Hydroxychloroquine can’t stop COVID-19. It’s time to move on, scientists say

As a frontline doctor working with COVID-19 patients at Columbia University Medical Center in New York City, Neil Schluger had horrific days.

“I would come into the ward in the morning to make rounds and say to the intern, ‘How did we do last night?’ And the intern said, ‘Well, I had 10 COVID admissions, and three of them have already died.’ It was like nothing I’ve experienced in 35 years of being a physician,” Schluger says.

When he first heard about hydroxychloroquine, he hoped it would work for his patients. He and colleagues prescribed the antimalarial drug for 811 of the 1,446 patients hospitalized at the medical center from March 7 to April 8. But the drug didn’t seem to help, Schluger and colleagues reported May 17 in the New England Journal of Medicine.

As a result, “we stopped giving hydroxychloroquine sometime in April,” he says.

And yet the numbers of cases and deaths from COVID-19 in New York City have continued to fall. “If we’d taken away a lifesaving drug, you wouldn’t expect that to happen,” he says. Instead, Schluger, now a pulmonary critical care doctor and clinical epidemiologist at New York Medical College and Westchester Medical Center in Valhalla, credits old-fashioned public health measures — mask-wearing, staying home, and social distancing — for New York’s success against the virus.

Hydroxychloroquine has been tested more than any other potential COVID-19 drug but has repeatedly fallen short of expectations. Although study after study has demonstrated no benefit of hydroxychloroquine for treating people with serious coronavirus infections, some people, including President Donald Trump, still insist the drug has merit. A viral video released July 27 that made the misleading assertion that hydroxychloroquine is an effective treatment for COVID-19 spread like wildfire online.

But the overwhelming majority of scientific evidence doesn’t support that claim. It’s time to move on from hydroxychloroquine to test other drugs that may have more promise against COVID-19, Schluger and other experts say.

Wrong cells

Initial hope that hydroxychloroquine was useful in fighting the coronavirus stemmed from lab tests showing that the drug inhibits the virus’s growth in kidney cells from monkeys by blocking its entry. But it turns out that the virus doesn’t enter human lung cells in the same way.

In those initial experiments, researchers tested the drug using African green monkeys’ kidney cells, known as Vero cells. Those cells are useful for virologists because they allow growth of a wide variety of viruses, says Stefan Pöhlmann, a virologist at the German Primate Center in Göttingen. But the way SARS-CoV-2, the coronavirus that causes COVID-19, infects monkey kidney cells is different from the way it infects human lung cells, Pöhlmann and colleagues report July 22 in Nature.

To infect different types of cells, the coronavirus has at least two major possible routes of entry. In one, the virus’s spike protein (the knobby structures on its surface) attaches to ACE2 protein on the cell membrane, and then an enzyme called TMPRSS2 cuts the spike protein. That process allows the virus to inject its genetic material into the cell, where more copies of the virus are produced.


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