Is this why ivermectin seems to work on COVID in some studies?

AP Photo/Mike Stewart

A fascinating piece from someone whose work many righty blog readers already know. It’s Scott Alexander, formerly of Slate Star Codex, now of Astral Codex Ten. Alexander is a psychiatrist by trade and thus well equipped to do a deep dive through the many studies showing some benefit from ivermectin in fighting COVID.

And when I say “deep,” I mean deep. He analyzes a few dozen studies, individually, before reaching his conclusion. If you intend to read the entire piece, set aside half an hour at least.

Alexander ends up discarding a majority of the studies due to flaws — poor methodology in some cases, outright fraudulent data in others. Some weren’t randomized clinical trials, in which subjects are split into two groups and one is given a placebo to form a benchmark of comparison with the group that got the drug. But even so, some studies did clear the bar of credibility and did show some efficacy from ivermectin.

Does it actually work on COVID after all?

One thing you’ll notice as you read through Alexander’s summaries of the studies is his attentiveness to where each was conducted. Lots of trials from Bangladesh, Pakistan, India, Egypt, and a few from South America (Argentina, Colombia). Poor countries were heavily represented. Which got him to thinking: Maybe ivermectin appears to work on COVID in those countries because it’s actually working to resolve a common comorbidity there. It’s an anti-parasitic drug, right? Well, Alexander got out his map of where parasites like roundworms are most prevalent globally, and lo and behold. The nations where the drug seemed to reduce the severity of COVID are hot spots for parasites.

Maybe ivermectin seems to “work” against COVID because it’s actually working to reduce parasites in the COVID patients who received it. Once their immune systems are no longer burdened by worms, they’re more capable of fighting off an infection naturally.

As several doctors and researchers have pointed out (h/t especially Avi Bitterman and David Boulware), the most impressive studies come from places that are teeming with worms. Mahmud from Bangladesh, Ravakirti from East India, Lopez-Medina from Colombia, etc.

Here’s the prevalence of roundworm infections by country (source). But alongside roundworms, there are threadworms, hookworms, blood flukes, liver flukes, nematodes, trematodes, all sorts of worms. Add them all up and somewhere between half and a quarter of people in the developing world have at least one parasitic worm in their body.

Being full of worms may impact your ability to fight coronavirus…

The most relevant species of worm here is the roundworm Strongyloides stercoralis. Among the commonest treatments for COVID-19 is corticosteroids, a type of immunosuppresant drug. The types of immune responses it suppresses do more harm than good in coronavirus, so turning them off limits collateral damage and makes patients better on net. But these are also the types of immune responses that control Strongyloides. If you turn them off even very briefly, the worms multiply out of control, you get what’s called “Strongyloides hyperinfection”, and pretty often you die.

So you need to “address the risk” of strongyloides infection during COVID treatment in roundworm-endemic areas.

Possibly the best-known fact about COVID is that people with underlying health problems are at greater risk of severe illness or death than healthy people are. (The ultimate “underlying health problem” is age, of course.) Imagine if you took a population of obese people, with a high rate of death from COVID, and put them on an all-liquid diet for three months. We’d all expect the COVID death rate within the group to be lower going forward after those three months were up than it was before. But that’s not because we’d assume an all-liquid diet is some magical folk remedy against the virus. It’s because we’d reason that losing weight will ease some stress on their bodies, allowing their immune systems to naturally respond more robustly when infected.

If Alexander’s right then Americans who lack the particular comorbidity that made COVID extra-deadly in the Third World — parasites in their system due to poor sanitation — won’t benefit from ivermectin. The drug isn’t stopping the virus from replicating, it’s simply eliminating a potential preexisting health problem that might otherwise suppress one’s immune system. It makes me wonder, in fact, if something similar was happening last year amid the hydroxychloroquine craze. Hydroxychloroquine is an anti-inflammatory drug; maybe Americans with inflammation problems took it out of fear of COVID, experienced reduced inflammation, and their immune system was better able to fight the virus off.

Alexander does have some sympathy for ivermectin true believers, recognizing that belief in alternative treatments for COVID comes from the same place anti-vaxxism does, which is distrust of an expert class that seems hostile to them and their culture. But his sympathy only goes so far: “[T]he things people were claiming – that ivermectin has a 100% success rate, that you don’t need to take the vaccine because you can just take ivermectin instead, etc – have been untenable not just since the big negative trials came out this summer, but even by the standards of the early positive trials… I think the conventional wisdom – that the most extreme ivermectin supporters were mostly gullible rubes who were bamboozled by pseudoscience – was basically accurate.”

Meanwhile, in news about drugs that really do seem to work against COVID:

Pfizer has applied to the Food and Drug Administration to authorize its antiviral pill to treat unvaccinated people with Covid-19 who are at high risk of becoming severely ill, the company said on Tuesday…

A spokesman for Pfizer, Kit Longley, said that for now, the company is seeking authorization for its pill to be given only to unvaccinated people, but the company might submit amendments to that provision later, depending on the data from clinical trials. The F.D.A. has final say on who will be eligible to receive the pill.

Merck, which applied for authorization for molnupiravir last month, said it would be up to the F.D.A. to decide whether to authorize its pill for use in vaccinated people in addition to unvaccinated people.

The White House anticipates spending $5 billion to purchase courses of treatment of Pfizer’s wonder drug and another $2.2 billion on Merck’s. I find it unimaginable, though, that the pills will end up being authorized exclusively for the unvaccinated. Granted, an unvaxxed person needs it more urgently than a vaxxed person of their age and health profile does, but how do we tell a vaccinated elderly person who’s struggling to fight off a breakthrough infection that they’re on their own because the available supply of the miracle pill is being hogged by younger people who chose not to get their shots?

And what would limiting therapeutics to the unvaccinated do to vaccine uptake among that group? The feds are still pushing holdouts to give in and finally get their shots. But if the unvaxxed know that Pfizer’s pill is being set aside for them exclusively, they have less reason to go out and take prophylactic measures against severe illness by getting the jab. My guess is that the FDA ends up approving the pill for everyone and then lets doctors and hospitals decide how to prioritize among recipients.