Although there are no proven cures or treatments for COVID-19, the respiratory illness caused by the novel coronavirus, one drug has drawn more attention and controversy than the rest: the antimalarial drug hydroxychloroquine. Touted as a potential “game changer” by President Trump, the drug has gained widespread use as an experimental therapy for COVID-19 patients, despite meager evidence of its effectiveness.
In the rush to treat a growing wave of stricken patients, several hospitals in Boston, including Mass. General, Boston Medical Center, and Tufts Medical Center, are administering hydroxychloroquine, sometimes in combination with the antibiotic azithromycin, based on test-tube studies and anecdotal reports from doctors in China, Italy, and France, who have said the drug seemed to help infected patients improve. Doctors say the unprecedented crisis has forced them to balance the need for evidence-based treatment with the on-the-ground realities of a fast-moving pandemic.
“We have been looking at the evidence very carefully, and so far, there’s not a whole lot of evidence — meaning well-defined clinical studies — that argue for or against the use of hydroxychloroquine," said Dr. Brian Chow, an infectious diseases specialist at Tufts Medical Center. “But we’ve been following the same news reports and following the same stories as everybody has, and we’re using it as one part of our arsenal.”
Hydroxychloroquine is a safer derivative of chloroquine, a synthetic drug discovered by German scientists in 1934 and field-tested by the US Army in World War II for the prevention and treatment of malaria. In the United States, hydroxychloroquine is primarily prescribed for treating autoimmune diseases like rheumatoid arthritis and lupus due to its anti-inflammatory properties, which is why some scientists believe it could be useful for treating COVID-19. In some critical cases of the disease, the body’s immune system overreacts, triggering a perilous inflammatory response that can threaten the lungs and other organs.
In laboratory tests, chloroquine and hydroxychloroquine have also demonstrated antiviral activities against other viruses, including Ebola, Zika, influenza, and SARS, according to Dr. Raghu Chivukula, a pulmonary and critical care physician at Massachusetts General Hospital. But they have repeatedly failed to benefit patients with similar diseases in clinical trials, he said.
"Even though they seem to have promise in culture and in the laboratory, [they] really haven’t performed that well out in the wild in the years we’ve tried them for other diseases that are relatively similar,” Chivukula said. "And so it does give you some pause about using them without really, really good evidence they’re actually going to do something in COVID-19.”
“No one would be happier than us if these drugs ended up being very effective, but I don’t think anyone in good conscience can say that yet,” Chivukula added. “It’s really about balancing the potential for benefit with the potential for harm, and the potential for benefit is unknown right now. The potential for harm is not high, but it’s not zero either.”
Hydroxychloroquine is far from the only experimental therapy doctors are using to treat COVID-19 patients. In addition to the mad dash to develop a vaccine for the virus — an effort experts expect will take 12 to 18 months before one becomes commercially available — researchers and drug companies are conducting trials of remdesivir, an antiviral medication originally tested on Ebola patients; ritonavir and lopinavir, a combination therapy for treating HIV; and the immune system inhibitors tocilizumab and sarilumab, among others.
But the antimalarial drugs have dominated the national conversation, along with much of the new research on coronavirus treatment and prevention, likely due to the president’s enthusiastic advocacy for the drugs. (According to The New York Times, Trump has a small financial stake in the French company Sanofi that manufactures Plaquenil, the brand name for hydroxychloroquine.)
Dozens of clinical trials assessing hydroxychloroquine’s effectiveness as a COVID-19 treatment are underway around the world. Mass. General is sponsoring a placebo controlled study, in collaboration with the National Institutes of Health, that plans to test hydroxychloroquine on 510 patients hospitalized with COVID-19 at 44 institutions across the country, including Beth Israel Deaconess, Baystate Medical Center in Springfield, and St. Vincent’s Hospital in Worcester.
For hospitalized patients with the disease for whom clinical trials are not available, the Food and Drug Administration has authorized the emergency use of hydroxychloroquine and chloroquine, using doses from the Strategic National Stockpile. At a press briefing earlier this month, Trump said the federal government had procured 29 million doses of hydroxychloroquine. According to the Federal Emergency Management Agency, more than 19 million tablets from the stockpile have been distributed to cities since April 6.
But at least one hospital in Massachusetts had started stocking up on the drug before Trump became its cheerleader. In early March, Dr. Tamar Barlam, the chief of infectious diseases at Boston Medical Center, said her hospital placed an order “for as much [hydroxychloroquine] as we could get, so that if we wished to use it, we would have that option.” BMC has since treated more than 200 COVID-19 patients with hydroxychloroquine, she said.
“We were getting direct reports from China and Italy, so we knew ahead of President Trump speaking about [hydroxychloroquine] that this was something that is being tried,” she said.
The drug was initially used on patients who were having trouble breathing, Barlam said, but “that didn’t seem to show that it was of much value.” Now hydroxychloroquine is given to any patient at BMC who tests positive in the emergency department, early in the course of their treatment. It’s still an open question, she added, as to whether the drug has any benefit. So far, BMC doctors have found the drug is well-tolerated by patients, she said, and they haven’t had any issues monitoring them for side effects.
“I think for all the intentions of hydroxychloroquine, even at Boston Medical Center where we did act quickly and started ordering it and using it, we never viewed it as this was going to be the answer, if you will," Barlam said.
“I just feel like the hype is overblown to say the least," she continued. "We’re [using] it because while we’re waiting for these rigorous trials, we want to feel like we’re offering patients an option that may actually be helpful. But the moment we see it’s not helpful — believe me — we will not use it.”
Taking hydroxychloroquine is not without risk. The drug can have severe side effects, particularly among people with heart conditions. Earlier this week, researchers in Brazil halted part of a small clinical trial testing chloroquine on 81 hospitalized COVID-19 patients after noticing participants taking high doses of the drug had developed dangerous heart arrhythmias. Eleven of the study’s participants on high dosages died.
Other recent studies testing chloroquine or hydroxychloroquine on COVID-19 patients have produced inconclusive or limited results due to their substandard quality and methodology. For example, experts have roundly criticized a highly publicized French study — endorsed by Trump on Twitter — that claimed to show the benefits of hydroxychloroquine and azithromycin on COVID-19 patients. The study, however, was marred by its small sample size and nonrandomized methods. The International Society of Antimicrobial Chemotherapy, which published the study online, later released a statement, saying the article did “not meet the Society’s expected standard.”
But recent enthusiasm for the unproven drug has prompted a run on both hydroxychloroquine and chloroquine, leading to shortages for patients with lupus and rheumatoid arthritis who rely on them for alleviating their symptoms. Some doctors and even dentists have begun improperly prescribing antimalarial medications for themselves, friends, and family, according to reports from pharmacy boards across the country. Others have dangerously tried to self-medicate: In Arizona, a man died after ingesting fish-tank cleaner containing chloroquine phosphate, believing it would protect him from contracting the coronavirus.
“People have stockpiled it for themselves — that’s one of the first things people did,” said Dr. Lauren Westafer, an emergency medicine physician at Baystate Medical Center. “These people, especially if they’re outpatients, [that means] they’re not being monitored. They could die.”
Westafer is not prescribing hydroxychloroquine for COVID-19 patients who arrive in her emergency department but are well enough to be sent home. Only coronavirus patients admitted to the hospital may be given the drug on a case-by-case basis, determined by a team of intensive care physicians and infectious disease specialists, she said.
But she’s worried the use of hydroxychloroquine has become part of the standard of care for treating COVID-19 patients despite the lack of scientific evidence to support it.
“We’re in an area where there’s very limited evidence and you get conflicting anecdotal experience and that’s why anecdote is so harmful,” Westafer said. “When you dilute the pool, when you give it to everybody who has the disease ... it’s going to look like there are better outcomes because you’re giving it to all kinds of people.”