Ivermectin may help covid-19 patients, but only those with worms

“THIS IS COMING,” crowed Andrew Hill, the lead author of an unreviewed meta-analysis looking at whether ivermectin, an anti-parasitic drug, was helpful for treating covid-19. “Get prepared, get supplies, get ready to approve it,” advised Dr Hill, a visiting fellow at the University of Liverpool.

Such advocacy proved far too optimistic. One of the papers cited in the report was withdrawn because its data were fraudulent; the report itself was retracted as well. Two of the largest and most rigorous randomised controlled trials also found no evidence the drug was helpful. As a result, ivermectin has never become part of the standard of care for covid-19.

Yet ivermectin’s advocates insist that there is solid science demonstrating the drug’s efficacy. One well-documented website lists and links to 65 different papers on the subject, many of which, on the surface, seem to support this claim. Could this many studies all be wrong? Recent analysis by Avi Bitterman, a dermatologist in New York, and Scott Alexander, a prominent blogger, suggests that the answer is nuanced. Ivermectin probably does help one subset of covid-19 patients: those who are also infected by the worms it was designed to fight.

Wading through the papers whose methodologies appeared sound, Dr Bitterman noticed that the studies that looked best for ivermectin tended to cluster in regions with high rates of infections by strongyloides, a parasitic worm. Common in much of Africa, Asia and Latin America, strongyloides can cause, among other things, diarrhoea, fatigue and weight loss. However, they only pose a graver threat if their numbers grow out of control. Such “hyper-infection”, which is often fatal, becomes far more likely if a patient is receiving corticosteroids, which both suppress the immune system and appear to make female worms more fertile. And dexamethasone, a corticosteroid, is now a standard treatment for severe covid-19, because it prevents the immune system from going into overdrive and attacking the body’s own cells.

Building on observations by David Boulware, a professor of medicine at the University of Minnesota, Dr Bitterman concluded that strongyloides may account for the conflicting results of studies about the effectiveness of ivermectin as a treatment for covid-19. In trials conducted in countries where the parasites are common, many people could have both covid-19 and strongyloides infections. Covid-19 might already have weakened their bodies’ defences against the worms; treating the coronavirus with corticosteroids would let the parasites run wild.

In the groups who received ivermectin during trials, the drug would keep strongyloides in check. But patients in control groups would be left at the worms’ mercy. This would make it look as if ivermectin were preventing deaths caused solely by covid-19, when in fact it was preventing those caused by the parasites or by a combination of the two infections. This mechanism would explain why most studies conducted in places where strongyloides are rare showed no benefit from taking ivermectin. “Ivermectin doesn’t treat covid,” Dr Bitterman wrote. “It treats parasites (shocker) that kill people when they get steroids that treat covid.” He concluded that “taking strongyloides endemic populations, putting them into a control group with corticosteroids is a death sentence”.

In July 2020 a group of doctors argued in the Journal of the American Medical Association that it was “reasonable to consider presumptive treatment with ivermectin for moderate- to high-risk patients not previously tested or treated for strongyloides”, and said that the risk of infection by the worms in covid-19 patients should be “based on factors such as country of origin and long-term residence”. The World Health Organisation also recommends ivermectin in this context. However, most people in rich Western countries like America—where demand for ivermectin, driven by advocates on social media, is so high that some people have resorted to taking the equine version of the drug—do not fit this description. At least when treating patients who have never been to countries with widespread strongyloides, the evidence suggests that mainstream doctors in such places are right to avoid prescribing ivermectin. ■

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