Does the anti-parasitic Ivermectin work in actual human studies versus the Petri dish in vitro studies, when treating coronavirus COVID-19 infection? And if so, is it safe in humans?

An in vitro study was done.


What's true has changed a lot since this question was asked and initially answered.

Does CHEST only publish results of INvalid clinical evidence? No. It's v. reputable. Yes, this retrospective study shows it works, and likely works much better than the other treatments already in use.

Title, Link: Use of Ivermectin Is Associated With Lower Mortality in Hospitalized Patients With Coronavirus Disease 2019

And in addition to reliable clinical evidence (which Cochrane says evidence shows is as reliable as RCT evidence) there are a great many preprint results from RCT and published results from RCT. Rather than put up a static, soon to be wrong summary, I point to this:

The FLCCC's comprehensive review of the emerging evidence for Ivermectin use in our I-MASK+ protocol (PDF, continuously updated) (It currently has 87 citations and resolves to this URL but that is sure to change.)

They put it thus in their review:

To our knowledge, the current review is the earliest to compile sufficient clinical data to demonstrate a strong signal of therapeutic efficacy based on numerous clinical trials in multiple disease phases, however it is limited by the fact that only a minority of studies have been published in peer-reviewed publications, with the majority of results compiled from manuscripts uploaded to medicine pre-print servers or from registered trials that have posted preliminary results on clinicaltrials.gov.

But "minority" != 0. Overall, the results are largely highly significant. Results from 16 clinical trials and 3 large case series are reviewed.

They even mention:

Two manuscripts reviewing the scientific rationale and evolving published clinical evidence base in support of the MATH+ protocol passed peer review and have been accepted for publication in major medical journals at two different time points in the pandemic (2, 3).

People have already received far over three billion < sic > doses, and the record of significant adverse reports indicates is about as safe as medicine gets.

(The ~Sphere data-derived paper is obviously garbage and merits scant not attention outside the tabloids.)

Another retrospective study is based on over 1 million doses distributed in one of each of several paired Brazilian cities. Another compares regions in Paraguay that did and didn't receive ivermectin. Another compares African states where ivermectin is and isn't distributed nationwide. In each study, cases and deaths, tracked over time, diverge, strongly according to ivermectin distribution.

  • Also note: the FLCCC had no interest in ivermectin when it formed. It did quickly recognize and promote the benefits of steroids in severe cases, but the medical establishment took several months to recognize that, and they note: "Despite the plethora of supportive evidence, the MATH+ protocol for hospitalized patients has not yet become widespread." It was months later that they began to champion ivermectin as well. – Matthew Elvey Dec 4 '20 at 7:24
  • PS Please, if you've raised any objection, check to see if they've already been addressed by the FLCCC! – Matthew Elvey Dec 4 '20 at 8:08
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    @ Matthew Elvey I am ashamed to have given the wrong answer. The fatal part has been removed by a correction line. Let me make an excuse. It is not that I was without evidence; at the time, news of ivermectin's efficacy had not been introduced in ivermectin's "Birthplace";this site always introduced important news about ivermectin, but written in Japanese) I look now and see that the review you referred me to has been translated and presented in Japanese. – Blue Various Dec 4 '20 at 16:17
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    In the second report you presented, the data from Peruvian states and Alto Parana are very impressive. The improvement in prognosis of death and the timing of ivermectin administration are perfectly aligned. And without ivermectin, it wouldn't have happened. This is what clinical research should be about. On the other hand, the Utah paper, if it were real data, would have been a groundbreaking use of real-world data. – Blue Various Dec 4 '20 at 18:09
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    Agree! - "The improvement in prognosis of death and the timing of ivermectin administration are perfectly aligned." It's uncanny. Don't be ashamed! You're helping now! – Matthew Elvey Dec 4 '20 at 21:34

This in-vitro study reveals exciting data regarding Ivermectin, which is typically used for treatment of scabies.

I was unable to find any clinical data to support use of Ivermectin for COVID-19. But this study definitely supports starting a clinical trial given the widespread availability of Ivermectin. Overall ivermectin is well-tolerated in both children and adults, with rash being one of the most common side effects. It may have fewer severe adverse effects than hydroxychloroquine, which can cause fatal arrhythmias like Torsades de Pointes(though this is more with chronic use; https://www.ncbi.nlm.nih.gov/pubmed/16615675). This supports ivermectin as a good candidate drug to study.

It is important to note, however, that many drugs that have shown to be effective in-vitro will fail to produce any clinical benefit when given to animals or humans. For instance, for ebola virus, chloroquine was effective in-vitro but not in guinea pigs (https://www.ncbi.nlm.nih.gov/pubmed/26459826). There are many factors that could contribute to these discrepancies, including issues with bioavailability, distribution to the appropriate tissues, entrance into cells, and breakdown of the drug by cellular or viral mechanisms.


There is a paper which suggest that ivermectin is unlikely to be an effective antiviral vs. SARS-CoV-2 at recommended dosing.

Please find this preprint or this paper.

This paper has the following description.

Recently, an article by Caly et al. reported that ivermectin inhibited severe acute respiratory syndrome‐coronavirus (SARS‐CoV‐2) in vitro causing an ~ 5,000‐fold reduction in viral RNA at 48 hours with ivermectin at 5 μM. The concentration resulting in 50% inhibition (IC50) of 2 μM (1,750 ng/mL) is > 35× higher than the maximum plasma concentration (Cmax) of 0.05 µM (46.6 ng/mL)2 after oral administration of the approved dose (~ 200 μg/kg) and ivermectin showed little to no activity 1 μM in vitro. Because ivermectin is highly bound to serum albumin (93%), the IC50 is orders of magnitude higher than the unbound plasma Cmax after approved doses of ivermectin (0.0035 µM; 3.26 ng/mL).

Therefore, a large estimate is that the plasma concentration is 2 μM /0.0035 µM =571 times insufficient.

I think the key points of above paper are as follows;

  • The development of methods to realize enough concentrations of ivermectin in the lungs/plasma.
  • Is ivermectin still safe when the enough concentration is achieved in the lungs/plasma?

These questions follow naturally from the preprint/paper above.

However, as described in the @Matthew Elvey 's answer, as of December 5, 2020, there are many clinical results which suggest that we can get enough efficiency with far less dosage than would be assumed from pharmacokinetic considerations; formulas that combine several things such as zinc and vitamins seem to be more desirable.(Added on December 5, 2020)

The gap between inadequate blood levels and a strong clinical effect is one puzzle. It is an exciting scientific topic. This gap will be bridged as the mechanism of action of ivermectin is elucidated.

So far, various mechanisms have been proposed, but it has not been decided which one is the mainstay. That's what Satoshi Omura said in his open youtube lecture (In Japanese, the relevant part has been headed out.) at Showa Pharmaceutical University at the end of October, 2020.

The following is a summary of the youtube lecture by Satoshi Omura.

  • There are various proposed mechanisms of action by which ivermectin inhibits coronaviruses, and it is not clear which theory is definitively correct. He introduced the following two mechanisms as examples.
  • One is that ivermectin inhibits the process by which the viral spike joins ACE2 and enters the cell. This is an example of the idea of inhibiting viral entry. (Figure 1, left)
  • Dr. Maruta and colleagues in Australia have proposed a different mechanism. In that theory ivermectin acts on the human body. Briefly, when the virus binds to receptors such as ACE2, a kinase called PAK1 is induced. This is a release kinase, which appears to be released when infection occurs and suppresses the immune system. Their idea seems to be that ivermectin also protects the immune system by inhibiting PAK1. (Figure 1, right)

enter image description here
Fig.1 Examples of proposed mechanisms of action. Adapted from a lecture given by Satoshi Omura at the end of October 2020, partially written in Japanese.

In September 2020, Japan's Kitasato University appears to have begun a physician-led clinical trial for COVID-19. Kitasato University is where Satoshi Omura, one of the discoverers of ivermectin, is affiliated.

  • jRCT2031200120:A placebo-controlled, randomized, double-blind study in Covid-19 patients with ivermectin; An investigator initiated trial

They will administer the Ivermectin Tablets, sold under the brand name STROMECTOL, orally. According to a Japanese newspaper article (written in Japanese), the trial is expected to be completed in March 2021. (Completion = LPI?)

On the other hand, scandalous clinical data also exists. It seems that one data analysis company, Surgisphere published a preprint saying that ivermectin was beneficial based on analysis of real world data, but it was later retracted. According to this article, it seems to have pointed out many unnatural aspects of the data.

By the way, Ivermectin's 'birthplace' features hot news about Ivermectin. Note that a bit slow in terms of information; as of 5 December 2020, the introduction of the paper published on 10 November is the most recent. Even more unfortunate is that the information is in Japanese. However, it will be helpful to see the trends. For many people, though, they may need the help of machine translation.
https://kitasato-infection-control.info/ (Written in Japanese)

  • @ Matthew Elvey  The evidence you have shown me certainly looks promising. An oversight on my part. I'll correct my answer. Satoshi Omura is my senior at Tokyo University of Science; he is much older than me, though. In that sense, I am delighted with the paper you introduced to me. – Blue Various Dec 4 '20 at 15:12
  • Cool. So nice to see the warm reception here on SE to this info. (Seeing my answer has taken first place in < 24 hrs. First time I've seen anything like that even when my answer was irrefutable.) – Matthew Elvey Dec 4 '20 at 19:09
  • Do you still "think that the ivermectin is unlikely to be an effective antiviral vs. SARS-CoV-2 at recommended dosing?" It kind of depends on what dosing is recommended too. In the Covid trials so far, the dosing has been low, and effective. But in safety studies, 10x higher doses were found to be safe in humans, or at least to have minimal side effects - small n so hard to say. But with (correction: >3) billion standard doses, the adverse reports indicates is about as safe as medicine gets. – Matthew Elvey Dec 4 '20 at 19:16
  • I've further revised my answer. I think it's a mystery of sorts that the dose should be much less than 5000 times less. But this drug probably inhibits the impotin, not directly 'killing' the virus. So maybe the idea of DI itself doesn't fit. – Blue Various Dec 5 '20 at 2:55
  • I looked at the original paper and the dosing concentration, as I recall, wasn't anything like 5000x less. I should double check. Also, I recall reading that ivermectin concentrates in lung tissue and stays there for weeks. Impotin? You mean reproduction? – Matthew Elvey Dec 10 '20 at 23:08

(What's true has changed even further!! A lot changed AGAIN - since this question was asked and initially answered, AND THEN since it was (last month) initially answered by me! So time for another new answer!)

YES! In addition to several literature reviews by several groups of doctors including some of the most experienced in emergency medicine, and confirmed by their clinical experience as well as large population studies and medical groups in several countries on the latest research, there are two recent WHO-originated and funded endorsements of ivermectin. First, on the WHO website, ivermectin is recommended for treatment of Covid-19 patients when they are being treated with immunosuppressants. Secondly The WHO funded an evaluation of the evidence to date and the expert consultant the WHO relies on for such evaluations of evidence to be used as the basis for official WHO recommendations has spoken very encouragingly regarding the evidence from randomized controlled trials demonstrating the utility of Ivermectin in treating Covid-19 that his work so far has uncovered.

Andrew Hill for WHO: https://m.youtube.com/watch?v=yOAh7GtvcOs



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