Ivermectin is an antiparasitic drug that is well established for use in animals and people. The World Health Organization (WHO), the European Medicines Agency (EMA), the United States Food and Drug Administration (FDA), and the Infectious Diseases Society of America (IDSA) all advise against using ivermectin in an attempt to treat or prevent COVID-19.
Early in the COVID-19 pandemic, laboratory research suggested ivermectin might have a role in preventing or treating COVID-19. Online misinformation campaigns and advocacy boosted the drug's profile among the public. While scientists and physicians largely remained skeptical, some nations adopted ivermectin as part of their pandemic-control efforts. Some people, desperate to use ivermectin without a prescription, took veterinary preparations, which led to shortages of supplies of ivermectin for animal treatment. The FDA responded to this situation by saying "You are not a horse" in a Tweet to draw attention to the issue.
Subsequent research failed to confirm the utility of ivermectin for COVID-19, and in 2021 it emerged that many of the studies demonstrating benefit were faulty, misleading, or fraudulent. Nevertheless, misinformation about ivermectin continued to be propagated on social media and the drug remained a cause célèbre for anti-vaccinationists and conspiracy theorists.
Research
Some in vitro drug screening studies early in the pandemic showed that ivermectin has antiviral effects against several distinct positive-sense single-strand RNA viruses, including SARS-CoV-2. Subsequent studies found that ivermectin could inhibit replication of SARS-CoV-2 in monkey kidney cell culture with an IC50 of 2.2–2.8 μM.
However, doses much higher than the maximum approved or safely achievable for use in humans would be required for an antiviral effect while treating COVID-19. Aside from practical difficulties, such high doses are not covered by current human-use approvals of the drug and may be toxic, as the antiviral mechanism of action is believed to be via the suppression of a host cellular process, specifically the inhibition of nuclear transport by importin α/β1. Several other drugs which inhibit importin α/β1 at therapeutic doses have failed clinical trials due to systemic toxicity and a narrow therapeutic window.
To resolve uncertainties from previous small or poor-quality studies, , large scale trials were underway in the United States and the United Kingdom.
A large randomised controlled trial ACTIV-6, published in October 2022, found no significant difference between patients treated with ivermectin and placebo, and was described by Yale medical professor Perry Wilson as the "final nail in the coffin" for ivermectin as a treatment for covid.
Research limitations, ethics and fraud
Many studies on ivermectin for COVID‑19 have serious methodological limitations, resulting in very low evidence certainty. Several publications that supported the efficacy of ivermectin for COVID‑19 have been retracted due to errors, unverifiable data, and ethical concerns.
Several high-profile publications purporting to demonstrate reduced mortality in COVID-19 patients were later retracted due to suspected data falsification. This only added to confusion among the media and lay public, as these publications had been widely cited by ivermectin supporters and included in meta-analyses.
In January 2022, 22 inmates at the Washington County Detention Center in Arkansas filed a lawsuit over hundreds of ivermectin pills given to them as "vitamins" in 2020.
In February 2022, the American Journal of Therapeutics issued expressions of concern against two positive systematic reviews of ivermectin for COVID-19 which it had published in 2021, because of suspicions about the underlying data that would undermine these papers' findings of benefit.
In Mexico City the government distributed ivermectin widely as a COVID-19 treatment and published the observed results on the SocArXiv archive as a research paper. The paper was subsequently withdrawn by the archive citing concerns that it was unethical, as it effectively was an experiment carried out on people without gaining informed consent. Philip N. Cohen of the SocArXiv steering committee said "the article is of very poor quality or deliberately false and misleading" and that its removal was justified to prevent public harm.