Politics aside, hydroxychloroquine could (maybe) help fight COVID-19

President Donald Trump’s announcement that he is taking the drug hydroxychloroquine as a precaution against the coronavirus has once again thrown a decades-old antimalarial drug into the headlines.

There’s currently not enough data to say whether the drug can protect people from catching COVID-19 or from getting very ill if they do get infected with the virus. Studies of its use in treating very sick patients have shown mixed results and, in some cases, have led to dangerous side effects.

But now, with the president touting hydroxychloroquine even as scientists issue cautions about its use, the drug has found itself at the center of political divides, to the possible detriment of figuring out whether it works.

Nevertheless, researchers are busy testing hydroxychloroquine and a related drug called chloroquine to see if they can either prevent infection or keep illness from worsening. Nearly 200 clinical trials are under way or planned around the world to test the drugs, either alone or in combination with other medications. That includes at least 28 trials examining whether either drug can protect healthcare workers and others at high risk of getting COVID-19.

Here’s what scientists know about the drugs and their potential.

Why do researchers think chloroquine or hydroxychloroquine may prevent coronavirus infections?

Both are antimalarial drugs that also have well-known antiviral activity against many viruses, including SARS and MERS. At least they work against those viruses in lab dishes.

In lab tests, hydroxychloroquine can also stop SARS-CoV-2, the coronavirus that causes COVID-19, from infecting cells and decreases replication of viruses that do get inside cells, researchers report March 18 in Cell Reports. A February 4 report in Cell Research found that chloroquine also inhibits the virus.

The drugs are thought to block viruses from entering cells by changing the pH, or acidity, of cellular compartments called lysosomes. That “creates a less friendly environment for the virus, so it might be more difficult for the virus to get into human cells in the first place,” says Michael Avidan, an anesthesiologist at Washington University School of Medicine in St. Louis. Avidan is involved in a clinical trial testing whether chloroquine can protect healthcare workers from infection or from developing serious disease.

In addition, hydroxychloroquine and chloroquine disrupt interactions between some of SARS-CoV-2’s proteins with proteins called sigma receptors in human cells, researchers report April 30 in Nature. Interrupting those protein interactions may make it difficult for the virus to replicate, says study coauthor Adolfo Garcia-Sastre, a microbiologist who directs the Global Health and Emerging Pathogens Institute of Icahn School of Medicine at Mount Sinai in New York City.

Together, those antiviral capabilities make the drugs attractive for use against the coronavirus. But there’s another important reason chloroquine and hydroxychloroquine were some of the first drugs pressed into action: They’re available. Doctors have been prescribing the drugs, already approved by the U.S. Food and Drug Administration, for decades and they’re generally safe, although there are some serious side effects.

“Time is of the essence,” says Adam Spivak, an infectious-disease doctor at the University of Utah in Salt Lake City. “When you have a drug that you understand and can safely administer that’s on the shelf, that’s the drug you reach for first.”

Hydroxychloroquine is better tolerated by most people, so is the one researchers are testing more often.

But isn’t taking hydroxychloroquine or chloroquine dangerous?
It can be for some people, such as those prone to heart problems, or when taken in combination with other drugs that can alter heart rhythms.

While hydroxychloroquine latches on sigma receptors proteins that are used by the virus, it can also bind to other proteins in the heart, Garcia-Sastre said in a news conference May 15. “It may not be the best drug that we can use right now to inhibit viral replication in people because of this.” Some other drugs also interrupt the coronavirus’s interactions with sigma receptors, but don’t bind to the heart proteins, which may make them safer alternatives to hydroxychloroquine, Garcia-Sastre said (SN: 4/30/20).

In trials with very sick people, hydroxychloroquine has caused sometimes fatal heart-rhythm problems. People with existing heart problems, those with low potassium levels or low oxygen levels in their blood are especially vulnerable to these serious side effects, says Raymond Woosley, a pharmacologist the University of Arizona in Phoenix.

The largest study to date, published May 22 in the Lancet, found that the drugs raised the risk of death for hospitalized COVID-19 patients. The findings are based on data from more than 96,000 coronavirus patients in 671 hospitals on six continents. Of those, nearly 15,000 received either chloroquine or hydroxychloroquine, either alone or in combination with a type of antibiotic called macrolides — usually azithromycin.

The researchers accounted for risk factors, including age, obesity, sex, underlying diseases, smoking and the severity of COVID-19 at the start of treatment. Among people taking hydroxychloroquine alone, 18 percent died; 16.4 percent of those taking chloroquine alone died; and combining either drug with a macrolide was associated with even higher numbers of deaths. In comparison, only 9.3 percent of people taking neither drug died. The drugs were also associated with heart rhythm irregularities.

But safety concerns about hydroxychloroquine have mainly come from use of the drug in people who are sick in the hospital with COVID-19, says Susanna Naggie, an infectious disease doctor at Duke University School of Medicine. She is leading a clinical trial testing hydroxychloroquine as a prophylactic to protect healthcare workers exposed to COVID-19 patients. Because of reports of harm in very sick COVID-19 patients, “people have kind of forgotten about the decades of safety data that we do have in an ambulatory, healthy population,” she says.



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