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Ivermectin As a COVID-19 Therapy

I last wrote about ivermectin here, but I’m getting so many question about it that I need to revisit the topic. Although (I’ve said this before), I believe that I will regret doing it, because I expect the signal/noise in the comments section to degenerate to mid-pandemic levels in response.

The mechanistic story here has always been confused, but to be honest, that doesn’t bother me too much. There are a lot of effective drugs whose exact mechanisms we’re unclear about. But keep in mind that if you argue in favor of ivermectin because of its antiviral activity in cell assays, that these levels are far off of what is reached in the reported clinical effects (when there are any – see below). You can’t have both of those arguments working at once: if you build your case on the in vitro results, then you need to regard most of the clinical data as having been dosed at far too low a level to be relevant. I’m not interested in fighting about the mechanism of action, though – the real question is, does it work? If it does, we can figure out how it happens later.

My current opinion is pretty much exactly that of the WHO guidance: I do not think that the current evidence is strong enough to say that ivermectin is a useful therapy for coronavirus patients. I know that there are quite a few studies out there in the literature, but they suffer from various combinations of small sample size, poor trial design, not enough data reported, and (in many cases) inconclusive statistics. I think that WHO page does a solid job of evaluating the literature to that point, and overall, the better the quality of the evidence, the more it tends to show little or no effect of ivermectin.

Since that recommendation in March, nothing has appeared that changes my mind about that.  This study from Egypt compared two groups of about 80 patients in an open-label design, which is certainly not ideal. But it failed to show any statistically significant differences between the treatment group and the controls. This study from Lebanon was more positive: it looked at fifty asymptomatic SARS-CoV-2 positive patients who received a single dose of ivermectin versus fifty asymptomatic age-matched positive controls. The treatment group showed a statistically significant change in cycle threshold when tested by PCR for viral load, indicating a lower viral load. But that goes against the earlier evidence (see the WHO page) that ivermectin treatment had either no effect on viral clearance or (in some cases) lengthened the time needed. This study from Iran was double-blinded, but had only 35 patients in each group. The authors report a shorter duration of symptoms and shorter hospitalization in the ivermectin-treated group, but the statistics for the two groups still overlap, from what I can see.

And this paper, which appears to have come out in time to be included in the WHO guidance, is one of the larger studies. A team in Colombia looked at 200 ivermectin-treated patients and 200 controls with mild coronavirus infections, and found no statistical differences between the two. Objections have been raised to that trial’s use of an oral suspension formulation, I should note.

All in all, though, the most compelling reports of ivermectin’s effects seem to come from the smallest and least controlled samples (all the way down to anecdotal results) while the larger and more well-controlled trials tend to produce equivocal evidence at best. This very much reminds me of the hydroxychloroquine situation, which topic I have no desire whatsoever to revisit. A similar landscape of “the harder you look, the less you see” obtained there, too. And I have to say, there is a passionate constituency for ivermectin treatment, as there was for hydroxychloroquine. I hear from people who are convinced that this is the cure for the pandemic, and they are (variously) baffled that others don’t see it, zealous about spreading the word, or even ready to accuse the vaccine manufacturers and others of actively suppressing this treatment.

But as I said above, I look at the data and I’m not convinced, or certainly not yet (and neither are the WHO reviewers). The only way I can see the reaction of some of my correspondents is if they have been looking at all the most positive reports, accepting them completely and ignoring everything else, and that’s no way to treat the medical literature. This was the case for HCQ as well, I’m afraid. If you haven’t had to mess with drug discovery for a living, it’s understandable that you hear that Some Person Somewhere was very sick, took New Therapy X, and suddenly got better, and then assume that there it is, the cure has been found. But that’s not how it works. Real results stand up when you run larger, better-controlled trials, but most early results don’t turn out to be all that real. Even when this is your job, it’s frustrating to watch this happen, so I can only imagine how baffling it is if you haven’t seen this kind of evaporation before.

And as for the further bunch that are ready to go the conspiracy-theory route, well, as you’d imagine, I’m not having it. As usual, letting that stuff into your head simplifies everything enormously. Things get way too simple, actually. Everything bad is Their Fault, and you’re on the side of the good guys, the angels, struggling against the dark evil forces. It’s a bit like the pre-modern habit of thinking that made someone, every time they come down with some illness or problem, immediately wonder what witch or evil spirit did this to them. Someone has to be to blame, because nothing “just happens”. For the advanced conspiracy theorist, there are no accidents and there are no coincidences: things either directly support the all-encompassing theory, or they just show how the conspiracy is even bigger than it first appeared. It’s non-falsifiable – you can like your favorite conspiracy framework or you can love it, and those are your only choices.

So let me finish up by saying that my mind is not yet made up about ivermectin. I can be convinced by good data; if I couldn’t be, I shouldn’t be doing my day job at all. But I am not too optimistic – the data so far are consistent with a lot of other sorta-kinda-maybe-maybe not things I’ve seen over the years, where if you climb up on the right chair and hold your hand up to your face to block out the exact right stuff then things might look OK, but otherwise not so much. The good data that would dispel this are going to have to be really good, and the longer this goes on the less likely they seem.

168 comments on “Ivermectin As a COVID-19 Therapy”

  1. Akram says:

    Minor correction: “A team in Columbia…” should be “A team in Colombia”

    1. Derek Lowe says:

      Thanks! My right hand puts a “u” in that no matter what.

      1. Akram says:

        Yeah, pretty common mistake.

        Great article though!

        1. Fraud Guy says:

          I’m glad it wasn’t the A-Team in Colombia…

          1. DrOcto says:

            I’d watch the hell out of that though…

    2. Andrew says:

      Spot on!

  2. Masher says:

    Derek – you appear to be a fine scientist (though I’m not qualified to judge!), but on top of that you write so well. Thank you for providing so many clear signposts in the maze of this pandemic.

    1. An Old Chemist says:

      Derek, I have often wondered as to how you manage to write 4-to-5 days per week a scholarly critical analysis of the current hot subjects in pharma/chemistry/science community. You write with authority about varied subjects. I am confused as to how you manage to quickly acquire deep understanding of the diverse underlying concepts. I have wondered if you have got a team of interns helping you, just as the late night TV hosts (comedians, David Letterman, Johnny Carson, Jay Leno) have a team writing their jokes after surfing through day’s news highlights.

    2. Henk Gerritsen says:

      I would say Derek is a fine academist. Science is not about looking at peer-reviewed work only, Einstein even despised peer-review. A fine scientist would be someone like Nobel price winner Ōmura Satoshi, who invented Ivermectin and recommends it against COVID-19. A fine scientist would do research, like prof. Eli Schwartz from Israel, who confirmed that Ivermectin works in his own study. Or like they now do in Spain: https://translate.google.com/translate?sl=auto&tl=en&u=https://beteve.cat/societat/hospital-clinic-prova-eficacia-ivermectina-contra-covid/
      New trial with 800 persons, first results are as effective as only seen with vaccins. That’s science!

      One can state that Ivermectin is probably not working, but how do you explain the data from e.g. New Mexico and India in that case? It’s like telling gravity does not exist without doing research or providing a new theory. It’s also way better to at least do research as stated in the Declaration of Helsinki than to let patient simply die because of a lack of working medicine.

      1. Pablo E Garibotti says:

        The article TALKS that the study shows promisory results. No data

      2. Alberto J. Villena says:

        One of the researchers of such clinical trial says: “ It has long been known that ivermectin has an antiviral effect that is not well studied. The drug inhibits the protein that facilitates the entry of the virus into the cell nucleus to reproduce.”
        But the problem is that the SARS-Cov-2, nor any coronavirus, will enter the nucleus to reproduce. They do proliferate in the citoplasm! So…

      3. nanda says:

        Indeed! He is like a person who writes very well about a country which he has never been because he read a detailed book about it. Only those who have been there – in this cases those who are the ones taking cares of sick people everyday (and not making extra money for that) can really say something about it.

        1. Juan J says:

          Yeah. That’s called anecdotal evidence.

          1. theasdgamer says:

            So is the theory that water is wet–purely anecdotal.

            Science is based on empirical evidence–which includes anecdotes. Control is better until it isn’t, like when lab results can’t be duplicated in the field.

      4. Ricardo Monreal says:

        As always when a treatment is out of patent it is not interesting to the medical community what a coincidence

        1. Big Fool says:

          Like Dexamethasone?

          How come a low-cost steroid that has been shown through clinical trials and through practical application to be successful with Covid patients is never mentioned by the conspiracy theorists?

          Could it be that it doesn’t fit into the Big-Pharma-is-only-interested-in-making-money-on-Covid story line, so it is being ignored and is not allowed to be included in the playbook?

          1. Tristan says:

            I am not going to make any comment about the validity of positive ivermectin studies however I must say that I do not understand this counter argument. Firstly (even considering the second point I will mention in a second) it still took months for steroids to be used to treat the organised pneumonia caused by COVID despite ICU doctors having known about steroids effectiveness against this type of lung damage from very early on. The second point is that whilst yes it is cheap and out of patent it is used during the organised pneumonia stage where the patient has a high chance of dying and so big pharma stands to make little benefit. If they die they can’t take the vaccine later and so they do not care about drugs that only work at the late stages. However when we are talking about something like ivermectin that according to some studies (wether the methodoligical flaws are enough to discredit them is another argument) has a prophylaxis effect considerable to that of vaccines and a good treatment effect that could in combination greatly reduce the need for vaccination or booster jabs for later variants, as well as totally destroy the big pharma antiviral pipelines, then big pharma has a lot to loose. So as you can see your line of reasoning about the use and approval of dexamethasone is flawed.

  3. Spam O'Shanter says:

    Dear Derek,

    Please, please watch Bret Weinstein’s interview with Dr. Pierre Kory on this. I really think you’re pretty catastrophically wrong here. https://www.youtube.com/watch?v=Tn_b4NRTB6k.

    1. Tom Miller says:

      You know no one is going to watch a rambling 2.5 hour video, right? That’s just not an effective strategy for disagreeing to a blog post.

      1. Fraud Guy says:

        I get some people who are very pro-hydoxychloroquine and pro-ivermectin asking me to watch videos. The first few were all talk and no data. I now ask for the studies these people did showing the results, but none of these youtube, gab, telegram, and/or bitchute people produce any. I wonder why.

        1. samuel says:

          You can find many studies on this link including 29 RCT :
          https://c19ivermectin.com/

          1. theasdgamer says:

            He’s just a troll.

      2. Furiously Curious says:

        i hope you didn’t get any knowledge you have, just from reading books dust covers?

      3. Furiously Curious says:

        Merck, (who originally produced Ivermectin) who have been seriously pooh poohing any Ivermectin usefulness, have just announced the US Defence Dept have handed over $1.2 billion, for 1.7 million doses of a new oral anti viral drug called Molnupiravir, to combat covid 19. I am sure they will have spick and span trials that can be lauded.
        Ivermectin is coming in at 83c a dose, and is safe, and has a head start. But no one gets rich.

        1. ravenous bugblatter says:

          Who got rich from dexamethasone?

          1. theasdgamer says:

            Yeah, because the “antiviral” dexamethasone is such strong competition to vaccines.

            Antivirals are competition to vaccines. Dex is not.

            If people believed that early treatment with antivirals was effective to treat covid, they would be less panicked into taking inadequately-tested vaccines.

        2. theasdgamer says:

          Which is why studies will be designed to smear ivermectin.

          It’s an old game that pharma has picked up from the tobacco industry.

      4. Andrew S says:

        Robert W. Malone, the inventor of mRNA vaccines is a guest. It’s a little more than rambling.

      5. Cynthia Freyer says:

        No one? That’s one of those qualifiers that is always wrong. How do I know that’s true in this instance? I’m one of the people who watched the entire vid.

      6. Devon says:

        It’s not “rambling.” Long, yes, but worth the listen if you want accurate information.

    2. MagickChicken says:

      Another “You forgot the steroids!” doctor. Sheesh.

      1. Ken says:

        Steroids? Not zinc?

    3. Elliott says:

      Kory is loudly promoting poor quality results–the sort described by Derek above. There is a detailed takedown of this available by preprint:
      https://www.researchgate.net/publication/351359435_Ivermectin_COVID-19_Miracle_Cure_or_Cruel_Hoax
      (in case anyone is wondering, the conclusion is definitely “cruel hoax”)

      One of his ivermectin papers was rejected from a medical journal after the editors determined that it contained unsubstantiated claims and violated the journal’s editorial policies. Kory yelled that he’s being censored, but that didn’t prevent him from promoting the drug directly to the Trump Administration. There is no peer review or editorial standards on youtube.

      1. Simon V. says:

        Kory’s paper was first peer-reviewed and approved, then by the journal editor’s own admission, they were contacted by a third party to get them to pull the paper. A very unusual action. The paper also had severe internal conflicts resulting from this action and their canning of a special issue on drug repurposing that saw many of their collaborators denounce the paper and swear off of working with it in the future.

        https://www.the-scientist.com/news-opinion/frontiers-pulls-special-covid-19-issue-after-content-dispute-68721

        As to your “takedown”, it is the takedown that is a bad joke and bad science. It shouldn’t suffice to point out a study has biases to dismiss it, you should have to be able to make a cogent argument the biases are significant enough to explain the results of the study away. For example, lack of a placebo in the control group can explain a result showing patients subjectively rate their pain less, or report less symptoms, but they can’t explain a significantly lower mortality rate or a greater rate of viral clearance. If placebo effects could explain 60-70% lower mortality rates, then people should be given sugar pills while being told these are the cure to their condition… because it would be true!

        Dismissing imperfect studies due to the presence of confounders without first evaluating if these confounders are likely to have a significant impact is not smart, rigorous nor scientific. It’s just plain lazy and cowardly. “I can’t be bothered to gauge the impact of confounders, so I’m just going to dismiss it outright”. It’s downright shameful to see how many “scientists” adopt that mindset.

        1. Elliott says:

          Oh, spare me. First, the Kory’s metareview was only “provisionally approved”. Frontiers isn’t saying what made them pull it, but their research integrity team says that they identified “a series of strong, unsupported claims based on studies with insufficient statistical significance, and at times, without the use of control groups.”

          The statement continues: “Further, the authors promoted their own specific ivermectin-based treatment which is inappropriate for a review article and against our editorial policies. In our view, this paper does not offer an objective nor balanced scientific contribution to the evaluation of ivermectin as a potential treatment for COVID-19.”

          The preprint that I cited above goes through the weaknesses of the various studies cited by Kory in detail. Your rant merely amounts to moving the goalposts. “Lack of a placebo in the control group”–really? If you want to see scientific laziness, look in your mirror.

          1. theasdgamer says:

            Without the use of control groups–kind of like the mRNA vaxx studies?

          2. Tracy Ruiz says:

            #1:The author of this article resorted to name calling and baseless accusations of conspiracy theorists to prove his point. This is always a warning sign.
            #2: The author is connected to pharmaceutical companies and is pretending pharmaceutical companies would never do anything to protect or bolster profits. Can you say opioid crisis?
            #3: Can any of you people that are so dismissive against ivermectin explain to me why none of the fancy standards you cited apply to the use of these experimental vaccines without simultaneously making the case for using Ivermectin? ( a known safe drug ) Or are you only good at suspicious takedowns of cheap drugs not under patent that might save lives while never applying ANY of those standards to billions of dollars of federal money to experimental vaccines knowing that mass vaccinations on entire populations during a pandemic can bring about more problems?
            #4: Now I will make some generalizations and do some name calling of my own. Anyone in this comment thread that is bashing the effectiveness of Ivermectin doesn’t want it to work and is connected directly or indirectly to either pharmaceutical companies or science related funding and doesn’t like Ivermectin getting in the way of their agenda. Or you are simply butt hurt because their is an alternative treatment for people that don’t wanna be used as a human guinea pig like you already have been in the biggest experimental treatment in human history. You are saying “I took the vaccine so you should too or you’re a conspiracy theorist “. If you don’t like my gross generalizations, baseless accusations and putting words in your mouth, then welcome to my world. If you want to have a serious discussion about this then maybe you should save all your “smart” comments for a legitimate article that doesn’t resort to name calling and baseless accusations . I give this article as much respect as it deserves which is none. Just another talking points bulletin brought to you by special interest. Maybe with more articles like this, you can create more distrust in institutions and then blame it on everyone else. 👏🏻

      2. theasdgamer says:

        I looked at your link…as soon as I saw it describe “the fiasco of hydroxychloroquine”, I knew it was written by wankers.

        1. David says:

          Because you think that hydroxychloroquine is a success story?

  4. Erik Dienemann says:

    As someone who worked on ivermectin a bit early in my career at Merck, I’d love nothing more than to see ivermectin work for COVID, but I’m similarly unimpressed with the clinical results, overall, and see the same parallels with HCQ. Nice write-up, as usual.

    1. theasdgamer says:

      Did you get fired for incompetence?

  5. AlbellaKutta says:

    Derek – Must echo Masher’s comments on your combination of science and communication (which reflects thoughtful analysis). I have a broader question; at the beginning of the pandemic, I had seen references to a bunch of already approved medications (that had well understood safety profiles and in many case were generic and cheap) that may be repurposed to treat/prevent Covid. The progress on these seem underwhelming; not just because these medications did not work out , but because the studies into these were poorly designed or underpowered. I am thinking about fluvoxamine, bude

    1. Philip says:

      The trial design for many antiviral treatments have been very poor. I would say most are worthless. My pet peeve with the designs are that most start the treatment way too late. Once a person is in the hospital with an acute viral infection, such as SARS-CoV-2, it is past the time when antiviral therapies are most effective.

      Please do not take this as an endorsement of hydroxychloroquine.

      I hope the next time around the FDA will approve rapid antigen testing ASAP, use virus culture as the gold standard, not RT-PCR and get drugs to people in trials very soon after exposure.

      1. Patrick says:

        May I ask why virus culture and not RT-PCR? Is it even more sensitive or does it somehow pick up something different?

        This is 100% a serious question, my impression is PCR is ludicrously sensitive and so I wonder what the purposes/advantages of a culture method are vs PCR? If nothing else, isn’t it hugely more labor intensive and less suitable to massive scale? (I understand if then the suggestion is for more limited use – again, just trying to understand.)

        1. Simon V. says:

          I’m guessing he’s talking about viral culture because PCR tests are so sensitive they can’t tell the difference between live virus and virus fragments the body is shedding from a recent infection. If antiviral therapies are to be useful, they are to be used when there is still live virus in the body, to inhibit its replication until the body’s immune system can kick in, reducing the damage the virus does. Giving therapies that are hypothesized to have antiviral effects to someone with no live virus left is a waste of time… the lack of effect of the therapy may be because the therapy is ineffective, or because it is given too late, you can’t tell which.

        2. Jon says:

          He’s on the “PCR false positive/casedemic” train.

          What people pushing that narrative always ignore is that high CT isn’t always resolved infections. Sometimes that is true, but it can also be:
          – Bad swab/sample
          – Early infection (high CT but decreasing over time)

          Culturing live virus also takes time…typically days. That’s practical if you’re isolating small numbers of people to prevent a new outbreak (using inability to culture virus as a determination of release from quarantine), but it’s not exactly practical from a clinical perspective.

        3. theasdgamer says:

          Jon,

          PCR should not be used clinically unless you can get results very quickly. Even then, it will only tell you if someone has been exposed. Since people are exposed to all kinds of viruses all the time, PCR is worthless when used at high cycling thresholds.

          Viral culturing has to be done if you are doing any kind of research into viral transmission.

          Vaccine efficacy studies, for example.

  6. RAD says:

    I do not think that the current evidence is strong enough to say that ivermectin is a useful therapy for coronavirus patients. I know that there are quite a few studies out there in the literature, but they suffer from various combinations of small sample size, poor trial design, not enough data reported, and (in many cases) inconclusive statistics.

    I’m keeping my mind open about Ivermectin as a treatment during the early replication phase of the disease (when PCR CT values are 24 or less or antigen tests are positive). Timely detection and treatment of COVID-19 before the inflammation phase (7 days after symptom onset) has not received the attention it deserves. Monoclonal antibody and convalescent serum treatments have not looked good in clinical trials for this same reason and they both require intravenous infusion. Ivermectin is cheap oral medication. In TWiV 599 (April 2020) Doris Cully expressed concerns about the dose required to achieve the titres used in the early in vitro studies but the doses used in the real world studies [1] seem reasonable and safe. It is a shame that we don’t have a clear real-world answer to the Ivermectin question at this stage.

    [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088823/

  7. Chris says:

    Is Ivermectin to be used in the Recovery trials?

    https://www.recoverytrial.net

    They seem to give the clearest results.

    1. Druid says:

      I think the Recovery group of trialists are all hospital based and so they have (only) found benefits from anti-inflammatory/anti-immune drugs as they are treating the aftermath effects rather than the infection itself. They have likely prevented thousands of deaths already but I suspect they have not prevented any infection or hospitalization. (They are trialling synthetic neutralising antibodies.) It is difficult to test for prevention of infection, not least because the rate of infection keeps changing. Only vaccines have been poposed for challenge trials and I am not surprised. I guess we could get a handful of enthusiasts of ivermectin to volunteer but what would the control look like? Not placebo for sure, so I think it would have to be a vaccine, and I suspect many of the enthusiasts of ivermectin would baulk at being randomized between that and vaccine. I have worked on antibiotics in the past and there you definitely have to understand the mechanism of action and know very well what the target concentration is, and you have to accept that you will be treating symptomatic patients who already have the infection, not healthy volunteers or symptomless infectees. Recovery is an automated system of randomisation, so if they included ivermectin, it would be up against – among others – dimethyl fumarate, corticosteroids, IVIg, and baricitinib, which I might consider just for the azetidine linker – what fun! But not in a challenge trial.

    2. theasdgamer says:

      Lol, RECOVERY started dosing a mean of 9 days post symptom onset.

      Yeah, they were wonderful for pharma profits, all right. I’m absolutely, positively certain that no money changed hands when RECOVERY was designed. /sarcasm

  8. John Wayne says:

    The usefulness of ivermectin is still up for debate, but I agree with Derek that the trend of results is going in the wrong direction. Are you a doctor that is saying that it works? Show us the data.

    The thing that really defangs the conspiracy part of this is the assertion that doctors aren’t ‘allowed’ to give ivermectin for Covid. In the USA a licensed medical doctor can prescribe any approved drug without having to justify why.

    If you feel like this is important get an internet doctor write you a script for it. Then, buy this cheap and relatively safe drug yourself. You are running on experiment on your own health, but have at it.

    1. Robert says:

      Derek didn’t say the trend was in the wrong direction. He said one result no effect, two results positive, all with methodological shortcomings. One wonders why this even qualifies as an update.

      In fact I went back and read his first post. For someone so obsessed with trials, he doesn’t mention many. This post plus the previous, I count five or six? The meta-analyses I have seen are up to 19 studies that fit this sites apparent thirst for RCTs, though there are many more trials of various types.

      The mere fact that he mentions so few trials ought to demonstrate that he is not presenting the full force of the evidence, but a small sample that is designed to create doubt. Most of his analysis is evaluation of the hypothetical mechanism and not the actual scientific evidence. He traces no trend line; for the trend line, look at the metas, that is what they are designed for. They are overwhelmingly positive.

  9. milkshake says:

    What about fluvaoxamine (Luvox)? – it is a reasonably safe antidepresant with immunomodulatory effect, and the first data (albeit from small imperfect studies) look encouraging, Luvox seems to prevent serious complications and hospitalization

    https://www.covid19treatmentguidelines.nih.gov/immunomodulators/fluvoxamine/

    1. Depressed patients will feel better

  10. Martin says:

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247163
    There are apparently cases when ivermectin is used as prophylaxis once a month. Ivermectin has far too short half-life in human organism to still be active after a month. I could believe in once a week dosing but once a month? That’s bullshit.

    1. Aleksei Besogonov says:

      Yet it works. We likely are missing something in pharmacokinetics of ivermectin. It’s effective in minute concentrations, so it’s not unreasonable to suspect that it might linger for a while.

      1. Martin says:

        Problem is, it must be effective in so minute concentrations or have such a prolonged effect on human physiology or be so slowly excreted and metabolised DESPITE apparent short half-life that it seems unreasonable and even unreal.

      2. Shandyman says:

        Are you implying “water memory” like phenomena?

  11. David E. Young, MD says:

    Those of you who know me understand that I have been making this rant for a long time. I just wish that a year ago (April, 2020, actually) that the NIH fund and conduct a multitude of large studies, with 1,600 to 2,200 participants per study, to be conducted at 200 institutions (picked out of 1,200 institutions that were vetted for research… this would be hospitals already enrolling patients in ECOG and SWOG studies) and done in a randomized, blinded (usual) method. In addition to studies on drugs such as Favipiravir (with well understood anti-viral actions) and Hydroxychloroquine and Ivermectin (with less understood anti-viral actions, if at all).

    I am not convinced that Ivermectin has any merit in the treatment of Covid19. But I also believe in the utility of drug combinations. And even if Ivermectin is weakly active against SARS-Cov-2, it could have a synergist effect when combined with drugs such as Remdesivir, Molnupiravir and Favipiravir. Keep in mind that Favipiravir is easy to produce, as is Ivermectin. If there was valuable activity in such a combination, it could have been massed produced and could have prevented or mitigated a lot of illness back in the summer of 2021. Not just in the US but world wide.

    Granted, carrying on such studies would have been a huge undertaking. I think the biggest obstacles last summer would have been creating a safe environment to have provides see patients with early Covid19 (who are very contagious) and getting people to participate (at a time in history when many people are uncooperative with medical science).

    But I think that such studies should have been done. And so were are still critical of Ivermectin trials and skeptical of it having value. (I am skeptical). But we could have had much for evidence if the NIH had taken the step to find out.

    Now the NIH says that they are sponsoring a 13,500 participant trials to test the utility of Ivermectin and several other repurposed drugs, with the trial starting in July. It seems way to late to do this now (where will they get the participants?).

    That’s my rant….. in a nutshell.

    1. x says:

      “I also believe in the utility of drug combinations. And even if Ivermectin is weakly active against SARS-Cov-2, it could have a synergist effect when combined with drugs such as Remdesivir, Molnupiravir and Favipiravir.”

      Sure. And why not honey and apple cider vinegar? Put the patient under a crystal power pyramid, and while we’re at it, don’t neglect zinc, HCQ and vitamin C! If it doesn’t work, it’s because you didn’t administer the treatment soon enough!

      1. David E. Young, MD says:

        I am not sure of your point. My point was that if Ivermectin were shown to have some activity, that a combination trial would make sense, if combined with another drug that has been proven to be effective, as part of another randomized clinical trial. Do you have a problem with that?

        I would not submit Ivermectin to a combination trial unless a well done randomized trial showed that it had some effectiveness as a single agent.

        I do not see how milk and honey has any part of this discussion.

        1. drsnowboard says:

          “could have a synergist effect when combined with drugs”
          On what basis? The same basis it could be synergistic with milk and honey because dairy farmers and apiarists swear by it?

        2. theasdgamer says:

          I think that you are dealing with trolls.

          Obviously, there are retrospective studies favoring early treatment with various antivirals and we are getting reports from fam. med. physicians that they have treated thousands of patients with only a handful of deaths, which is outstanding. So the bulk of the evidence is to treat high risk patients, tho there is no absolute proof and the evidence may lack internal validity.

          I’m still looking for one fam. med. physician who says that he/she treated patients early for covid with HCQ/ivermecting and gave it up because there was no benefit. I’ve seen IM docs and ED docs say that they tried HCQ and gave it up because they didn’t see benefit to the patients (they treated late, obviously).

          Not one fam. med. doc has said that he/she has tried HCQ/ivermectin without benefit. Not one. No black swan, so the strength of the evidence is for early treatment with antivirals.

          If someone has no ethical problem with providing patients to a RCT testing early treatment with antivirals on high risk patients, RCTs should be done.

          But I don’t think the problem is science-related.

    2. M says:

      I assume you meant “back in the summer of 2020”.

  12. Gus says:

    so its just being reported a rare gene sequence indicates this is an engineered vaccine that leaked – is this true do you think ?

    https://www.wsj.com/articles/the-science-suggests-a-wuhan-lab-leak-11622995184

    1. David E. Young, MD says:

      You meant to say “engineered virus” and not “engineered vaccine”. I have read articles by others scientists who say just the opposite and give counter-arguments to the WSJ article. We will probably never know, but I favor the “comes from bats” hypothesis.

      1. Nick K says:

        No one dispute that the virus originated in Chinese Horseshoe bats. How the virus jumped species to Man is the question. I favour the Lab Leak Hypothesis on the basis of Occam’s Razor (the pandemic started in Wuhan, the only place in China where research on highly pathogenic bat viruses is performed).

    2. Ron says:

      I’ve posted about this before here-and lost the link. In Italy there were blood samples taken from people in mid/late 2019 and frozen. They were recently analyzed and some that were taken in Sept of 2019 showed antibodies to SARS2. That means–those people contracted SARS2 prior to Sept, 2019–perhaps months before the blood draw.
      A recent YT from Dr Campbell showed that Barcelona, Spain had detected SARS2 in their sewer water in early 2019.
      Are these events showing the virus was wild long before Wuhan shutdown?

      1. MrRogers says:

        Or it means that assays can generate false positives.

      2. J says:

        See Derek’s blog on ‘Coronovirus Origins’. I hoped that particular blog by its title would be a prime resource for anyone searching the internet to find a good number of references on origins and I posted various links.

        “Unexpected detection of SARS-CoV-2 antibodies in the prepandemic period in Italy”.
        This would seem to imply that the virus was around in, say, late August 2019 into September 2019.
        https://journals.sagepub.com/doi/10.1177/0300891620974755

        The potential Italian / China link? Suggest the Fashion industry.
        “COVID-19: Did you know about Italy’s China connection”
        “The northern part of Italy has been a traditionally prosperous region due to the flourishing fashion and garment industry. ”
        “A large number of these Italian fashion and garment houses had outsourced their manufacturing to Chinese labour, specifically in Wuhan.”

        1. J says:

          “Coronavirus Origins” – sorry for typo

      3. J says:

        Below is a link to a publication of the paper produced by the University of Barcelona on waste product samples done in March 2019 and at other intervals.
        “Sentinel surveillance of SARS-CoV-2 in wastewater anticipates the occurrence of COVID-19 cases”
        https://www.medrxiv.org/content/10.1101/2020.06.13.20129627v1

    3. KazooChemist says:

      Here is another article that follows the debate about the origin of Covid-19. It seems like a pretty well balanced account that addresses both the scientific and political pressures surrounding the inquiry.

      https://www.vanityfair.com/news/2021/06/the-lab-leak-theory-inside-the-fight-to-uncover-covid-19s-origins

      1. 234 says:

        Now I doubt that even the mutants ( new variants such as triple mutant DELTA] are also china-made! Will they ever be held responsible, and if so, how?

  13. Stuart says:

    Derek – What is your take on the meta analyses out there?

    Kory, P. et al. (2021). Review of the Emerging Evidence Demonstrating the Efficacy of
    Ivermectin in the Prophylaxis and Treatment of COVID-19. To appear in American Journal
    of Therapeutics, May-June 2021

    Hill, A. et al. (2021). Meta-analysis of randomized trials of ivermectin to treat SARS-CoV-2
    infection. Research Square preprint. DOI: 10.21203/rs.3.rs-148845/v1

    Cobos-Campos, R. et al. (2021). Potential use of Ivermectin for the treatment and
    profilaxis. Clinical Research and Trials, 7, 1-5. DOI: 10.15761/CRT.1000333 (over-ridden)

    Bryant, A., Lawrie, T.A., Dowswell, T., Fordham, E.J., Mitchell, S., Hill, S.R. & Tham, T.C. (2021).
    Ivermectin for prevention and treatment of COVID-19 infection: a systematic review and metaanalysis. OSF preprint, https://osf.io/k37ft/ DOI: 10.31219/osf.io/k37ft

    Castañeda-Sabogal, A. et al. (2021). Outcomes of Ivermectin in the treatment of COVID-19:
    a systematic review and meta-analysis. medRxiv preprint, DOI:
    10.1101/2021.01.26.21250420

    Nicolas, P., Maia, M. F., Bassat, Q., Kobylinski, K. C., Monteiro, W. & Rabinovich, N. R.
    (2020). Safety of oral ivermectin during pregnancy: a systematic review and metaanalysis. The Lancet Global Health, 8, E92 – E100. doi: https://doi.org/10.1016/S2214-
    109X(19)30453-X

    Navarro, M. et al. (2020). Safety of high-dose ivermectin: a systematic review and metaanalysis. Journal of Antimicrobial Chemotherapy, DOI: 10.1093/jac/dkz524

    1. David Young says:

      Meta-analyses are of no help if the original studies are flawed. Most of us would ignore this meta-analysis argument.

      None of us know how many small negative studies have been done and not published. Without the results of those negative unpublished studies there can be no meta-analyses.

      1. Stuart says:

        When did Derek say the original studies were flawed? This is what he did say…

        “All in all, though, the most compelling reports of ivermectin’s effects seem to come from the smallest and least controlled samples (all the way down to anecdotal results) while the larger and more well-controlled trials tend to produce equivocal evidence at best.”

        And then you say “None of us know how many small negative studies have been done and not published. Without the results of those negative unpublished studies can be no meta-analyses.”

        So, on the basis of “if the original studies are flawed” – which is not what Derek thinks – and on the basis of studies that we do not know exist we can dismiss the whole thing?

        1. Tom says:

          These meta are typical garbage in, garbage out.

      2. theasdgamer says:

        Flawed, like the RECOVERY trial of HCQ?

        RCTs are no guarantee of external validity or useful testing of a hypothesis. There are so many ways that they can go wrong. A retrospective study may test a hypothesis far better than a RCT (such as giving an antiviral early).

      3. theasdgamer says:

        There are many ways to rig trials.

        1) end a trial early if results are starting to point towards undesired results in order to prevent the results from attaining significance

        2) test the wrong hypothesis

        3) hide delays in treatment while claiming the treatment was early

        4) use PCR with no viral culturing to test viral transmission

  14. Ron says:

    Thanks Derek for posting this. There is not enough money available to have a full RCT. Who is going to fund it—WHO! And at this point, none of the rich nations would have enough people to sign up–they got the jabs. I am a believer, and have used it myself for 3 months before getting the jabs. I had no side effects. Did it keep me from getting Covid19-who knows–but I didn’t and I always felt must safer when using it.

    This is current FLCCC I-MASK+ protocol
    “PREVENTION PROTOCOL
    lvermectin
    Prevention for high risk individuals
    0.2 mg/kg per dose (take with or after meals) — one dose
    today, repeat after 48 hours, then one dose weekly*
    Post COVID-19 exposure prevention2

    0.2 mg/kg per dose (take with or after meals)  — one dose
    today, repeat after 48 hours*
    Vitamin D3 1,000–3,000 IU/day
    Vitamin C 500–1,000 mg twice a day
    Quercetin 250 mg/day
    Zinc 30–40 mg/day
    Melatonin 6 mg before bedtime (causes drowsiness)

    Like most meds–It’s not just the IVM–it’s the other meds which help. The handouts in India, SA, Africa include Vit C and Zinc. It’s the combo.

    A previous comment said “any Dr in the US can prescribe IVM. Good luck finding one. My Dr refused because it was not recommended in our state. He said he would get in trouble–it wasn’t that he thought it was useless or harmful.

    1. Another Guy says:

      I have difficulty understanding the logic of “combination therapy” that follows these premises:
      – drug A does not work
      – drug B does not work
      – drug C does not work
      therefore combining A + B + C must work.

      I guess this is the Twitter-age crowd-sourced and influencer-approved logic.

      1. Robert Clark says:

        Of course, the disagreement is that they ALL do work, but the effect is greater in combination. Using a combination of drugs of course is common in medicine. Look for example at the drugs used for cancer therapy or HIV.

        Robert Clark

  15. David E. Young, MD says:

    There is a fragment of physicians who yield to the temptation to come up with treatment combinations, without any semblance of randomized trials. I mean, you might believe in Ivermectin but where are the compelling evidence that Melanonin, added Zinc, Quercetin and the vitamins contribute to the treatment? None.

    The money is there, but it is nearly impossible to test out every imaginable combination.

  16. In Vivo Veritas says:

    Listen, when the company who MAKES the drug says this:

    No scientific basis for a potential therapeutic effect against COVID-19 from pre-clinical studies;
    No meaningful evidence for clinical activity or clinical efficacy in patients with COVID-19 disease, and;
    A concerning lack of safety data in the majority of studies.

    You can bet that it does not work……

    1. Stuart says:

      Especially when they can still make money from that drug…

      …which they can no longer do with Ivermectin as it is now off-patent.

      Try MK-4482 and MK-7110 (Merck’s new name for CD24Fc, also branded as SACCOVID™).The later is potentially a, “first-in-class recombinant fusion protein that modulates the inflammatory response to the SARS-CoV-2 virus.” Based on interim data, Merck has made deals with the US government for manufacturing and distributing of this drug.

      I’d be more inclined to bet if they didn’t have a much more lucrative alternative to promote.

    2. Stuart says:

      If you are interested in what the drug companies say, how about their former directors?
      Brian Remy Fmr. Director, IP at Gilead Sciences Inc. (Gilead make Remdesivir) recently posted this on Linkedin:

      “It’s simple, use what works & is most effective- period.

      Ivermectin used in combination with other therapeutics is a no-brainer & should be standard of care for Covid-19.

      Other viral infections are treated most effectively with combinations (HIV, HCV, etc.). Thus, there is no reason why ivermectin (with a superb safety profile) should not be combined with other generic or patented therapeutics. For example, as a recommended treatment add-on or formulation, unless there are adverse drug interactions, or legitimate IP/patent business reasons- which would be rare for such an old generic drug.

      The best expert physicians know this & are already doing this (not only with antivirals, but with anti-inflammatories & anticoagulants, with great success, efficacy & safety). For example, see link below:

      https://rcm.imrpress.com/EN/10.31083/j.rcm.2020.04.264

      Everyone should be following their lead and approach.

      Not only would this be good for business & help avoid the criticism, bad PR, & potential civil/criminal liability for censorship, scientific misconduct, etc. etc. for misrepresenting ivermectin & other generics but most importantly it would save countless lives & end this pandemic for good.”

      1. Anon1 says:

        Remy is (was) a patent lawyer. I guess he’s gone full blown conservative Christian. He also believes that the earth was formed in 7 days. He’s also rather young to be ‘former’ anything. I wish him the best of course, but I think he left the science train a while ago.

  17. Mark says:

    One drug or class of drugs, I was kinda looking to hear more on were the 5-alpha-reductase inhibitors.

    I am no tinfoil hat, but a lot of weird coincidences seemed to suggest that they could actually do something. Like males being hit harder, males with androgenic alopecia being hit harder still, people with treated prostatic cancers being under-represented in death statistics, as well as a few reasonable, to my not so trained eyes, studies of the drugs showing effect on mortality.

    I guess my question to anyone is, what ever came of that?

  18. Carol Ann says:

    Maybe someone with more knowledge can answer this – as a lay person who is not associated with the medical field, I would like to know why treatments such as Ivermectin are being dismissed, while the mRNA shots, which I have heard are not proven on humans (hence the EUA situation), are being so widely pushed on ages 12+? I spoke to a pharmacist about ivermectin and the look of fear on her face was evident (surprised me actually). She said she would be disciplined and fired if she advocated for it. My husband’s physician did not even respond to our request for more information on it. There are seemingly a lot of loose ends here, especially when the physicians who we trust to give us straightforward answers are acting dodgy.

    1. exGlaxoid says:

      The mRNA vaccine has been shown in real use in Israel, the UK, and the US to dramatically drop covid rates after about 2-3 weeks in the many million people to get it. There are loads of data to prove that. Anyone who doubts their utility is just ignoring science and reality.

      Ivermectin is well proved to prevent many parasitic diseases, there is no doubt. But it has not been shown in any real scientific studies to have a real effect on covid, although there may be some minor effect. It certainly could have some effect, but clearly does not not have 95% efficacy, like the mRNA vaccines. So smart people should go with the 95% proven efficacy, rather than try to cure the disease after its there with an unknown efficacy.

      1. Furiously Curious says:

        India is showing interesting results that we aren’t hearing about. Massive falls in Delhi, and Mumbai – 90%. Why isn’t this being studied? The Indian media are showing the graphs, while doing their best to not mention Ivermectin. I could consider advertising a factor??
        After the holocaust of stories a few weeks ago, and now with a seeming miraculous recovery, all we hear is crickets.
        Someone mentioned in the comments earlier that there was a blizzard of information on Ivermectin. I’m sorry, hearing anything about it requires more than a little searching.

        1. ravenous bugblatter says:

          Yes, the Indian infection rate is coming down. I think the reason you may not be hearing that ivermectin was responsible for these falls is that there is a far more likely explanation. Correct me if I’m wrong, but isn’t it the case that these falls came a couple of weeks after the Indian government introduced strict lockdown rules? There you go, mystery solved.

    2. Ravi says:

      List of docs , at 5:30 min of video
      https://www.youtube.com/watch?v=7NlF3C9GV8A

      The USA and other Western nations are not allowing a full debate. After all, big Pharma controls the media and FDA.

  19. Bill Cebula says:

    Derek, you have now publicly aligned yourself with the views of big pharma. Congratulations. I hope this comes in handy in your annual raise review with Novartis.

    1. Another Guy says:

      Bill, you can attack Derek all you want, but that doesn’t change science. Medical science is based on evidence gathered from well-designed studies. Unfortunately, Ivermectin is not performing well against COVID-19 in the handful of studies where a meaningful conclusion can be made. That is not surprising since no one has put forth a plausible biochemical mechanism by which it stands a chance of working. There is a chance that it could modulate a yet-to-be-discovered target, however by now we would have seen a strong signal, but the results show the signal is very weak to non-existent. So if I had a limited amount of funding to invest in finding a treatment for COVID-19, I would bet on a candidate that computer modelling showed strong affinity for a known target, etc. etc. In other words, there is no easy way to find effective treatments for new diseases, it has to be earned the hard way. Just like our paychecks.

      1. Bill Cebula says:

        Another Guy,

        This is clearly a foot drag by the US/World health authorities. Why isn’t ivermectin deserved of at least a 2B ( weak recommendation )?

        Based on the population data alone in India ( Goa, Uttarkhand, Karnataka, Uttar Pradesh ), Mexico, and Peru, with case counts dropping dramatically after ivermectin was given to the entire population.

        You don’t need a high level of evidence for a 2B recommendation. I think the population evidence gathered from these countries is more than sufficient. Goa alone has a population of 1.8 million.

        A lay person can understand these facts, and this is why more and more people are going to be talking about it, and wondering why the heck this isn’t part of an official protocol in the United States.

        I know what science is; and an anonymous person on the internet doesn’t have to tell me what they think it is or should be.

        1. David Horner says:

          What population data?

          1. Steffen Grosser says:

            There was e.g. a giant IVM/Aspirin intervention in Mexico City (n>80,000). Everbody got a medical kit once they received a positive test.
            They report a reduced hospitalisation rate by ~2/3.
            The effect was independent of symptom severity, age, etc.– I can’t easily spot the artefact / confounder that could have caused this
            https://osf.io/preprints/socarxiv/r93g4/

          2. Another Guy says:

            The Mexican study used ivermectin, paracetamol and aspirin together in one kit given to persons diagnosed with COVID-19, and the endpoint was reduction in hospitalizations. I’m not surprised that persons given paracetamol and aspirin would feel less symptomatic and not visit the hospital as frequently. Unfortunately there was no control group, and it would have been helpful if they had given a control group only paracetamol and aspirin without ivermectin to control for the possible reduction in inflammation and the need to seek hospitalization. There is also the placebo effect and some of the patients may have simply had not been hospitalized for that reason. If a placebo had been used as a control … you get the picture.

            Unfortunately, these “population studies” are highly methodologically flawed and should not form the basis for country or global-level treatment or prevention guidelines for COVID-19.

        2. ravenous bugblatter says:

          The administration of ivermectin in India coincided with the introduction of strict lockdowns. If you’re looking for confounding factors look no further. Of course the conspiracy zealots won’t mention this.

          1. Robert Clark says:

            This article gives calculation model of how IVM can bind to the ACE2 receptor preventing the SARS2 spike protein from binding to ACE2, the gateway of the virus to the human cell membrane:

            In Vivo
            Sep-Oct 2020;34(5):3023-3026. doi: 10.21873/invivo.12134.
            Ivermectin Docks to the SARS-CoV-2 Spike Receptor-binding Domain Attached to ACE2
            Conclusion: The ivermectin docking we identified may interfere with the attachment of the spike to the human cell membrane. Clinical trials now underway should determine whether ivermectin is an effective treatment for SARS-Cov2 infection.
            https://pubmed.ncbi.nlm.nih.gov/32871846/

            And this article gives a review of the studies on the mechanisms for how IVM can be effective against the SARS2 virus:

            Review Article
            Published: 15 June 2021
            The mechanisms of action of Ivermectin against SARS-CoV-2: An evidence-based clinical review article
            Asiya Kamber Zaidi & Puya Dehgani-Mobaraki 
            The Journal of Antibiotics (2021)
            https://www.nature.com/articles/s41429-021-00430-5

            This article is notable because while it appears in a daughter journal of the prestigious Nature magazine, it takes a positive position on the reports showing IVM effectiveness for EARLY treatment (Table 1).

            Robert Clark

      2. Stuart says:

        “no one has put forth a plausible biochemical mechanism by which it stands a chance of working”

        Dr Mobeen Syed gave this presentation at the International Ivermectin for Covid Conference on the 24th April…

        https://youtu.be/GGIWe5RegVU?t=911

        Are you saying the 6 mechanisms he puts forth are not plausible?

    2. Byrel R Mitchell says:

      Damn. My sister had a headache yesterday, and I suggested ibuprofin. I just realized that I’ve now aligned myself with the Views of Big Pharma vis a vis the effectiveness of NSAIDs.

      Mea Culpa

  20. JimM says:

    Ivermectin is effective against a range of parasites. Parasites are often able to suppress parts of the human immune system, which is why they have shown some benefit in treating some autoimmune illnesses.

    It seems reasonable to guess, therefore, that ivermectin can help some Covid patients whose immune systems are being held down by sub-clinical infections with parasites, but is otherwise ineffective.

    1. Another Guy says:

      Jim, this is a productive line of thinking, science is not dead!

      The challenge in an observation study of patients admitted to hospital with COVID-19 (C19) would be to determine if they had the coinfection before they were infected with C19, sometime during C19 incubation, or after they had severe symptoms. In other words, was the coinfection the cause of severe C19 or an opportunistic infection. If a parasite was shown to be the cause then an anti-parasitic might stand a chance in this sub-group of patients. Note that “subgroup” often turns out to be a very small group of patients, however if it helps them it is worth it. No doubt some readers here will choose to jump to conclusions and choose to believe the parasite theory explains everything, however the facts are that many of the patients in the studies are from countries where parasitic infections are endemic, and we would have expected ivermectin to have a much greater impact than seen so far.

  21. How about an immunosuppressant antibiotic….because often the COVID patients have been treated with antibiotic!

  22. Eric Remy says:

    I have an assignment in one of my classes based around homeopathy, where students have to look up the original sources for a paper I synthesized extolling its wonders. (As you might imagine, I did a lot of *very* selective quoting)

    There’s a classic line in one of the review articles saying something like “Higher quality studies were less likely to show positive effects”. My better students usually end up quoting it back to me.

    Shame really- ivermectin and homeopathic medicines are both cheap and readily available

  23. Ivermectineprobablyhelps says:

    All I see on these articles is cherry picking small RCTs and concluding that there’s not enough evidence.
    The argument here comes down to this for me:
    Study in Mexico city showed 68.4% reduction in hospitalization. That’s on several hundreds of thousands people. https://osf.io/preprints/socarxiv/r93g4/
    Zimbabwe is using it nationally. Look at how they’re doing after their last big wave and deciding to use IVM. Almost nothing, zero. And that’s without vaccines.
    Look at the state of Chiapas in Mexico, they’re using ivermectin and again, almost no cases and deaths. I can’t say that these are absolute definitive proof but can we say that those observations might tend to show that it helps?
    How long until authorities take it seriously and do more testing? What is the downside in administrating a potentially helping drug that is extremely likely not to hurt? We hold it to a much higher standard than currently administrated vaccines or even Remdesivir (on the efficacy side).

    1. David Horner says:

      That mexican study is severely flawed. I wouldn’t be quoting it. My own analysis of their data came to the conclusion that there was no difference between hospitalizations rates.

    2. ravi says:

      The dietary guidelines of US gvt is based on very flawed evidence. But if you allow industry to lobby and sit on decision making bodies, it is considered good science. There are so many cases of FDA approved drugs that cause harm yet allowed to be sold.

    3. Robert says:

      To a certain person, if it isn’t RCT, it may as well not exist. They will block their ears and cover their eyes and say the magic words “give me RCT or give me death.”

      Let us say their was a hypothetical country. All the people were covid positive and on death’ door, they took Ivermectin and got better the next day. Some diehard would still ask, “But was it RCT though?”

      This group is are ideologically committed, and not evidence driven, at least, not when it comes to evidence other than RCT.

  24. anon the II says:

    Your prediction in the second sentence turns out to have been accurate.

  25. C_B says:

    So I’ve got what’s obviously the most important question about this post:

    > “A similar landscape of “the harder you look, the less you see” obtained there, too.”

    Does anybody know what’s going on with this intransitive use of the verb “obtain”? As in, “the following results obtained” rather than “the researcher obtained the following results”?

    It seems to be ubiquitous in science writing (I ran into it a ton in grad school too), but completely unheard-of everywhere else in the English language. Where is this usage from, and why is it only used by scientists writing about science?

    1. Ken says:

      Good question for Language Log (https://languagelog.ldc.upenn.edu/nll/). Their bloggers sometimes take reader submissions.

  26. Someone says:

    The http://www.togethertrial.com will probably settle this debate for good.
    Before that, I can see Ivermectin is not the miracle drug it’s promoted to be, but there *is* enough data showing its multiple MoA against Covid, not only as a mild antiviral but also as immunomodulator. The human studies are not super high quality but the same could be said about the Colombian study mentioned.

  27. samuel says:

    I would like someone to explain to me why there is so much reticence about this drug when in fact some hospitals in India and perhaps in the US are still using Remdesivir, which has been the subject of very few studies, whose benefits are low and which in any case has no effect on mortality and which is not recommended by the WHO.
    For those who are interested in the 29 RCTs on Ivermectin, here is an interesting link:
    https://c19ivermectin.com/

    1. Byrel R Mitchell says:

      Because the evidence around Remdesevir is much higher quality. This trial alone: https://www.nejm.org/doi/full/10.1056/NEJMoa2007764 is substantially stronger evidence about the effectiveness of Remdesevir than we currently have for Ivermectin.

      Generally speaking, low quality studies will show that anything works. There are lots of ways of accidentally getting false positives, and there’s a publication bias: noone really wants to publish a low quality study that found nothing at all.

      However, in the real world, very very few things work. Even among the things we thing should work, only a small percentage actually do. And the proper fusion of ‘lots of low quality studies showing something works’, ‘published low quality studies always show that things work’, and ‘things rarely work’ is ‘this thing probably doesn’t work.’

      Until you get at least one high quality, decent-n study showing an unmistakable positive, effect, the odds are against there being any real effect.

      1. Eric says:

        The link provided by the previous poster shows multiple p<0.001 studies on prevention where some healthcare workers were provided ivermectin and others were not. One of them (Behera et al) had 3500 participants, 2200 on a two-dose regimen and 1100 controls. The results show unadjusted relative risk of 0.18 and adjusted risk of 0.17. Why is this study, and the other hospital worker prevention studies, not a high quality RCT?

        Not a rhetorical question and I don't pretend to have credentials – just trying to understand the debate.

  28. Eric says:

    I’m just a layperson trying to follow the debate. What about the studies when Ivermectin is given as a prophylactic to hospital workers that then show much lower infection rates than a control group? The prevention studies seem to report some strong results, and I understand that this is similar to ivermectin’s use in preventing parasites. It would also be consistent with the apparent success in Indian states that adopted mass dosing.

    1. Steffen Grosser says:

      Yes… it is IMO not untypical of comments like this (Lowe’s) that they just ignore the prophylaxis studies. If they didn’t ignore them, they could no longer claim to be somewhat undecided. The prophylaxis studies have very unequivocal results.

      The prophylaxis studies are either all made up, or IVM works IRL as an effective antiviral.

      (Also, faster viral clearance in infected has been obvserved in *several* in-vivo studies. Some are also RCTs)

      1. Another Guy says:

        RE: “The prophylaxis studies are either all made up, or IVM works IRL as an effective antiviral”

        Lesson learned from the HCQ debacle: people commit scientific fraud for financial gain, megalomania, conspiracy theorist, etc. Refer to: RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis, Lancet, May 22, 2020. It looked scientific enough, it even had forest plots and confidence intervals – very sciency. But it was all made up.

        1. Robert says:

          It is worth pointing out that the fraudulent Lancet study was not in favour of HCQ but showed that HCQ was dangerous. Now why would someone make up data to claim that HCQ was dangerous? Any reasonable answer to that question must posit a conspiracy, however small.

          1. theasdgamer says:

            Reality, people conspire all the time. Bill Gates and Microsoft officers conspired to defraud other technology companies. The tobacco industry funded fraudulent research to boost their claim that cigarettes didn’t cause cancer.

            Now we’re supposed to believe that pharma doesn’t likewise commit fraud?

  29. tt says:

    Wow…these comments didn’t disappoint. Here’s a simple solution for now: wear your mask and get your free vaccine. Long term, let’s continue the hunt for the development of a pan corona virus therapeutic or prevention. Thusfar, Derek’s 100% that there is no compelling evidence that gives even a glimmer that Ivermectin works, unless you are the type who has a conclusion and only cherry picks studies that support it and ignores those that don’t. By all means, keep an open mind as to its efficacy, but usually stuff that works well shows a strong signal and, to date, nothing demonstrates that. This is just starting to feel like the HCQ silliness all over again and it’ll suck attention, time, money, and maybe lives away from more valuable research studies (de novo drugs, combos, improved vaccines). The part that I truly can’t wrap my head around is the strong correlation between right wing conspiracy nuts and these alternative, repurposed treatment proposals (HCQ/Zinc/Ivermectin/bleach).

    1. Eric says:

      Not everyone in the world has the luxury of an available free vaccine. Even those that do might need a backup therapy depending on how future variants turn out. The evidence for Ivermectin is far greater than HCQ. You can look at the https://c19ivermectin.com/ list and compare to the HCQ list and it’s a night and day difference.

  30. richard moore MD says:

    Look at the plot of cases from Uttar Pradesh, India, one of the most densely populated states on earth. Note the Recent abrupt rise and fall of cases. Something has caused a fall in cases and deaths and it is not vaccines or social distancing or masks.
    ‘Who’s that sneaking round the corner,
    Might it be Mack the…’ Ivermectin
    What gets me about this chin pulling nay saying on ‘experts’ parts is people are dying from the disease and countries are disrupted way more than we here in the USA are.

    https://www.google.com/search?q=coronavirus+uttar+pradesh&ie=UTF-8&oe=UTF-8&hl=en-us&client=safari

    1. ravenous bugblatter says:

      The downturn of cases in Uttar Pradesh followed the introduction of measures by the local government including increased testing and a curfew in mid to late April. Occam’s razor says there’s no need to invent a miracle drug to explain this.

      https://indianexpress.com/article/cities/lucknow/uttar-pradesh-imposes-night-curfew-in-10-dists-with-more-than-2000-active-cases-7275574/

      1. theasdgamer says:

        Occams’ razor has nothing to do with your fairy tales.

        Masks and social distancing are as helpful as rabbits feet.

        1. David says:

          It’s a waste of time to think that you have some data to back up your statement, isn’t it?

          I keep waiting for you to make your case like a grown-up, presenting supporting data and not negating any data point that doesn’t. Is that too much to ask?

  31. mike99588 says:

    The problem with the usual EBM paradigm here is that big “high quality” studies typically have serious deficiencies (e.g. deliberately/wildly wrong dosage, formula and/or schedule) are over weighted and important secondary data that would permit more accurate analysis and modeling is hidden or omitted. A very common scam in “mainstream”/marketing attacks with MDs/PhDs on cheap generics that accounts for a lot of Derek’s “evaporation” in controversies. I think a less passive term, like (deliberately) “vaporized” is would be more accurate.

    In essence, spiked tests “disproving” a medicine or treatment, that when correctly analyzed would be merely confirmation how not to do it either already known to the experienced hands, or easily predictable with an intuitive science based model. Their proper placement is merely a foot note to corruption or incompetence in a 3D plot.

    The IVMmeta.com site stratifies the data into prophylaxis, early treatment and late treatment, a good start. Once these prophylaxis data are modeled for dose/blood levels (<150-400 mcg/kg or BSA) and interval (e.g. 3-30 days, or only once) the data become highly predictive of other datasets such that reasons for failures are obvious; and high dose, high frequency appears to drive predictions for 99+% efficacy against disease for individuals with varied initial comorbidities.

    1. Jacob Kelter says:

      This comment deserves a reply. https://ivmmeta.com seems to have done a very careful analysis of all the available studies and I haven’t found any detailed rebuttals from experts yet.

  32. les christianson says:

    for interested parties, get onto youtube and look up brett weinstein / pierre kory and listen to the 2 hr 30 min podcast. using ivermectin is solid/appropriate.

  33. Whapto says:

    Dr Mathews says Ivermectin has no proven role in curing COVID. Is that true?

  34. JRK says:

    Recently published meta-analisys. It destroys the lies that there is only tiny RCTs and that all are low quality.
    https://onlinelibrary.wiley.com/doi/10.1002/rmv.2265

    1. Another Guy says:

      Thank you JRK for alerting us of this new meta-analysis. It is helpful the authors show the PRISM diagram of how the literature search was filtered down to the selected studies and here we 19 RCT studies included in the meta-analysis. Table 3 shows most of these studies were judged of moderate quality (the author’s judgement, not mine) meaning some did not have adequate double-blinding, or randomization. Regarding figure 2, notice how the each of the plots have different studies and not the same 19 studies in each sub-plot. The likely reason is the studies are not very comparable and get filtered down to a handful when looking at any particular outcome. This meta-analysis confirms there are only a small number of RCTs and the quality is not great.

      The meta-analysis paints a picture that ivermectin has pan-antiviral activity and includes many references, however as the Caly study quoted therein shows, micromolar levels of ivermectin were used in the in-vitro assays, translating to serum levels that are 100’s of times higher than currently used to treat parasitic infections in humans. This is impractical and likely will lead to serious adverse events.

      Basically we are no further ahead on this issue as before. Ivermectin may benefit some patients with COVID-19 under certain conditions, however we are not certain what those conditions are. IMO ivermectin should not be used at a population level to treat COVID-19. Possibly some groups of patients could benefit, and more work needs to be done to determine the characteristics of these patients including coinfections with parasitic infections or other conditions that may facilitate treatment with ivermectin where the mechanism of action is plausible.

  35. Robert says:

    This post exists to discourage Ivermectin and not to present a balanced presentation of the evidence. For objectivity or simple logic, look elsewhere.

    This is clear since it does not mention or discuss the numerous meta-analyses. These must be discovered in the comments section. The point of metas is that they cancel out methodological shortcomings, within reason.

    Your point of only a few studies on each outcome is a textbook example of not seeing the forest for the trees. A few studies showing improvements in each different outcome is evidence of a drug that has broad benefits and cannot be discounted so easily.

    In both cases metas present a type of evidence that cannot be discounted by saying this or that study didn’t move me.

    Your comment that a dose 100s of times higher (of a manifestly safe drug) will be harmful is not held to the standard of evidence you seem to apply to others. The fact is that the 100s of times higher dose has actual evidence in the form of studies (the very studies in question) that have improved Covid outcomes, while your claim is wholly without evidence and is speculation.

    1. Another Guy says:

      The patients were not given 100X ivermectin, they were given close to the standard human dose. One of the papers (Ahmed 2020) cited used 12mg ivermectin once a day for 5 days. This is very similar to the dose used in human adults to treat parasitic infections.

      RE meta-analyses: they follow the garbage-in, garbage-out principle. A million bad studies run through a meta-analysis won’t magically produce good data. RCTs remain the gold standard, and the meta-analysis of several high-quality RCTs with very similar study design and populations would be expected to trump any single RCT, however there is a big caveat in that the studies must be high-quality RCTs and very comparable. We simply aren’t seeing that standard met in these ivermectin meta-analyses.

      I don’t have time to do the “ivermectin-for-all” camp’s homework, and I’m done commenting further. Thank you to all those who provided constructive insights.

      1. Robert says:

        In that case I’m really not sure what point you were trying to make in your initial post about 100x doses being “impractical and leading to adverse events.”

        You have not even alleged that the studies in the meta analysis were “garbage”. You merely say they were of moderate quality and some did not have double blinding or randomisation. Therefore, it is more a case of “moderate evidence in, moderate evidence out.”

        Moderate evidence is evidence. There are many types of evidence that do not fit the RCT model. To be blind to them is to lose touch with reality. “RCT or nothing” should not become a religious dogma that leaves you blind.

        I encourage everyone to look at these mat-analyses themselves. Simply look at the studies they contain. The comments of Derek Lowe and Another Guy in no way do justice to the weight of evidence.

        No one is asking you to do anyone else’s homework.

      2. Trebich says:

        “RCTs remain the gold standard, and the meta-analysis of several high-quality RCTs with very similar study design and populations would be expected to trump any single RCT, however there is a big caveat in that the studies must be high-quality RCTs and very comparable. We simply aren’t seeing that standard met in these ivermectin meta-analyses.”
        You say.
        Where are the RCT studies showing effectiveness and no adverse effects of masks and 6 feet distancing, shutdowns of entire industries, ruination of half the country, etc…
        There are none, but you shill for your f..ing “vaccine”. The day of the pillow is coming!

      3. theasdgamer says:

        I just published about RCT’s as evidence on my blog.

        tldr: RCTs are useful because of internal validity, but require supplementation with methodologies that add external validity. It’s not either/or. We know historically that retrospectives have found problems missed by RCTs.

    2. ravenous bugblatter says:

      I think the 100x comment refers to the dose predicted to reach an effective anti-viral concentration in the lung based on the in vitro studies. Dosing any drug 100x higher level than its previous highest dosed level outside a monitored clinical trial setting would constitute an experiment on the public that would not be permitted by most national regulators. I’m surprised if anyone here would be defending that.

      I think the Indian public were given the approved anti-parasitic dose. At this dose the in vitro data suggests it should be ineffective against Covid so this seems more an act of desperation and not very ethical in my opinion, as there are rare side-effects.

  36. Wallace Grommet says:

    I didn’t get cured of Covid by taking Ivermectin, but my penis girth increased two inches.

  37. PRESS RELEASE

    May 26, 2021

    INDIAN BAR ASSOCIATION SERVES LEGAL NOTICE UPON DR. SOUMYA SWAMINATHAN, THE CHIEF SCIENTIST, WORLD HEALTH ORGANISATION

    A legal notice is served by Indian Bar Association (IBA) upon Dr. Soumya Swaminathan, the Chief Scientist at the World Health Organisation (WHO) on May 25, 2021 for her act of spreading disinformation and misguiding the people of India, in order to fulfil her agenda.

    The notice is based on the research and clinical trials carried out by ‘Front Line COVID-19 Critical Care Alliance’ (FLCCC) and the British Ivermectin Recommendation Development (BIRD) Panel, who have presented enormous data that strengthen the case for recommendation of Ivermectin in prevention and treatment of COVID-19.

    Dr. Soumya Swaminathan has ignored these studies/reports and has deliberately suppressed the data regarding effectiveness of the drug Ivermectin, with an intent to dissuade the people of India from using Ivermectin.

    However, the Indian Council for Medical Research (ICMR) and All India Institute of Medical Sciences (AIIMS), Delhi have refused to accept her stand and have

    retained the recommendation for Ivermectin under ‘May Do’ category, for patients with mild symptoms and those in home isolation, as stated in ‘The National Guidelines for COVID-19 management’ last updated on May 17, 2021.

    In order to stop Dr. Soumya Swaminathan from causing further damage to the life of citizens of this country, IBA has decided to initiate legal action against her and as part of the process, a legal notice has been served upon her.

    P.S. IBA has observed that the content of several web links to news articles/reports included in the notice served upon Dr. Soumya Swaminathan on May 25, 2021, which was visible before issuing the notice, has either been removed or deleted now.

    IBA had anticipated this and therefore we have downloaded soft copies of these news articles before issuing the legal notice. It is ludicrous on part of the forces resorting to such cowardly acts, for they do not know that they are providing very strong evidence of their desperate attempt at blocking information/news regarding Ivermectin.

    Adv. Nilesh C. Ojha
    National President Indian Bar Association
    http://www.indianbarassociation.in

  38. John Stephenson says:

    I suppose this is fake news as well this is the biggest cover up in human history on a global scale Big Pharma companies & Billionaires e.g. Bill Gates who invested heavily in Pfizer & WHO controls everything you have blood on your hands. I take my hat off to Pierre Kory FLCCC, Thomas Barody in Australia which advised Ivermectin combined with Doxycyline & Zinc is effective COVID treatment. Politicians, WHO & even people in the medical industry getting paid off hang your heads in shame!

  39. Paul Deane says:

    I have been following this for nearly a year. India is the first to bring legal action to this blocking of the use of Ivermectin in treatment. That’s treatment. Why the huge push for vaccines and not a similar effort to treat people with the disease. It is malpractice by the medical community. There will be more legal actions coming forward. I would not be surprised if criminal actions eventually come up toward The Who and big Pharma in their efforts to block the use of this drug along with other therapeutic drugs. Where is there any emergency use actions in the US for therapeutics?

    1. D.C. Stolk says:

      Paul, that´s because vaccins PREVENT people from becoming sick. Medication is for TREATMENT, if people are already sick. So you need both to fight Covid-19. And, so far, Ivermectine has NOT been proven to be a medication that helps against Covid.
      And yes, there is a lot of work being done on new medications that might work against Covid, as well as research being done on existing medications, to see if there are some that will also work against Covid. And they are doing RCTs on Ivermectine, to see if there is really a grain of truth in all the wild stories about IM.

      1. Susan Woodward says:

        Clearly, you have not read the studies showing ivermectin’s high efficacy in prophylaxis, nor Dr. Tes Lawrie’s meta-analysis of ivermectin studies, exemplary for its statistical rigor, protocol, and integrity. For an organization of such supposed academic stature, I find Lowe’s article lacking in evidence demonstrating balanced familiarity and evaluation of the literature, as well as honesty in pointing out study design and analyses deficits, rather like an overcooked noodle: a little slimy with no substance.

      2. theasdgamer says:

        Proven absolutely, no, ivermectin lacks this evidence. However, the bulk of the evidence favors using ivermectin and HCQ to treat covid

        EARLY

        …within three days of symptom onset

        (I had to shout in order to cater to the intellectually deaf readers.)

        On what day was there a minimum of false negative PCR results? Three days after symptom onset, which corresponds to max viral load, by inference.

        Proven absolutely, no. But there is sufficient evidence to proceed ad hoc with early antiviral treatment on suspicion.

        Maybe it will reduce premature deaths and long covid.

  40. James says:

    What, specifically, is wrong with the analysis in “Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19” published in the American Journal of Therapeutics?

    Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19

  41. Manuel says:

    This colombian study is totally flawed.
    Please check this out:
    https://c19ivermectin.com/lopezmedina.html

    And please have special look on the conflict of interest statement:
    Conflict of Interest Disclosures: Dr López-Medina reported receiving grants from Sanofi Pasteur, GlaxoSmithKline, and Janssen and personal fees from Sanofi Pasteur during the conduct of the study. Dr López reported receiving grants from Sanofi Pasteur, GlaxoSmithKline, and Janssen and personal fees from Sanofi Pasteur during the conduct of the study. Dr Oñate reported receiving grants from Janssen and personal fees from Merck Sharp & Dohme and Gilead outside the submitted work. Dr Torres reported receiving nonfinancial support from Tecnoquímicas unrelated to this project during the conduct of the study. No other disclosures were reported.

  42. Jon Hammerton says:

    Dear Sir,

    When writing articles that are critical in nature and go against the ‘doctrine’ of the pharmaceuticals, you should probably list your conflicts of interests:

    “’worked for several major pharmaceutical companies since 1989”

    You do no analysis of the mountain of compelling data. Virologists with much greater experience than you would like to debate you, I’m sure. I hope your soul is not so lost that you can’t see that Mexico has reduced Covid to almost nothing with Ivermectin alone.

    Hope you find peace with yourself and your money.

  43. Charles Geraghty says:

    What has been your preferred approach to treat covid infected patients in order to try and prevent hospitalisation?

  44. Sean M says:

    “Conspiracy theories” are not inherently more or less falsifiable than other theories. It is possible to endlessly add epicycles and move goalposts to defend any hypothesis, including “anti-conspiracy” theories (which assert that “mistakes were made”– just incompetence or error, not private coordination for antisocial ends).

    This is otherwise a good article, but seeing “conspiracy theory” deployed as a slur weakens the Lowe’s credibility.

  45. Jan Sunner says:

    As a casual observer of this very interestin case of “science in action” and with no expertize in the area, I do note that some of the discrepancies between ivermectin observations could possibly be explained if one does NOT assume that the drug’s (lack of) effect on disease progression for individuals necessarily paralells the effect on COVID transmission rates.

  46. SRP says:

    Fairly skeptical about Ivermectin myself; here’s another meta-analysis and claim of mechanism(s) to support anti-COVID effectiveness.
    https://www.nature.com/articles/s41429-021-00430-5?fbclid=IwAR2vkSOu3JjaaPnNFKL7p9wozxLRKKlu0kO6IZ9nauy9yAeAY4FEtB2BepY

  47. Gary says:

    Why haven’t there been larger studies? If the drug companies stood to profit on this treatment, don’t you think there would be?

  48. Kevin Teh says:

    The most convincing evidence for me has been the comparison of case counts in states that adopted Ivermectin for treatment versus those that did not in Peru, India and Mexico. There doesn’t seem to be anything else that could explain the dramatic drop in cases in regions that started treating with Ivermectin. I don’t understand how people could look at that data and not find it convincing.

    1. theasdgamer says:

      Well, if case counts drop after giving vaccines that make huge profits for pharma, those drops will be considered to have occurred due to the vaccines.

      In my county, deaths began dropping a month before vaccines were rolled out, but they must have had a time machine because their impact was felt before the rollout.

  49. Mr. Robert H says:

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  51. Luis Medina says:

    ¨A team in Colombia looked at 200 ivermectin-treated patients and 200 controls with mild coronavirus infections, and found no statistical differences between the two. Objections have been raised to that trial’s use of an oral suspension formulation, I should note.¨ If you read the article you can notice that both placebo and treatment actually received ivermectin!!!…. and yet another case of conflicts of interest! go down to the article and read the disclosed conflicts of interest.

  52. Big Fool says:

    Derek:

    Your comment (re-quoted below) on the conspiracy theorists was the best I’ve read on describing that bunch, their mindset and the utter foolishness of those people.

    Thanks for writing it.

    “And as for the further bunch that are ready to go the conspiracy-theory route, well, as you’d imagine, I’m not having it. As usual, letting that stuff into your head simplifies everything enormously. Things get way too simple, actually. Everything bad is Their Fault, and you’re on the side of the good guys, the angels, struggling against the dark evil forces. It’s a bit like the pre-modern habit of thinking that made someone, every time they come down with some illness or problem, immediately wonder what witch or evil spirit did this to them. Someone has to be to blame, because nothing “just happens”. For the advanced conspiracy theorist, there are no accidents and there are no coincidences: things either directly support the all-encompassing theory, or they just show how the conspiracy is even bigger than it first appeared. It’s non-falsifiable – you can like your favorite conspiracy framework or you can love it, and those are your only choices.”

  53. Chris says:

    What about the positive results of Ivermectin in India?

    https://www.thedesertreview.com/news/national/ivermectin-obliterates-97-percent-of-delhi-cases/article_6a3be6b2-c31f-11eb-836d-2722d2325a08.html

    Could it be that this cleared out the other things afflicting these poor people, so their bodies could more al take on COVID?

    1. Ravenous bugblatter says:

      These supposed positive results from India just happen to coincide with lockdowns and curfews. Why wouldn’t infections fall?

  54. Jose says:

    Here’s medical specialist who said he has successfully treated many covid patient with Ivermectin.
    https://odysee.com/@SaveMedia:5/capitol-clarity-ryan-cole-on-covid-19-vitamin-d-vaccine-concerns:2

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