A Summary of Hydroxychloroquine Research

As I mentioned on Facebook, I was in an all day meeting yesterday, away from the interwebs. I emerged from said meeting to find the hydroxychloroquine debate raised from the dead on social media, with Twitter and Facebook feeds jam packed with articles flying from both sides, with people clamoring both for and against the drug yet again. In an effort to get on top of the debate, I took some time to look through the actual studies and see what’s been said, who said it, and why. And because I thought this might be helpful to some others, I’m presenting it here on the blog.

Before I get into that, a disclaimer that I think would be good for almost all of the people trying to insert themselves into this debate to remember: I am not a doctor. I am not an expert in this field. I can consume information and question its validity, and I can have a fair shot at piecing together unbiased sources and research to try to get to the bottom of things, but I lack the background to really be able to look at a scientific question like “is hydroxychloroquine effective” and be able to hope to answer it. That’s what we rely on other experts for.

And a second note about experts: as much as I might not like popularity contests in general, in science, it’s kind of the point. Science doesn’t work by finding the expert who agrees with the opinion you want to be true. It works by doing research, making findings, having people confirm that research with their own findings, and thus having the entire scientific community reach a general consensus around an issue. Yes, there will remain things in debate on the edges, but as a whole, scientific consensus gets us where we want to go, even if it might be more slowly than we’d like. Research takes time, or at least, good research does. You want to pay attention to how the studies were performed, how many subjects they involved, their rigor, etc.

I entered into the research for today’s issue with a simple question: “Is hydroxychloroquine an effective, safe treatment for COVID-19? If so, how widely can/should it be used?”

First, it’s good to check why the debate suddenly surged back to the forefront of the COVID discussion. From what I gather, it boils down to two articles/videos. The first is a video by Dr. Stella Immanuel and other doctors claiming hydroxychloroquine cures COVID and that taking it protects you from COVID. The second is an article in Newsweek from Dr. Harvey Risch, stating that when taken by high risk patients early in the disease, hydroxychloroquine is an effective treatment. (Immanuel makes some of the same disclaimers in her statement, but she pressed the issue further, implying there’s a “cure.”) Dr. Risch seems like a more solid source, judging from what I’ve read about Dr. Immanuel, but let’s set aside their histories for the moment and look specifically at the claims. Have more studies been done that prove what these doctors are saying?

Here’s a rundown of the studies I’ve found.

Date	# of Patients	Conclusions	Link
July 23	667	“Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care.”	Study
July 16	423	“Hydroxychloroquine did not substantially reduce symptom severity in outpatients with early, mild COVID-19” (second study in Spain had similar results)	Study
July 1	2,541	“In this multi-hospital assessment, when controlling for COVID-19 risk factors, treatment with hydroxychloroquine alone and in combination with azithromycin was associated with reduction in COVID-19 associated mortality. Prospective trials are needed to examine this impact”	Study
July 1	FDA Review	“A summary of the FDA review of safety issues with the use of hydroxychloroquine and chloroquine to treat hospitalized patients with COVID-19 is now available. This includes reports of serious heart rhythm problems and other safety issues, including blood and lymph system disorders, kidney injuries, and liver problems and failure.”	Review
June 20	500	“A data and safety monitoring board (DSMB) met late Friday and determined that while there was no harm, the study drug was very unlikely to be beneficial to hospitalized patients with COVID-19.”	Results
June 18	1,446	“In this observational study involving patients with Covid-19 who had been admitted to the hospital, hydroxychloroquine administration was not associated with either a greatly lowered or an increased risk of the composite end point of intubation or death. Randomized, controlled trials of hydroxychloroquine in patients with Covid-19 are needed.”	Study
June 15	2,300	“There was no significant difference between the number of people in each group who developed COVID-19”	Release
June 5	4,674	“These data convincingly rule out any meaningful mortality benefit of hydroxychloroquine in patients hospitalised with COVID-19. Full results will be made available as soon as possible”	Release
June 3	821	“After high-risk or moderate-risk exposure to Covid-19, hydroxychloroquine did not prevent illness compatible with Covid-19 or confirmed infection when used as postexposure prophylaxis within 4 days after exposure.”	Study
28 May	Meta-analysis	“The results of efficacy and safety of HCQ in COVID-19, as obtained from the clinical studies, are not satisfactory, although many of these studies had major methodological limitations. Stronger evidence from well-designed robust randomized clinical trials is required before conclusively determining the role of HCQ in the treatment of COVID-19. Clinical prudence is required in advocating HCQ as a therapeutic armamentarium in COVID-19.”	Release
May 27	Meta-analysis	“These medications need to be widely available and promoted immediately for physicians to prescribe.” (There’s also a response to this analysis saying “We strongly think that there is no convincing evidence to support the claim made by Risch”, as well as a response to that response where Risch defends himself.)	Study
May 27	Meta-analysis	“Evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19 is very weak and conflicting.”	Release
May 22	96,032	“Large Multinational Cohort Study Finds the Use of Macrolide Antibiotics, Hydroxychloroquine, or Chloroquine Is Not Associated with Better Outcomes but Is Associated with Increased Harms.” NOTE: This study was retracted by the Lancet because the researchers wouldn’t fully share their data	Study
May 14	150	“Administration of hydroxychloroquine did not result in a significantly higher probability of negative conversion than standard of care alone in patients admitted to hospital with mainly persistent mild to moderate covid-19. Adverse events were higher in hydroxychloroquine recipients than in non-recipients.”	Study
May 11	1,438	“Among patients hospitalized with COVID-19, treatment with hydroxychloroquine, azithromycin, or both was not associated with significantly lower in-hospital mortality.”	Study
May 5	181	“Hydroxychloroquine has received worldwide attention as a potential treatment for covid-19 because of positive results from small studies. However, the results of this study do not support its use in patients admitted to hospital with covid-19 who require oxygen.”	Study
April 23	368	“In this study, we found no evidence that use of hydroxychloroquine, either with or without azithromycin, reduced the risk of mechanical ventilation in patients hospitalized with Covid-19. An association of increased overall mortality was identified in patients treated with hydroxychloroquine alone. These findings highlight the importance of awaiting the results of ongoing prospective, randomized, controlled studies before widespread adoption of these drugs.”	Study

After looking at all these different studies, the conclusion I reach is that more studies should be done, as suggested by the research. It does appear that if taken at lower doses, there’s a chance that hydroxychloroquine can have a positive impact. But the bottom line is that we just don’t know that from the science, and any doctor making claims to the contrary is being downright misleading, no matter how well-intended they might be. Hydroxychloroquine does not seem to be a cure.

As another side note, I find it interesting so many are looking to a drug for a cure while ignoring the obvious “wear a mask.” In Breitbart’s video (where Dr. Immanuel speaks), none of the doctors are wearing a mask. They’re not standing six feet apart. I suppose you could argue that’s because they’re just that confident that hydroxychloroquine has cured them, but I look at other root causes that might explain that a little more fully. “America’s Frontline Doctors,” as they call themselves, are funded by the Tea Party Patriots and actively speaking out against the lockdown measures. These are people with an axe to grind, not necessarily a country to save.

And here’s the kicker: we know exactly what we could do to stop this pandemic in America. It’s been done in many other countries around the world. This article sums it up well, but it boils down to having 6 weeks of real lockdown measures, stopping interstate travel, mandating masks, and quarantining cases aggressively. All the debate about miracle cures makes me think about someone running around the deck of a sinking boat, talking about experimental flotation devices, while a plug to the hole in the boat is sitting right next to them.

If a loved one caught COVID, what would I do? I’d certainly bring up hydroxychloroquine to see if it might be of some help or at least be worth a shot. The science certainly hasn’t said it harms people who take it at appropriate dose levels. But I’m also wearing a mask and following social distancing suggestions, because I don’t want loved ones to have to be in that situation. Every minute we sit around dithering about hydroxychloroquine, we’re not paying attention to the simple measures that can and should be taken to make us safe. Now.

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