When COVID-19 began to move around the world in early 2020, doctors faced a virus nobody understood, with no known treatments. In that vacuum, two old, cheap, well-known drugs; hydroxychloroquine and ivermectin, became the focus of enormous hope, and later, enormous controversy. This paper discusses why they seemed promising, how that promise fell apart under scrutiny, and what harm followed.

Neither drug was plucked from nowhere. Both offered plausible scientific reasons to be hopeful.

Hydroxychloroquine had been used safely for decades to treat malaria, lupus and rheumatoid arthritis. In laboratory cell cultures, it showed real antiviral activity against SARS-CoV-2, apparently by altering the acidity inside cell compartments in a way that blocked the virus from entering. It also has anti-inflammatory properties, and researchers wondered whether it might dampen the dangerous cytokine storms seen in severe COVID-19. Early in 2020, a small, poorly controlled French study reported rapid viral clearance in patients given hydroxychloroquine with the antibiotic azithromycin. That single unreliable study was amplified enormously by media, social platforms and political figures, and prescribing took off well before proper trials had been completed.

Hydroxychloroquine and ivermectin are not effective treatments for COVID-19

Ivermectin’s story is similar. It is a decades-old, safe and effective anti-parasitic drug, used worldwide against worm infections, scabies and river blindness. In 2020, an Australian laboratory study found that exposing cultured cells to ivermectin produced an approximately 5,000-fold reduction in viral replication. The proposed mechanism involved blocking the transport of viral proteins into the cell nucleus. News of that result travelled fast, and combined with a handful of small, non-randomised clinical reports suggesting benefit, ivermectin was very soon being heavily promoted on social media.

In both cases, the appeal was understandable: these were cheap, familiar, widely available drugs with a plausible biological story and a handful of encouraging early reports. But that combination; a lab result and a small uncontrolled study, have misled medicine and public perception before, and it did so again here.

The problem with laboratory antiviral activity is that it doesn’t tell you what happens in an actual human body. The ivermectin concentration that produced that dramatic result in cell culture was far higher than what standard, safe dosing could ever achieve in the human body. And COVID-19 entry via the human respiratory tract relies on a different viral entry pathway to the one used in the lab cell lines, one that hydroxychloroquine’s mechanism simply doesn’t touch. Elegant and careful test-tube experiments did not translate into clinical benefit.

The real test came from large randomised controlled trials, which, unlike the early observational reports, assign treatment by chance and so aren’t distorted by differences in age, illness severity or timing between patients who happened to get the drug and those who didn’t.

For hydroxychloroquine, the verdict arrived by mid-2020. The UK’s large RECOVERY trial found no difference in 28-day mortality between hydroxychloroquine and standard care, but noted longer hospital stays and a greater chance of needing ventilation in the group treated with hydroxychloroquine. The WHO’s international Solidarity trial found much the same. Both organisations halted their hydroxychloroquine arms, and the US FDA revoked its emergency authorisation. A later meta-analysis of 26 randomised trials covering over 10,000 patients found a small but statistically significant increase in mortality associated with hydroxychloroquine. In other words, treatment with hydroxychloroquine resulted in more deaths, not fewer.

For ivermectin, the picture that emerged was different but just as clear. Several of the early apparently positive studies turned out to have serious data problems, including implausible results and suspected duplication, and even outright faking of data. The strongest benefits came from the most poorly designed trials. When properly conducted, adequately powered trials were run, including the TOGETHER trial and the PRINCIPLE trial, they found no meaningful reduction in hospitalisation, recovery time or death. A comprehensive Cochrane review, the gold standard for evidence synthesis, concluded there was no reliable evidence that ivermectin prevents or treats COVID-19. https://www.cochrane.org/…/CD015017_ivermectin…

Misinformation about proper treatment can cause real harm.

For hydroxychloroquine, the evidence points to genuine harm at doses given to treat COVID-19. It can prolong the heart’s QT interval, raising the risk of dangerous arrhythmias, especially when combined with azithromycin. Trials also recorded higher rates of gastrointestinal upset, low blood sugar and liver problems, and a higher rate of death than for patients treated with recognised anti-viral medication. Beyond individual harm, the surge in off-label prescribing caused real shortages of hydroxychloroquine in malaria-prone areas, and for the lupus and rheumatoid arthritis patients who actually depend on it.

Ivermectin, taken at approved human doses, doesn’t show the same consistent signal of increased mortality. But that doesn’t mean using it against COVID-19 is harmless. Claims on social media led people to take veterinary formulations meant for livestock, in doses far beyond anything tested in humans. Poison control centres recorded a sharp rise in ivermectin toxicity cases, some resulting in serious neurological and respiratory harm, coma, and death. There is no antidote for ivermectin overdose.

There’s a broader harm too, shared by both drugs: opportunity cost. Time and money spent on medicines that don’t work is time not spent on care that does, including antivirals like nirmatrelvir–ritonavir and remdesivir given early to high-risk patients, and supportive care, oxygen and, in severe hospitalised cases, corticosteroids for those who need them. Chasing an ineffective treatment can delay effective ones, and that delay can carry major risks.

None of this means the initial interest in these drugs was irrational or dishonest. Scientists chase plausible leads; that’s how research works. Both drugs deserved a proper look. The real story isn’t that hydroxychloroquine and ivermectin were fraudulent claims. They were tested rigorously, as they should have been, and the rigorous evidence didn’t support them. Hydroxychloroquine appears to carry modest but real risks with no benefit; ivermectin appears to carry little direct risk at proper doses but no meaningful benefit either, alongside a real toxicity danger from misuse.

Following the evidence, rather than the social media posts, is what protects patients.