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No specific treatment yet exists for COVID-19. But along with other medical centers, Yale Medicine doctors and researchers are testing several drugs, including one that is regularly used to treat malaria, at Yale New Haven Hospital.
Not enough data has been gathered yet to know how effectively any of these drugs work, says Joseph Vinetz, MD, an infectious disease specialist who is treating COVID-19 patients.
Doctors are still learning how COVID-19 can cause respiratory distress and trigger a dangerously overactive immune response, Dr. Vinetz says.
However, President Trump mentioned in a March 19 news briefing that two malaria drugs, hydroxychloroquine and chloroquine, have “tremendous promise” as treatments for COVID-19, and, in a tweet, he referred to a small study of patients in France as supporting evidence. President Trump has also pointed to the antibiotic azithromycin (also known as a Z-Pak) as a potential treatment.
“There’s no strong or even moderate evidence for azithromycin as a medicine to help the immune system,” Dr. Vinetz says. Several days later, the same French research team released a second study showing results similar to the first. But Dr. Vinetz says both studies were too small and poorly designed to offer anything besides anecdotal evidence. “The director of the more recent French study of 80 patients from the same clinical research group indicated that, for ethical reasons, no control was included,” Dr. Vinetz says. “This study reported that virus positivity went away over about a week or so in treated patients.”
A surge in prescription requests for hydroxychloroquine and azithromycin
In the days following President Trump’s tweet that hydroxychloroquine plus azithromycin were useful for treating COVID-19, pharmacies across the U.S. reported a surge in prescription requests from doctors apparently stockpiling the drugs, according to news reports. State pharmacy boards quickly began enforcing restrictions on how many prescriptions of the medicines could be filled.
The Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) have stated that there are no drugs approved for treating COVID-19. However, in an attempt to test the effectiveness of anti-malaria drugs on COVID-19, on March 28 the FDA issued an Emergency Use Authorization (EUA) to “allow hydroxychloroquine sulfate and chloroquine phosphate products donated to the Strategic National Stockpile to be distributed and prescribed by doctors to hospitalized teen and adult patients with COVID-19, as appropriate, when a clinical trial is not available or feasible,” according to a statement released by the U.S. Department of Health and Human Services.
(The EUA also requires fact sheets that provide important information about using chloroquine phosphate and hydroxychloroquine sulfate in treating COVID-19, including the known risks and drug interactions, be made available to health care providers and patients.)
On March 29, Sandoz, the generic division of Novartis, donated 30 million doses of hydroxychloroquine, and Bayer Pharmaceuticals donated 1 million doses of chloroquine (another anti-malaria drug) to the country’s national stockpile to potentially treat patients hospitalized with COVID-19 or for use in clinical trials.
What is hydroxychloroquine?
Besides its anti-malarial effects, hydroxychloroquine (brand name Plaquenil) is FDA-approved to treat lupus and rheumatoid arthritis. “Because it seems to dampen the immune response, we use it for those conditions,” Dr. Vinetz says. “But you cannot give too much of it because of the risk of cardiotoxicity—so it must be very carefully controlled.” Cardiotoxicity means that the drug can cause heart damage in different ways, for example, through irregular heartbeats or reduced blood flow to the heart. Long-term use of hydroxychloroquine is also linked to damage to the retina, a membrane in the back of the eye, though that side effect is rare.
“But people are stockpiling hydroxychloroquine and taking it as a prophylactic,” Dr. Vinetz says, referring to a drug designed to prevent a disease from happening. (An example of prophylactic use of a drug is a patient undergoing surgery who might be prescribed antibiotics to prevent infection.) “There’s no evidence at all that hydroxychloroquine could prevent a person from becoming infected with SARS-CoV-2, the virus that causes COVID-19,” Dr. Vinetz says. “And no one should take the drug on their own.” He says the same is true of chloroquine at this point.
Still, due to its ability to calm an inflammatory immune response in autoimmune diseases, Yale doctors are giving hydroxychloroquine to some severely ill COVID-19 patients “because there are theoretical benefits,” Dr. Vinetz says. “It’s an effort to dampen the immune response that might cause a person’s lungs to become inflamed and damaged enough to require a ventilator to breathe,” he explains. “It’s not an anti-viral.”
“Understanding what we call the natural history of infection, we’re doing various kinds of blood tests and other clinical assessments to try to prevent the hyper-inflammatory response from continuing,” Dr. Vinetz says.
Besides hydroxychloroquine, Yale doctors are trying tocilizumab (brand name Actemra) on patients who have COVID-19-induced pneumonia. Roche/Genentech, which makes the drug—given via intravenous infusion—recently announced that the FDA has approved a Phase III clinical trial testing tocilizumab, which means that it is now being tested in patients for this particular application. “We’re encouraged by it, although we don’t have data yet,” Dr. Vinetz says.
Among its other uses, tocilizumab is FDA-approved for a condition called cytokine release syndrome, a severe inflammatory response in the body that can be triggered by a cancer immunotherapy called CAR T-cell therapy.