Misleading: The fact that ivermectin is safe and effective against parasitic infections doesn’t indicate that it will also be safe and effective for COVID-19. To do that, ivermectin would need to demonstrate its safety and efficacy in COVID-19 patients specifically.
AFFIRMATION COMPLETE: “Despite the spectacular worldwide effect profile, of excellent effect against COVID-19, with 0.26% observed minor side effects, and its use across several continents, ivermectin is widely shunned and ignored”
REVIEW
On 25 December 2022, the Epoch Times reposted an article by naturopath Colleen Huber titled “Ivermectin is Safe and Effective: The Evidence”. At the time of this review’s publication, the article had received more than 4,500 interactions and 1,700 shares on Facebook, according to social media analytics tool CrowdTangle.
First published on Substack on 9 September 2021, the article accused public health authorities and media of ignoring the evidence supporting ivermectin’s safety and effectiveness as a COVID-19 treatment. But this claim is unsupported and misleading. While it is true that ivermectin is safe and effective against a wide range of parasitic infections in humans and animals, the same hasn’t been established for ivermectin as a COVID-19 treatment so far.
Due to the lack of supporting evidence, public health authorities like the World Health Organization (WHO) and the U.S. National Institutes of Health, and regulatory bodies like the U.S. Food and Drug Administration and the European Medicines Agency don’t recommend using ivermectin to treat or prevent COVID-19 except in clinical trials designed for testing these effects.
Huber had previously promoted unproven cancer cures and spread COVID-19 misinformation, as documented in multiple fact-checks and in this article by oncologist David Gorski on the blog Respectful Insolence.
Ivermectin demonstrated its safety and effectiveness against parasitic infections, not as an antiviral in COVID-19 patients
Huber’s article presented ivermectin as a “tremendously effective, safe, and low-cost” medicine included in the WHO’s 2019 Model List of Essential Medicines for its safety and efficacy. While factually accurate, Huber’s narrative misleads the reader into believing that this status also applies to COVID-19 when it doesn’t.
Ivermectin is a derivative of avermectin, a naturally-occurring compound discovered by William Campbell and Satoshi Omura in the late 70s. Ivermectin has been safely used as an antiparasitic for over three decades, winning Campbell and Omura the Nobel Prize for Physiology or Medicine in 2015.
But the fact that ivermectin is safe and effective against one infectious agent, such as a parasite, isn’t evidence that it has the same effects against another infectious agent, such as the virus SARS-CoV-2. Existing drugs used for one disease still need to undergo clinical trials to demonstrate that they are safe and effective in patients with another disease.
Experiments in cells cultured in the laboratory showed that ivermectin has antiviral activity, including against SARS-CoV-2[1-5]. However, the effects of a drug on a group of cells growing in a Petri dish don’t necessarily reflect what happens in the human body, which is far more complex. In people, ivermectin has only shown it is safe and effective in the conditions used against parasitic infections, not against COVID-19.
The evidence cited in Huber’s article is flawed and doesn’t support the use of ivermectin in COVID-19 patients
One of the main pieces of evidence presented in the article is a “meta-analysis of 63 studies of ivermectin versus COVID-19 in humans”. A meta-analysis is a type of review that combines data from several studies to gain statistical power. Based on the results of this analysis, Huber claimed that patients treated with ivermectin showed an “improvement” of 69% when using the drug early and that ivermectin reduced COVID-19 mortality by 76% compared to the control group. It also claimed that using ivermectin before exposure, for preventing infection, led to an improvement of 86%.
The article didn’t include any reference to the cited analysis. However, based on Huber’s description, the data source might be an analysis posted on the website c19ivm.org. Although the analysis results are frequently updated, an archived version from 7 September 2021 including 63 studies shows language and figures very similar to those reported in Huber’s article two days later.
The website claimed to present a “living analysis” of ivermectin as a COVID-19 treatment, concluding that “Ivermectin is an effective treatment for COVID-19”, particularly when used early. However, several issues call into question the validity of the results and conclusion.
One critical issue is the quality of the studies. According to the website, the analysis included clinical studies evaluating the effect of ivermectin in COVID-19 patients compared to a control group. Only 44 of them were peer-reviewed, while the remaining 19 were preprints—manuscripts that haven’t yet been reviewed by other scientists. The authors retrieved these papers from scientific literature databases, preprint servers, clinical trial registries, and spontaneous submissions to the site.
A closer look into these references readily shows that at least six of them, including three peer-reviewed studies, were later retracted for containing unsupported claims or due to methodological or ethical issues. At least one more has a published expression of concern. The inclusion of such articles raises concerns about the quality of the other data included in the analysis, which can greatly influence the conclusions of the meta-analysis and make them unreliable.
A September 2021 article on the website Ars Technica pointed out many other methodological issues in the meta-analysis, including aggregating data from studies with completely different designs, populations, outcome measures, and ivermectin dosage. Many studies also coadministered other drugs together with ivermectin. As the article on Ars Technica explained, such heterogeneous data in an analysis that also didn’t account for potential biases are unlikely to provide reliable results.
Another red flag is that, along with ivermectin, the c19ivm website promoted several other unproven compounds as effective COVID-19 treatments, such as hydroxychloroquine, zinc, and vitamins. Finally, the c19ivm website doesn’t disclose the author’s identities, affiliations, or potential conflicts of interest. Instead, it simply states « We are PhD researchers, scientists, people who hope to make a contribution”, making it impossible to verify the authors’ experience in conducting such analyses.
Large-scale clinical trials didn’t identify benefits from ivermectin treatment in COVID-19 patients
Some early preclinical studies suggested that ivermectin might benefit COVID-19 patients[5,6]. These results prompted researchers worldwide to launch clinical trials evaluating ivermectin’s effectiveness against COVID-19. At a time when COVID-19 vaccines weren’t yet available, ivermectin became increasingly popular among some doctors and patients as a “miracle drug”, despite the lack of evidence supporting its use against COVID-19.
In October 2021, the BBC reported that “more than a third of 26 major trials of the drug for use on Covid have serious errors or signs of potential fraud. None of the rest show convincing evidence of ivermectin’s effectiveness”. Retraction Watch, a blog that reports on retractions of scientific studies, posted a Twitter thread listing all retracted studies on ivermectin up to July 2022.
And as Health Feedback explained in several earlier reviews, randomized, controlled clinical trials haven’t shown that ivermectin treatment benefits COVID-19 patients[7-10]. A July 2021 Cochrane Systematic Review concluded that most of the evidence available then was of low quality and didn’t support “the use of ivermectin for treatment or prevention of COVID-19 outside of well-designed randomized trials”. In a June 2022 update, the review concluded there was “no evidence to support the use of ivermectin for treating COVID-19 or preventing SARS-CoV-2 infection”[11]:
“For outpatients, there is currently low- to high-certainty evidence that ivermectin has no beneficial effect for people with COVID-19. Based on the very low-certainty evidence for inpatients, we are still uncertain whether ivermectin prevents death or clinical worsening or increases serious adverse events, while there is low-certainty evidence that it has no beneficial effect regarding clinical improvement, viral clearance and adverse events”
Conclusion
The article reposted in the Epoch Times claiming to provide evidence that ivermectin is a safe and effective COVID-19 treatment is unsupported and misleading. Part of this supposed evidence is based on ivermectin’s safety and efficacy against parasitic infections, not COVID-19. Another part is a meta-analysis of obscure origin, whose conclusions are unreliable owing to its methodological flaws. These data are insufficient to overturn the evidence from several large clinical trials in humans which haven’t identified benefits from ivermectin treatment in COVID-19 patients.
REFERENCES
- 1 – Götz et al. (2016). Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import. Scientific Reports.
- 2 – Lundberg et al. (2013) Nuclear import and export inhibitors alter capsid protein distribution in mammalian cells and reduce Venezuelan Equine Encephalitis Virus replication. Antiviral Research.
- 3 – Tay et al. (2013) Nuclear localization of dengue virus (DENV) 1–4 non-structural protein 5; protection against all 4 DENV serotypes by the inhibitor Ivermectin. Antiviral Research.
- 4 – Wagstaff et al. (2012) Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import able to inhibit replication of HIV-1 and dengue virus. Biochemical Journal.
- 5 – Caly et al. (2020) The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Research.
- 6 – Dias de Melo et al. (2020) Anti-COVID-19 efficacy of ivermectin in the golden hamster. EMBO Molecular Medicine.
- 7 – Reis et al. (2022) Effect of Early Treatment with Ivermectin among Patients with Covid-19. New England Journal of Medicine.
- 8 – Lim et al. (2022) Efficacy of Ivermectin Treatment on Disease Progression Among Adults With Mild to Moderate COVID-19 and Comorbidities: The I-TECH Randomized Clinical Trial. JAMA Internal Medicine.
- 9 – Bramante et al. (2022) Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19. New England Journal of Medicine.
- 10 – Naggie et al. (2022) Effect of Ivermectin vs Placebo on Time to Sustained Recovery in Outpatients With Mild to Moderate COVID-19: A Randomized Clinical Trial. JAMA.
- 11 – Popp et al. (2022) Ivermectin for preventing and treating COVID-19. Cochrane Database of Systematic Reviews.
