The Food and Drug Administration (FDA) has approved hydroxychloroquine—a drug used to treat malaria, rheumatic diseases and other conditions—for COVID-19.

As the COVID-19 pandemic spreads around the world, scientists are scrambling to identify treatments that may be effective against the disease. Hydroxychloroquine—a common derivative of chloroquine—is among those touted as most promising by some experts.

"The nice part is, it's been around for a long time, so we know that if things don't go as planned its not going to kill anybody," Trump told reporters at a press conference. "When you go with a brand new drug, you don't know if that's going to happen. Its shown very very encouraging early results and we're going to be able to make that drug available almost immediately."

But how effective is the drug? This week, researcher Didier Raoult from Aix-Marseille University in France, one of the main proponents for using hydroxychloroquine to treat infection with the novel coronavirus—known as SARS-CoV-2—released encouraging results of a preliminary trial involving a total of 36 COVID-19 patients.

Between early and mid-March, Raoult and his team treated 20 of these patients with 600 milligrams of hydroxychloroquine daily in a hospital setting. Depending on their symptoms, an antibiotic known as azithromycin was also added to the treatments. This antibiotic is known to be effective against complications from bacterial lung disease. The 16 remaining patients were not given the drug as a control.

In the study, the scientists observed a "significant" reduction in viral load in the patients treated with hydroxychloroquine, and that the effect was reinforced by azithromycin, Medscape reported.

In fact, after six days, 70 percent of the treated patients were considered cured, meaning that the virus was no longer detected in samples taken from them, compared to 12.5 percent of the control group patients. Furthermore, all six patients who were treated with both hydroxychloroquine and the antibiotic azithromycin tested negative for the virus after six days.

While encouraging, it is important to note that this is an unpublished preliminary study, so the results should be viewed with caution. The sample size is small, and the study was non-randomized, meaning people were allocated to different interventions using non-random methods. The study was also "unblinded," meaning that all parties—i.e. the medical staff, patients and researchers—were aware of the treatments the participants received.

Randomization and blinding—where one or more parties are kept unaware of which treatments patients received—are used to prevent conscious or unconscious bias from affecting the results of the trial. Nevertheless, Raoult and colleagues decided to publicly release their early results due to the unprecedented nature of the COVID-19 outbreak.

"For ethical reasons and because our first results are so significant and evident we decide to
share our findings with the medical community, given the urgent need for an effective drug
against SARS-CoV-2 in the current pandemic context," the authors wrote in the draft paper.

Some experts—such as Andrew Preston from the University of Bath in the U.K.—stress that larger, controlled trials need to be conducted to truly determine the effectiveness of hydroxychloroquine as a treatment for COVID-19.

"Remarkably, this study finished on March 16, but the group have released their results publicly in the hope of stimulating other studies to establish larger data sets," Preston said in a statement provided Science Media Centre U.K. "This rapid and open release of data is typical of the response to the COVID-19 pandemic, and recognizes the urgent and desperate need for any tool that might help treat patients and stem the tide of infection."

"The results have yet to be fully scrutinized, and of course, it is essential to conduct other, larger controlled trials to determine accurately the effectiveness of [the drug] as a treatment for COVID-19. But in among the oppressive darkness of the current situation, any glimmer of hope is very welcome."

Raoult's study—the first to test hydroxychloroquine on patients—follows some promising research from China. One preliminary trial involving 100 patients indicated that chloroquine was effective in the treatment of COVID-19-related pneumonia, without the presence of severe side effects, according to a paper published in the journal BioScience Trends. Other in vitro research—tests conducted using cells in test tubes rather than inside patients—also indicated the potential efficacy of chloroquine.

According to Raoult, the effect of both chloroquine and its derivative hydroxychloroquine is probably the same since the mechanism of action of these two closely-related molecules is identical, he noted in a study published in the International Journal of Antimicrobial Agents. For around a decade, studies have reported potential anti-viral properties of these two substances against flu and SARS—another form of coronavirus.

With regards to hydroxychloroquine specifically, more encouraging in vitro results emerged in a paper published on March 9, in the journal Clinical Infectious Diseases. However, the data was not deemed sufficient by infectious disease experts to recommend the compound as a treatment yet, Medscape reported.

Christian Perronne, head of infectious diseases, University Hospital Raymond Poincaré, Garches, Paris, is enthusiastic about the potential of hydroxychloroquine to treat COVID-19.

"I really believe in hydroxychloroquine. It is a drug I find rather fascinating, that has been used for decades," he told Medscape. "This could reduce the number of carriers, which I find interesting from an epidemiological perspective."

"I think from an ethical point of view, we should suggest it to all patients with severe disease who are hospitalized, under surveillance and on short treatment," he said. "Afterwards, in terms of adverse effects, at increased doses, it is possible that patients will have pain or fever, but it seems that the treatment is effective at lower doses, according to the Chinese data. In any case, the adverse effects of this compound are not dangerous."

Thomas Papo from Bichat Hospital, the University of Paris, noted that because the drug has been used for decades, we know lots about it.

"Hydroxychloroquine, vaunted by Didier Raoult as an anti-viral, has been used for decades in tens of thousands of patients, for several decades, so we have a huge follow-up and lots of data. This drug is remarkably well tolerated and we give it to all patients with lupus (for example), including in pregnant women. The main complication (retinal toxicity) is rare and does not last beyond 5 years of continuous use," he told Medscape.

Because the safety of hydroxychloroquine is well-established this should theoretically make it relatively easy to accelerate development into a treatment for COVID-19 if clinical trials are successful, especially given that it is cheap and not difficult to manufacture. Scientists will continue to conduct trials of the substance in the immediate future. For example, Raoult's trial in Marseille is being extended.

Nevertheless, some experts such as Gilles Pialoux, an infectious disease specialist at Tenon Hospital, France, are more cautious over hydroxychloroquine, noting that there are potentially more promising treatments available, such as a drug called remdesivir.

Another potential antiviral treatment for COVID-19 known as Kaletrea—a combination of two drugs normally used to treat HIV, lopinavir and ritonavir—has turned out to be ineffective for the treatment of severe illness with SARS-CoV-2.

According to a paper published in The New England Journal of Medicine, which involved 199 patients—99 of whom were given Kaletra—at a hospital in Wuhan, China, the treatment produced no observable benefit beyond standard care procedures. However, the researchers note that more research is needed to determine whether or not this treatment is effective against the virus.

"Future trials in patients with severe illness may help to confirm or exclude the possibility of a treatment benefit," the authors wrote in the study.