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On March 20, researchers in France published in the International Journal of Antimicrobial Agents that hydroxychloroquine, a drug typically used to treat malaria and autoimmune disorders, was unbelievably effective at treating Covid-19 (emphasis on unbelievably), virtually curing people of the novel coronavirus in less than a week. The news took off, fueled by President Donald Trump’s uninformed enthusiasm for what he dubbed a miracle cure.

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Scientists quickly called for restraint, saying not enough was known about the drug — its efficacy and its risks — and perhaps the French data was a little too good to be true. Sure enough, there are numerous flaws in the study’s methods, most glaring that they excluded people in the analysis who received the drug but continued to decline, falsely inflating the efficacy of the medication.

More criticisms have since emerged: It turns out the senior author of the study, Didier Raoult, is also the editor-in-chief of the journal where it was published, a clear conflict of interest. Perhaps most scathing, the scientific society that publishes the journal, the International Society of Antimicrobial Chemotherapy, issued a statement that the article “does not meet the Society’s expected standard.”

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Despite the drama, it doesn’t mean that hydroxychloroquine, which can act as both an antiviral and immune-modifying agent, doesn’t work. A Chinese clinical trial of hydroxychloroquine that was released as a preprint paper on March 31 also reported positive results, although much more tempered. The researchers show that people with Covid-19 who received hydroxychloroquine recovered faster than people who did not, and after five days, more people with pneumonia had recovered if they received the treatment. In the U.S., the National Institutes of Health just launched its first placebo-controlled clinical trial to test hydroxychloroquine in 500 patients hospitalized with Covid-19.

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Doctors at many hospitals around the world have also been using hydroxychloroquine off-label to treat people with Covid-19 in the hope that it might have some effect against the novel coronavirus. However, new troubling information has emerged that the drug can have severe and potentially fatal side effects. There are news reports from Sweden that doctors there have stopped giving the drug to patients after a rash of severe side effects, including migraines, cramps, and vision loss. Hydroxychloroquine can also cause cardiac arrhythmias and heart disease at high doses. One man in Sweden reported taking four pills a day, twice the amount normally prescribed.

Even more concerning, there is new data — important caveat: in mice — that when combined with the common diabetes drug metformin, hydroxychloroquine was fatal in more than 30% of the animals. This report is particularly concerning given that people with diabetes are at a higher risk of severe illness and death from the virus.

Perhaps most interesting are anecdotal reports from doctors in New York and California who independently prescribed hydroxychloroquine in combination with zinc and claim to be seeing miraculous recoveries in their patients. The news first took off in right-wing media outlets not known for their scientific rigor, but there is basic biological evidence to suggest that the combination of the two drugs might be more effective than either one individually.

Zinc can act as an antiviral, including against other coronaviruses. However, the mineral does not penetrate cells very easily, so it’s largely ineffective against viruses when given on its own. However, if paired with another drug that can open up a channel in the cell, zinc can enter and block the virus from replicating. Hydroxychloroquine is one such drug that can open the zinc cellular channel, potentially combining the antiviral properties of zinc with those of hydroxychloroquine.

It’s important to remember that this research is preliminary, demonstrated either anecdotally in a small number of patients or in cellular studies conducted several years ago on other coronaviruses. There has not yet been any published data on the efficacy of the combination therapy to treat Covid-19. However, three clinical trials to test the two drugs are listed on clinicaltrials.gov, one that is enrolling in Turkey and two others in the U.S. proposed by the pharmaceutical company ProgenaBiome.

Until the results of these studies come out, do not take hydroxychloroquine if a doctor has not prescribed it to you (one man has already died from doing so), and do not ever hoard the drug, which can prevent those who actually need it from having access to it.

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