to see a medical professional, who then diagnosed them with COVID"), and the table in Figure 2 indicates that there were 1034 "occurrences" out of ~22,000 people in the placebo group (which I read as "~5% confirmed infections").
So, it's possible that the beneficial effect of the vaccine is still hidden in the statistical noise since there have been so few infections in the placebo group. It's also possible that some people _were_ harmed by receiving the vaccine (see table S4 [2]), so there's a fixed harm upfront to the vaccine group, which may eventually be surpassed once more of the placebo group gets infected.
Thanks for posting this!
[1] I really do appreciate you making this post, and it helped me learn something. I would have been more willing to read it initially if it had excluded the phrases "such a joke", "since people like to be binary thinkers", "crappy associative arguments", "to quote the great...". It seems like there's a silent majority of HN lurkers that are interested in all perspectives, and really are open to quality arguments like this, but might dismiss this post before reading it because of the choice of phrases.
[meta: this was supposed to be a quick response and then I ended up getting real longwinded]
Glad you got some value out of my comment!
Thanks for the feedback on my tone. In particular the references to specific examples was very helpful to me. I’ll [try to] be mindful of its effect in the future.
Not that it's necessary but just because it's kind of interesting to psychoanalyze, I think some of the tone comes as a [maladaptive] response to past times on HN where I'd go really deep into analyzing certain studies, etc and then would get downvoted or even flagged because the conclusion was that lockdowns were deleterious or that mandates are a bad idea, etc.
The binary thinkers comment specifically (you're right that it will tend to put people off btw) was because in general (not just on HN) it happens all the time that if I point out, say, how we don't even have an RCT that shows a reduction in all-cause mortality from getting COVID-vaccinated, very often I'll get a response to the tune of "Ivermectin doesn't even work you dummy" because most people seem to only have two boxes to put people in (you're either team trump or team biden, team vaccine or team ivermectin, etc). But obviously even if I had done it in a more diplomatic way, making reference to people being binary thinkers is only going to distract from the actual points being made.
I am curious of your mentioning of being offput by "to quote the great...". Did it sound like I was being sarcastic, or was it something else about it? Because I intended it in the literal sense, i.e. indicating my respect for Stegenga and his work.
---
Back to the actual study:
> One possible reason for this surprising result is that only a small fraction of people - even in the placebo group - caught COVID at all. I'm not sure how to account for possible missed infections but Figure 2 of the main text indicates that 0.08% of the placebo group became CASES (which I think means something like "person felt bad enough to see a medical professional, who then diagnosed them with COVID"), and the table in Figure 2 indicates that there were 1034 "occurrences" out of ~22,000 people in the placebo group (which I read as "~5% confirmed infections").
Yes. I suspect that this is partially due to the fact that they actually take some steps to confirm that it really is COVID, whereas in the real world (at least in 2020, but probably still now) they'd run a PCR test with an absurdly high cycle threshold cutoff and then call that COVID even if you were completely asymptomatic (which as an aside is an oxymoron because COVID is supposed to stand for "Coronavirus Infectious Disease", and yet an asymptomatic individual is not diseased (nor are they very infectious btw)). So one interpretation is that when care is taken to actually be somewhat careful about calling something a COVID case, that the prevalence of COVID infection ends up being quite low. Whereas when that care is not taken (whether due to negligence or institutional incentives to drum up case counts / fear in general) you end up with much higher apparent case counts.
This is quite speculative, I know. I'd really like to look at a chart of reported COVID cases in the US versus the rate of cases in this trial. I'd be curious if they are similar shape / relative magnitude, or if there's dramatically more cases in the US in general than the laboratory-confirmed cases in the trial.
I couldn't actually find an actual case definition (maybe it's in the supplement?) but I found this under the Efficacy subheading in the main text:
> BNT162b2 efficacy against laboratory-confirmed COVID-19 with onset ≥7 days post-dose 2
was assessed descriptively in participants without serological or virological evidence of SARS-
CoV-2 infection ≤7 days post-dose 2, and in participants with and without evidence of prior
infection. Efficacy against severe COVID-19 was also assessed.
So I think that means when calculating their overall VE number, they don't "start counting" lab-confirmed COVID-19 until it's been at least a week post second dose. I do know in general in these trials they like to play that game (ignoring infections before the "fully vaccinated" cutoff to get a better-looking VE number). Although Figure 2 seems to provide numbers starting immediately after dose #1 so I suppose those numbers tell us that while VE is quite bad immediately after the first dose, its expected value doesn't seem to be negative (at least in this cohort)
As an aside, I'd note that they blew up the control arm after 6 months, so this is basically the only clean data we're ever going to get. Which should be very concerning to people considering the enormous push to mandate vaccination for an intervention that has never been shown to reduce all-cause mortality in the studied populations.
> So, it's possible that the beneficial effect of the vaccine is still hidden in the statistical noise since there have been so few infections in the placebo group. It's also possible that some people _were_ harmed by receiving the vaccine (see table S4 [2]), so there's a fixed harm upfront to the vaccine group, which may eventually be surpassed once more of the placebo group gets infected.
Unless the data is doctored or has some flaw that I'm not seeing, I agree that a much higher base rate of COVID infection would probably have shown a positive effect on mortality. Which brings us back to #1 of the 3 possible explanations I gave in my original comment. I find it very interesting that actual COVID mortality (or even bad outcomes) were so rare in this cohort of >44,000 people, that a well-over-90-percent-effective-in-reducing-COVID-mortality intervention literally did not make a detectable effect on net mortality. I think from a societal perspective it's quite interesting because during the time this trial was running, people were (and still are btw) getting bombarded by fearmongering, giant red eternally-incrementing "live" death tickers, etc.
It doesn't take some grand conspiracy to see why that might be, but I think it's something interesting to reflect on. It's a large part of why COVID took me from kind of libertarian leaning to full-blown anarchocapitalist, because I am personally so disgusted by what the media, the public health "authorities", and "polite society" at large did in terms of catalyzing such tremendous suffering on a worldwide scale (via the hysteria, global supply chain disruption, missed medical appointments, cancelled elective surgeries, and outright authoritarian/totalitarian public policy), for something that for most people, they would literally never notice if not bombarded about its existence.
The 2019 nipah conference was December 09-10. The first COVID patients with symptoms had only entered the hospital the previous day and the epidemic was still unrecognized. Why was anyone talking about a vaccine for a disease no one knew existed at an unrelated virus conference? Can you source anything to that effect?
Count me in too. I can't stand erosion of society through identity politics and woke'ism. It's on the coverpage of the Economist this week (I am what they refer to as classical liberal): https://www.economist.com/weeklyedition/2021-09-04
Nah is a blanket response to the parent post of hyperbole and faux-objectivity.
His whole post was ridiculous; the GOP has always been just as, if not moreso ready to trade ANYTHING for "security" (security theater mostly), usually if there is a correlating premise of ensuring electoral results in their favor, which they usually beat the Dems over the head with as the "national security" party. With the last half decade of debacles under Trump, the "national security" moniker is arguably up for grabs, but the Dems are half-assed and flailing and the GOP is a viscous joke looking for a punchline (hence why I left the latter to go independent, since the former is a lousy home, even if they aren't a traitorous one).
