Is There Any Evidence That Hydroxychloroquine Can Prevent Covid-19?

Experts debate whether the potential risks outweigh any hypothetical benefits

A pharmacist displays a box of hydroxychloroquine tablets.
Photo: Noah Seelam/AFP/Getty Images

On Monday, President Donald Trump announced he has been taking the anti-malarial drug hydroxychloroquine as a prophylaxis against the novel coronavirus — meaning he’s taking the drug, which is under investigation as a Covid-19 treatment, to prevent getting infected. There is no evidence that Trump has been exposed to the coronavirus nor is there evidence that hydroxychloroquine can prevent infection. However, there is a line of thinking that if someone has come into contact with the virus — which is not out of the question for Trump given that several White House staffers, including his personal valet, have tested positive for it — the drug may offer some protection.

Hydroxychloroquine has been a controversial medication since the start of the pandemic. The drug has both antiviral and anti-inflammatory properties, and early studies in cells suggested it might be effective against the novel coronavirus. However, results from clinical trials of its use in people with Covid-19 have been mixed. Initial promising results later came under scrutiny, and subsequent studies have reported no benefit. Most damning was a study conducted by Veterans Affairs — which has not yet been peer-reviewed — that showed people with Covid-19 who received hydroxychloroquine actually had a higher death rate than those who did not.

Other studies have been halted after evidence emerged that the drug was causing a serious and potentially deadly cardiovascular complication called QT prolongation. The QT interval, measured using an electrocardiogram (ECG), assesses how long it takes the heart to recharge between each heartbeat. A prolonged QT interval over 500 milliseconds can cause a dangerous and sometimes fatal heart arrhythmia. Because of this risk, the U.S. Food and Drug Administration (FDA) has advised people against taking hydroxychloroquine unless they’re part of a clinical study or it’s prescribed by a doctor for malaria, lupus, or rheumatoid arthritis — other indications for the drug.

Despite these concerns and the lack of evidence for its effectiveness, at least 34 clinical trials testing hydroxychloroquine for Covid-19 are currently up and running in the United States. That includes several studies that are exploring its potential as either a preexposure or postexposure prophylaxis, primarily in health care workers who are at the highest risk of exposure.

Matthew Pullen, MD, an infectious disease specialist at the University of Minnesota who’s working on the hydroxychloroquine trials there, says that the drug may act as a prophylaxis by interfering with the virus’s ability to infect cells through the ACE2 receptor (a protein on the surface of cells). If the virus does get in, the medication could still prevent the virus from replicating, theoretically stopping the infection short. No results from the prophylaxis trials have been published yet to confirm whether the drug works as a preventive medication or not.

That’s not to say that it’s fine or even a good idea for Trump to take the drug right now — if he is indeed taking it as he says he is — or that he will be safe in the long run.

“Some of the prevailing thought is that drugs like this that affect viral replication are probably more efficacious if given when your viral load is zero or low because if you’re giving a drug to stop replication but you already have millions and millions of viral particles in your body, you’re behind,” Pullen says. “Treating earlier in the course, the thought is that it may be more beneficial. Whether it is or not, that’s why we’re doing the studies to see if that is actually the case.”

As for the cardiovascular complications, Pullen says hydroxychloroquine can cause QT prolongation, but it’s not a risk as long as the person doesn’t have a preexisting condition and isn’t taking other drugs that can also cause arrhythmias. He says the most serious complications have arisen in studies that combine hydroxychloroquine with azithromycin, an antibiotic commonly paired with the anti-malarial drug to treat Covid-19 and that can also cause QT prolongation.

“When you really get down to the details of [the FDA] report, the warning was really about taking this drug in combination with azithromycin or other QT-prolonging drugs, which a lot of people had been doing in hospitals and clinics at that point,” Pullen says. “Hydroxychloroquine alone actually hasn’t really ever been documented to do that in any degree that would make us concerned about using it alone. On average, in large studies that have looked at this, they only see QT prolongation of about 10 milliseconds, which for most people is nothing.”

Pullen adds that millions of people take hydroxychloroquine for malaria, lupus, and rheumatoid arthritis for extended amounts of time without concern. In the Minnesota clinical trials, which have enrolled nearly 3,000 people so far, there have not been any serious side effects reported, including cardiac arrhythmia, although the researchers are not conducting regular ECGs to screen for this.

But that’s not to say that it’s fine or even a good idea for Trump to take the drug right now — if he is indeed taking it as he says he is — or that he will be safe in the long run.

In one recent study of people with Covid-19 who received hydroxychloroquine alone, 19% had a QT interval of 500 milliseconds or longer, and 3% had a change of over 60 milliseconds, although the average increase was just 5.5 milliseconds. Having a longer QT interval before starting the medication or being prescribed other drugs that could also affect the heart’s rhythm was associated with a greater risk of prolongation.

Trump’s use of hydroxychloroquine also goes against the very principles of the scientific process established in the United States. The FDA specifically recommends against taking drugs that have not been proven safe or effective for use, especially if it’s not an emergency scenario.

David Boulware, MD, MPH, a professor of medicine at the University of Minnesota and the lead scientist on the clinical trials, summed up the controversy in an emailed statement to Elemental, saying, “There are no data that preexposure prophylaxis is effective to prevent coronavirus. It may be. It may not be. We do not know. The only way I would recommend taking hydroxychloroquine is within a clinical trial.”

Health and science writer • PhD in 🧠 • Words in Scientific American, STAT, The Atlantic, The Guardian • Award-winning Covid-19 coverage for Elemental

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