[caption id="attachment_330783" align="alignnone" width="720"] Ball-and-stick model of a hydroxychloroquine molecule[/caption]

In the early days of the Coronavirus epidemic, there were hopes that the disease could be treated with a compound called hydroxychloroquine (HCQ). HCQ is a long-established inexpensive medicine that is widely used to treat malaria. It also has uses for treating rheumatoid arthritis and lupus. There had been some indications that HCQ could treat SARS virus infections by attacking the spike proteins that coronaviruses use to latch onto cells and inject their genetic material. Initial small-scale studies of the drug on COVID-19 patients indicated some positive effect (in combination with the antibiotic azithromycin). President Trump, in March, promoted HCQ as a game-changer and is apparently taking it as a prophylaxis after potentially being exposed by White House staff.

Initial claims of the efficacy of this therapy were a perfect illustration of why we base decisions on scientific studies and not anecdotes. By late March, Twitter was filled with stories of "my cousin's mother's former roommate was on death's door and took this therapy and miraculously recovered". But such stories, even assuming they are true, mean nothing. With COVID-19, we know that seriously ill people reach an inflection point where they either recover or die. If they died while taking the HCQ regimen, we don't hear from them because...they died. And if they recover without taking it, we don't hear from them because...they didn't take it. Our simian brains have evolved to think that correlation is causation. But it isn't. If I sacrificed a goat in every COVID-19 patient's room, some of them would recover just by chance. That doesn't mean we should start a massive holocaust of caprines.

However, even putting aside anecdotes, there were good reasons to believe the HCQ regimen might work. And given the seriousness of this disease and the desperation of those trying to save lives, it's understandable that doctors began using it for critically ill patients and scientists began researching its efficacy.

Why Trump became fixated on it is equally understandable. Trump has been looking for a quick fix to this crisis since Day One. Denial failed. Closing off (some) travel to China failed. A vaccine is months if not years away. So HCQ offered him what he wanted -- a way to fix this problem without the hard work, tough choices and sacrifice of stay-at-home orders, masks, isolation and quarantine. So eager were they to adopt the quick fix, the Administration made plans to distribute millions of doses of this unproven drug in lieu of taking more concrete steps to address the crisis.[efn_note]Although the claim that Trump stands to profit off HCQ sales does not appear to hold much water.[/efn_note]

This is also why certain fringe corners of the internet became fixated on it. There has arisen a subset of the COVID Truthers that I'm calling HCQ Truthers: people who believe that HCQ isn't just something that may save some lives but is, in fact, a miracle cure that it's only being held back so that...well, take your pick. So that Democrats can wreck the economy. So that Bill Gates can inject us with tracking devices. So that we can clear off the Social Security rolls. And this isn't just a US phenomenon nor is it all about Trump. Overseas friends tell me that COVID trutherism in general and HCQ trutherism in particular have arisen all over the Western World.

It's no accident that the HCQ Truthers seem to share a great deal of headspace with the anti-Vaxxers. It fills the same needs

• In both cases, the idea was started by flawed studies. The initial studies out of China and France that indicated HCQ worked were heavily criticized for methodological errors (although note that neither claimed it was a miracle cure). Since then, larger studies have shown no effect.
• HCQ trutherism offers an explanation for tragedy beyond the random cruelty of nature. Just as anti-vaxxers don't want to believe that sometimes autism just happens, HCQ Truthers don't want to believe that sometimes nature just releases awful epidemics on us. It's more comforting, in some ways, to think that bad happenings are all part of a plan by shadowy forces.
• HCQ Trutherism offers convenient villians: the media, Democrats, scientists, "industry", Bill Gates, etc.

There is, however, another crazy side that doesn't get as much attention because their crazy is a bit more subtle. These are the people who have decided that, since Trump is touting the HCQ treatment, it must not work. It can not work. It can not be allowed to work. There is an undisguised glee when studies show that HCQ does not work and a willingness to blame HCQ shortages on Trump and only Trump.[efn_note]Not to mention the odd fish tank cleaner poisoning that has nothing to do with him.[/efn_note]

In between the two camps are everyone else: scientists, doctors and ordinary folk who just want to know whether this thing works or not, politics and conspiracy theories be damned. Well, last week, we got a big indication that it does not. A massive study out of the Lancet concluded that the HCQ regimen has no measurable positive effect. In fact, death rates were higher for those who took the regimen, likely due to heart arrhythmias induced by the drug.

So is the debate over? Can we move on from HCQ? Not quite.

First of all, the study is a retrospective study, looking backward at nearly 100,000 cases over the last four months. That's a massive sample that allows one to correct for potential confounding factors. But it's not a double-blind trial, so there may be certain biases that can not be avoided. In response to the publication, a group doing a controlled study unblinded some of their data (that is, they let an independent group look up who was getting the actual HCQ and who was getting a placebo). It did not show enough of a safety concern to warrant ending the study.

It's also worth noting that because this is an unproven therapy, it is usually being used on only the sickest patients (the odd President of the United States aside). It's possible earlier use of the drug, when the body is not already at war with itself, could help.

With those caveats in mind, however, this study at least makes it clear that HCQ is not the miracle cure some fringe corners of the internet are pretending it is. And it should make doctors hesitant in giving to people who already have heart issues.

As you can imagine, this has only fed the twin camps of derangement. The truther arguments tend to fall into the usual holes that truther theories do:

• "How can this be a four-month study when we only learned about COVID in January!" The HCQ protocol started being used almost immediately because of previous research on coronaviruses.
• "How come all of the sudden this safe medicine that people use all the time is dangerous?!" The side effects of HCQ have been well known for years and have always required consideration and management. They may be showing up more strongly here because it is being given to patients whose bodies are already under extreme stress. Also, azithromycin may amplify some of those side effects.
• "They just hate Trump." Not everything is about Donald Trump. If it turned out that kissing Donald Trump's giant orange backside cured COVID, scientists would be the first ones telling people to line up and use chapstick.

The other camp's response has ranged from undisguised glee -- that is, joy at the idea that we won't be saving lives cheaply -- to bizarre claims that Trump should be charged with crimes for touting this unproven therapy.

(A perfect illustration of the dementia: former FDA Head Scott Gottlieb -- who has been a Godsend for objective analysis during the pandemic -- tweeted out the results of the RECOVERY unblinding yesterday morning and noted that it showed no increased safety risk. He was immediately dogpiled by one side insisting he was trying to conceal the miracle cure of HCQ and the other insisting he is a Trumpist doing the Orange Man's dirty work.)

In the end, the lunatics do not matter. Whether HCQ works or not, whether it is used or not, will be mostly determined by doctors and will mostly be based on the evidence we have in front of us. If HCQ fails -- and it's not looking good -- my only response will be massive disappointment. Had HCQ worked, it would have been a gift from the heavens. It is a well-known, well-studied drug that can be manufactured cheaply in bulk. Had it worked, we could have saved thousands of lives, prevented hundreds of thousands of long-term injuries and saved trillions of dollars. That it doesn't appear to work -- certainly not miraculously -- is not entirely unexpected but is also a tragedy.