Why Does the President Keep Pushing a Malaria Drug?

What is actually known about hydroxychloroquine, the medication that Trump is fixated on recommending for COVID-19

The Atlantic

Two weeks ago, French doctors published a provocative observation in a microbiology journal. In the absence of a known treatment for COVID-19, the doctors had taken to experimentation with a potent drug known as hydroxychloroquine. For decades, the drug has been used to treat malaria—which is caused by a parasite, not a virus. In six patients with COVID-19, the doctors combined hydroxychloroquine with azithromycin (known to many as “Z-Pak,” an antibiotic that kills bacteria, not viruses) and reported that after six days of this regimen, all six people tested negative for the virus.

The report caught the eye of the celebrity doctor Mehmet Oz, who has since appeared on Fox News to talk about hydroxychloroquine 21 times. As Oz put it to Sean Hannity, “This French doctor, [Didier] Raoult, a very famous infectious-disease specialist, had done some interesting work at a pilot study showing that he could get rid of the virus in six days in 100 percent of the patients he treated.” Raoult has made news in recent years as a pan-disciplinary provocateur; he has questioned climate change and Darwinian evolution. On January 21, at the height of the coronavirus outbreak in China, Raoult said in a YouTube video, “The fact that people have died of coronavirus in China, you know, I don’t feel very concerned.” Last week, Oz, who has been advising the president on the coronavirus, described Raoult to Hannity as “very impressive.” Oz told Hannity that he had informed the White House as much.

Anthony Fauci is not among the impressed. The day the study came out, Fauci, the leading infectious-disease expert advising the White House’s coronavirus task force, downplayed the findings as “anecdotal.” The report was not a randomized clinical trial—one in which many people are followed to see how their health fares, not simply whether a virus is detectable. And Oz’s “100 percent” interpretation involves conspicuous omissions. According to the study itself, three other patients who received hydroxychloroquine were too sick to be tested for the virus by day six (they were intubated in the ICU). Another had a bad reaction to the drug and stopped taking it. Another was not tested because, by day six, he had died.

Nonetheless, the day after Raoult’s study was published, Donald Trump tweeted about it: “HYDROXYCHLOROQUINE & AZITHROMYCIN, taken together, have a real chance to be one of the biggest game changers in the history of medicine.” In the days since, Trump has repeatedly returned to this claim. On Saturday, he said that the term game changer wouldn’t even adequately describe the drug: “It will be wonderful. It will be so beautiful. It will be a gift from heaven, if it works.” After downplaying the value of ventilators and social distancing, measures that experts overwhelmingly agree are needed to overcome the virus, Trump said the country would procure 29 million doses of hydroxychloroquine for a national stockpile. He said he may start taking the drug himself.

Over the course of these two weeks, the president of the United States has become the world’s most prominent peddler of medical misinformation. While some very early evidence has shown that hydroxychloroquine may influence the course of COVID-19, Trump is overriding his top medical adviser and minimizing serious risks by encouraging Americans to try the drug right now. This brazen dispensation of medical advice from the president is dangerous in ways beyond the potential harm of the drug itself. A time of strict directives for personal behavior and hygiene requires tremendous trust in those giving the directives—and understanding the reality that this is a disease without a miracle cure. But instead of inspiring trust, Trump has pivoted from downplaying the number of cases in the United States to the extremely effective trick of quack medical providers: hyping an unproven treatment that entices desperate people with false confidence and confusing messaging.

It is unclear how hydroxychloroquine would work to treat COVID-19, but the drug is one of many now being urgently studied for the treatment of the disease. The drugs being tested include those that could block viral replication, such as remdesivir, and others that may target the way the virus binds to human cells. Still other drugs aim to modulate a person’s immune response, among them a class of drugs known as IL-6 inhibitors. Hydroxychloroquine has the theoretical potential to affect the virus itself or the immune response. In addition to treating malaria, hydroxychloroquine is important in the treatment of autoimmune diseases such as rheumatoid arthritis and lupus. In those specific conditions, the drug effectively serves to subdue an overactive immune response.

Slowing the immune system too far, though, could make people more susceptible to infection. Other drugs that suppress inflammation—steroids and ibuprofen—initially generated some enthusiasm as methods of controlling the immune response in COVID-19. They have since shown mixed results and are not widely recommended. Even in people without the disease, hydroxychloroquine’s potentially harmful effects range from vomiting and headaches to instances of psychosis, loss of vision, and even sudden cardiac death. The drug is to be used with caution in people with heart conditions and liver dysfunctionboth of which the coronavirus can itself cause.

Based on the limited evidence so far, giving hydroxychloroquine to people could very well be—as with most drugs that modulate the immune system—of some benefit in some circumstances. Some people will be made sicker by it, depending on underlying physiology, other medications they’re taking, timing, and dosing. Identifying who stands to benefit and why requires data, and several randomized controlled studies of hydroxychloroquine are under way.

But Trump has plunged ahead. On March 28, amid his constant enthusiasm, the FDA issued an emergency authorization allowing the use of hydroxychloroquine for treatment of COVID-19. Even still, the agency urged that the drug should be given only to patients “for whom a clinical trial is not available, or participation is not feasible.”

Some hospitals in the U.S., including Massachusetts General Hospital, have begun incorporating hydroxychloroquine into treatment protocols, at the discretion of an infectious-disease specialist. Other institutions are more guarded. At the University of Washington, doctors are advised in official treatment policy that although the drug has been shown to inhibit replication of the virus in cultures of monkey kidney cells, “it has not been shown to be an effective antiviral” in living organisms. The University of Michigan Medical School advises its doctors that “the current body of literature and local experience does not support the routine use of any specific treatment regimen, including hydroxychloroquine, for patients with confirmed COVID-19 infection.”

Conclusions like these draw on the fact that the body of evidence remains small, and the results are mixed. A randomized trial of 30 patients with COVID-19 in Shanghai found no difference in detectable virus at day seven, with or without hydroxychloroquine. Another recent study suggested that the drug may help with COVID-19 symptoms, including coughing and fever, but it included only 62 people with mild cases of the disease, and excluded anyone with conditions that could be exacerbated by hydroxychloroquine. In mid-March, Italian and Israeli researchers concluded that there were sufficient grounds to continue doing research with the drug, but that any use should be closely monitored. The scientists advised against widely unleashing yet another medical variable during the pandemic.

In the U.S., Fauci continues to hold the same line as the rest of the medical community—cautious optimism, with a close eye on the many ongoing clinical trials. Trump, meanwhile, escalates as a peddler. “What do you have to lose?” the president said in a press conference on Saturday. “I’ll say it again: What do you have to lose? Take it. I really think they should take it. But it’s their choice. And it’s their doctor’s choice, or the doctors in the hospital.” At a briefing yesterday, he intercepted a question for Fauci about hydroxychloroquine and told the reporter that the doctor wouldn’t be answering it.

What do you have to lose? is a dark sentiment from a president managing a crisis that his administration failed to prepare for: It failed to develop testing, failed to communicate, and failed to have enough face masks for doctors. There is, in fact, much to lose. Americans also need hydroxychloroquine to treat serious immune conditions and parasitic diseases. Since Trump began promoting the drug, people have been hoarding it, and it has been added to the growing list of drug shortages. Two weeks ago, in an attempt to procure some, an Arizona couple ingested chloroquine, which is meant to be used in fish tanks. The man died.

In such moments, the appeal of any treatment that could offer a glimmer of hope is understandable. But even if hydroxychloroquine eventually proves to be safe and useful to some people with the disease, touting it constantly distracts from the immediate needs of the crisis. Now is not a time to abandon the tried and true systems that keep people safe and create order. It’s a time to double down on the systems developed over decades to help us find the best treatments for diseases, and make sure that they are safe and effective. What do you have to lose? follows the logic of removing stop signs because they might slow people trying to get to the hospital.

In his capricious responses to this pandemic, Trump has given little indication that he respects, or even comprehends, the reasons for the scientific process. Hydroxychloroquine could end up as part of the treatment approach that one day saves lives. Outside of a proper testing process and clear messaging, it could cost lives. Addressing a world in a collective state of despair, Trump offers exaggerated hope and endangers people as he rambles.

On Saturday, Trump suggested research exists that shows people with lupus don’t get the coronavirus, implying that their use of hydroxychloroquine protects them. “There’s a rumor out there that because it takes care of lupus very effectively, as I understand it, and it’s a, you know, a drug that’s used for lupus,” he said, “so there’s a study out there that says people that have lupus haven’t been catching this virus. Maybe it’s true; maybe it’s not.”

There is no such study.

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