What if hydroxychloroquine doesn’t work? What if it does? We don’t know yet

An old malaria medicine, hydroxychloroquine, has gone viral on the internet. But is it really an antiviral drug?
The medicine has been seen as a potential treatment for Covid-19, the disease caused by the novel coronavirus SARS-CoV-2, almost since outbreaks started. This week it made headlines, due in part to tweets from President Trump and in part because of a small French study of 42 patients that seemed to show that hydroxychloroquine, particularly when combined with the antibiotic azithromycin, helped decrease patients’ levels of coronavirus. Unfortunately, the rumors about the drug’s efficacy have also encouraged some to buy and even consume a similarly named fish tank cleaner; one person has died.
But a second study emerged last week from Shanghai University in China of 30 patients hospitalized for Covid-19. Whether patients received hydroxychloroquine or not, their body temperature returned to normal a day after hospitalization, and the time it took for levels of the virus to become undetectable was comparable. Unlike the study from France, the patients in this study were randomly assigned to either hydroxychloroquine or the control group, which makes the results more reliable.

Jun Chen, one of the authors of the Shanghai study, called the French study’s results “interesting” but said they needed to be evaluated in another randomized study.
“Both our study and theirs had many limitations,” Chen wrote. “But personally, I would say that hydroxychloroquine was not a ‘magic’ drug, if there is any antiviral effect. And in fact, hydroxychloroquine has never been effective in any viral diseases, despite its in vitro antiviral activity.” “In vitro antiviral activity” means that the drug stops the virus from infecting cells in the dish.

The first mention of the Shanghai study came from a paper in The Lancet Global Health, where the results were described as positive. One of the authors of the Lancet paper, Oriol Mitjà, wrote via email that changes on CT scans showed “that the drug has some efficacy” against Covid-19. In the Shanghai study, worsening of the disease that could be picked up on a CT scan happened in 33% of those on hydroxychloroquine (that’s 5 patients) versus 47% of those in the control group (7 patients).
Mitjà was even more optimistic about the French study, saying it has “new and stronger data.”
But objections have been raised to the French study  paper, even as it’s bounced around the Internet. Fox host Sean Hannity even shared another doctor’s letter on his experience using the hydroxychloroquine/azithromycin combination on his television show on March 23.
Three statisticians published a review of the French study that argued that the way it was designed made the treatments look better than they actually are. They pointed to the lack of randomization, as well as an inappropriate control group composed partly of people who refused to take the drug. They also noted that the study dropped some patients from the analysis — the small study of 42 patients actually only included data from 36. The Shanghai study, which showed less impact from the treatments, adds to the questions about the French study, wrote Tim Morris, a statistician at the MRC clinical trials unit at University College, London.
“The [French] study gave very little useful information about whether hydroxychloroquine might help,” Morris wrote. “The Shanghai study is better (because they had a meaningful control group) but gives us very little information that hydroxychloroquine doesn’t help.” The data, he wrote, are “compatible with a wide range of possible effects,” which is statistician-speak for, “Nobody knows whether the drug helps or not.”
The Shanghai study, Morris wrote, is a step in the right direction toward some bigger, better trials that are kicking off. The first of these might give some answers in April — a short time when it comes to clinical trials, but potentially after the United States, and particularly New York City, will have seen a tsunami of Covid-19 cases.

What if hydroxychloroquine doesn’t work? What if it does? Right now, we don’t know