Evidence Against Ivermectin Efficacy For COVID-19

Ivermectin has been promoted by certain factions as a miracle drug (yes, those exact words were used) against COVID-19.

But like Hydroxychloroquine, which was equally promoted before Ivermectin, neither have any effect on COVID-19.

So what is the evidence for or against Ivermectin? This article lists whatever evidence at the time of this writing.

Prelude

Note that I have a pharmacy degree and was licensed decades ago, but after a few short months, I switched to the new fangled computer thing.

So like any non-specialist, I lookup relevant information from expert sources, and check whether it is backed by evidence, under rigorous controlled testing conditions, or not.

If there is no evidence provided, there is not weight to the claim.

Conspiracy Claims, As Always

The proponents of HCQ and Ivermectin are stuck in a conspiratorial narrative that:

• vaccines are not needed, too new, expensive, unproven, or dangerous, and ...
• there are cheap drugs that work, and ...
• there is a conspiracy that big pharma, backed by governments, do not want you to know the truth.

What Is Ivermectin

Ivermectin is a drug used against parasites, such as whipworm, river blindness, ...etc.

The dose is between 150 to 200 mcg/kg of body weight, given as a single dose. It may be repeated after 3 or more months.

Ivermectin: Claims For Efficacy Against COVID-19

The proponents of Ivermectin for COVID-19 propose a higher does for multi-day treatment (e.g. 400 mcg/kg for 3 days).

This video is from the early days of Ivermectin alleged claims. It contains the claims from a doctor who testified to the US Congress that it works. The debunker (a molecular biologists) uses proper "evidence based methodology" to debunk it.

Ivermectin Inhibits COVID-19 In Vitro

Initial tests in vitro showed that Ivermectin inhibits the SARS-CoV-2 virus. However, this is in vitro, meaning it is against a cell culture in a petri dish, not a full organism made of thousands of types of cells interacting, with a liver and kidney that breaks down the drug, an immune system that does a myriad of things, and so on.

Moreover, the dose that is used for in vitro studies, may be toxic when given to a full organism.

Ivermectin Ineffective In Clinical Trials

The next step after in vitro, is in vivo, meaning animal or human studies. Better yet, full clinical trials that are double blinded (meaning neither the patient, nor the doctor knows which patients get the drug and which get the placebo).

The claimed evidence that it works first came from a study at Benha University (a small university in Egypt). Sadly, it turned out that the data was entirely fabricated. Not just innocent errors or lack of rigour, but actual medical and scientific fraud. The paper was later retracted by the journal.

The proponents of Ivermectin are usually those with dubious claims in other areas of medicine, such as "COVID-19 vaccines will cause massive deaths" without any evidence, and other unscientific views.

Ineffective In Proper Clinical Trials

Subsequent proper studies show no evidence of any benefit:

For example, this is a paper showing no reduction in hospitalization. It is a draft submitted to the British Medical Journal June 2022, and perhaps published by now. The paper's conclusion is as follows:

... resulted in less than one day of shortening of symptoms and did not lower incidence of hospitalization or death among outpatients with COVID-19

Another study published in the New England Journal of Medicine in Aug 2022, and testing several cheap and available medicines concludes:

None of the three medications that were evaluated prevented the occurrence of hypoxemia, an emergency department visit, hospitalization, or death associated with Covid-19.

A Randomized Clinical Trial published in JAMA Effect of Higher-Dose Ivermectin for 6 Days vs Placebo on Time to Sustained Recovery in Outpatients With COVID-19 finds no evidence that ivermectin is of any benefit:

Question: Does ivermectin, with a maximum targeted dose of 600 μg/kg daily for 6 days, compared with placebo, shorten symptom duration among adult (≥30 years) outpatients with symptomatic mild to moderate COVID-19?

Findings: In this double-blind, randomized, placebo-controlled platform trial including 1206 US adults with COVID-19 during February 2022 to July 2022, the median time to sustained recovery was 11 days in the ivermectin group and 11 days in the placebo group. In this largely vaccinated (84%) population, the posterior probability that ivermectin reduced symptom duration by more than 1 day was less than 0.1%.

Meaning: These findings do not support the use of ivermectin among outpatients with COVID-19.

Meta-analysis Studies Are Problematic

Proponents of Ivermectin have cited some meta-analysis studies.

A meta-analysis,, also called a systematic review is a review of published papers on a certain topic, applying a known methodology to exclude irrelevant or biased results, analyzing the remaining results, then coming to conclusions on whether the results statistically support (or not support) a certain conclusion.

One of the main proponents of such meta-analyses is Dr. Pierre Kory. He is the same person that testified to the US Senate on Ivermectin alleged efficacy, and championing it, even after the evidence showed otherwise.

The original often cited meta-analysis was shown to be lacking credibility and even called a Fake and Deceptive ivermectin meta-analysis (ivmmeta) by Dr. Susan Oliver, who explains what a meta-analysis / systematic review should be.

Dr. Yan Yu also reviewed it from a methodology point of view, and pointed out the errors.

The Cochrane Collaboration confirm these conclusions as well: Ethics and integrity in reviewing research: lessons from ivermectin.

Of note, the Cochrane Collaboration is a global independent network of researchers, professionals, patients, carers and people interested in health. The members are 50,000 people from 130 countries, working on producing credible, accessible health evidence.

Ivermectin's Maker Says: Not Effective

And then we have the company that makes Ivermectin, who could have made a lot of money if that drug proved to be effective, saying that the evidence is against the claimed efficacy.

Company scientists continue to carefully examine the findings of all available and emerging studies of ivermectin for the treatment of COVID-19 for evidence of efficacy and safety. It is important to note that, to-date, our analysis has identified:

• 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.

We do not believe that the data available support the safety and efficacy of ivermectin beyond the doses and populations indicated in the regulatory agency-approved prescribing information.

Example Of Cheap Medicines For COVID-19

Oh, and we know that cheap medicines do work for COVID-19 in certain cases. And they are being used too ...

Pre-Omicron, the variants (Delta was the worst) attacked the lower respiratory tract (bronchus, alveoli) causing pneumonia. Thankfully, Omicron attacks the upper respiratory tract (nose, pharynx, larynx), so pneumonia is not an issue, though long COVID is still a significant risk.

Dexamethasone is an off-patent, cheap, generic drug that is prescribed when a COVID-19 patient transitions from the viral phase (first week) to the early inflammatory phase (2nd week), where it is the immune system that is causing the damage, not the virus itself. The sign to give dexamethasone is reduced blood oxygen which can be measured by an oximeter (the thing that clips on the finger). Dexamethasone reduces the inflammation and hopefully patients recover from pneumonia.

Ursodeoxycholic acid (UDCA)

Here is another example showing that researchers have the freedom to investigate off patent FDA approved drugs, and that medical journals do publish the results.

UDCA is a liver medicine that is widely used and off patent. Research in animals, and human organoids shows that UCDA reduces SARS-CoV-2 entry into cells. The research was done at MRC Cambridge Stem Cell Research Institute (a top research institution), and published in the journal Nature (a top science and medicine journal).

Of course, the time consuming and expensive part still remains: clinical studies, before it can be widely used.

Effective Against A Does Not Mean Also Against B

It is just like Hydroxychloroquine: what works against a certain pathogen or disease at a given dose, at does not work for other pathogens or conditions at a different dose. Viruses and intestinal worms have very different biologies and modes of infections (one is inside the cells, the other is outside, for one).

One example with dire consequences is thalidomide. It was used as a painkiller (like Tylenol), then its use was expanded for morning sickness for pregnant women. The result was babies were born with incomplete hands or feet. Canada, the UK and Europe allowed that use with disastrous results. In the USA, one Dr. Frances Oldham Kelsey who worked for the FDA refused to approve the drug, and stuck to her position that the company must submit safety data, despite pressure from superiors.

Oh, and she was Canadian too ...

What Happens When A Medicine Is Used Incorrectly

What happens when the same drug that saves lives in certain conditions, and doses, is administered at different does, or the wrong timing?

One word: Disaster!

In India, doctors were too aggressive and gave dexamethasone (or other corticosteroids) in the first week, suppressing the immune system, and there were lots of cases of mucormycosis (black fungus) which killed tissues around the nose and eye, permanently disfiguring some people.

We also see ill-effects in Ivermectin, because it was over-hyped without clear evidence. Some of those who are affected by conspiracy theories have taken it, or recommended it to friends and relatives.

What is the result? Toxicity ...

Doctors wrote letters to the New England Journal of Medicine showing that Toxic Effects from Ivermectin Use Associated with Prevention and Treatment of Covid-19, causing some patients to need hospitalization, while others needed Intensive Care!

What Works For COVID-19

So no, neither HCQ nor Ivermectin do any good for COVID-19 ...

And yes, vaccines are our best shot, followed by Paxlovid, and perhaps one or two monoclonal antibodies that did not have their efficacy reduced by viral mutations.

Note: for Paxlovid and the monoclonals, they do require proper timing, and must be given in the first few days, otherwise it will do no good at all. The same goes for Tamiflu against influenza.

Conclusion

Evidence based medicine, including double blinded studies, are our best methodologies so far that can help with finding new treatments and cures.

Chasing these miracle drugs is harmful. Not only because of direct harm from the drug itself, but wider and perhaps more serious and long lasting harms: a) discrediting the scientific process as the main avenue for exploring the world around us, including finding causes and remedies for the various diseases; and b) damaging societal cohesion by creating divisions in an area that traditionally has no seen such divisions. Such damage will spill over to other areas, such as education, politics, ...etc.

It would be nice if the vast majority can be convinced by evidence presented, not clinging onto falsified data or preconceived conspiracy theories. But obviously, this is no longer the world we live in, amplified by social media ...