A possible treatment for COVID-19?

Amidst all of the unproven and ineffective treatments being promoted for coronavirus treatment, a new possibility has just emerged.

Scientists around the globe are devoting enormous resources to trying to develop new treatments for COVID-19, the pandemic that is sweeping across the world. So far, though, we don't have any effective therapies or vaccines.

That might be about to change. What's particularly exciting is that this new treatment uses a widely-available drug that has already been shown to be safe in humans.

In a new preprint, a team of my colleagues at Johns Hopkins University School of Medicine, led by Maximilian Konig, Bert Vogelstein, Joshua Vogelstein, Susan Athey, Shibin Zhou, and Chetan Bettegowda, describe the potential of prazosin to slow down and possibly prevent one of the worst effects of COVID-19: the cytokine storm.

[Some background: a cytokine storm is an extreme immune response of your own body. When coronavirus (SARS-CoV-2) enters the lungs, your immune system responds with virus-fighting cells that release small proteins called cytokines. In some cases, the immune system just keeps amplifying its response, sending more and more cytokines even though the infection might be under control. If it gets too bad, the cytokine storm itself may be fatal. Cytokine storms have been implicated in other viral diseases, including influenza and SARS.]

Let me start with a caveat: if prazosin works, it isn't a cure. However, it might prevent the need to go on a ventilator, which would be a huge benefit in a country (and a world) that has a severe shortage of ventilators right now. Even more important, it might save patients with severe COVID-19 from dying.

Several of the scientists involved in this new study have shown previously that drugs like prazosin (which are known technically as alpha-1AR antagonists) can prevent a cytokine storm–in mice. They realized that results in mice often fail to translate to humans, but in the current pandemic, how could they find time to do a new study?

They didn't: instead, they looked at a medical database and collected records from 13,125 men who had acute respiratory distress (ARD) from a variety of causes in the years 2007-2015. ARD is not the same as COVID-19, but it's similar; and if a cytokine storm occurs in ARD, patients are more likely to require a ventilator and/or die. Because prazosin is widely used by men (most commonly for enlarged prostates), they were able to compare the outcomes of men who had incidentally been taking prazosin to men who hadn't.

The results: men who had been taking prazosin had a 22% lower risk of either needing a ventilator or dying. That's not a huge effect, but it could be a game changer for our overwhelmed hospitals in the midst of this pandemic. Even a modest reduction in the number of patients needing ventilators–or dying–would be a huge win for public health. Also, the patients in this retrospective study weren't taking prazosin to treat their respiratory distress, and it's possible that higher doses might have a larger effect.

There are many more caveats here. First, the study I'm describing is a medRxiv preprint, meaning that it has not been peer-reviewed. In addition, the data are from a retrospective study of men who had a different disease, not COVID-19. So maybe prazosin won't work to prevent cytokine storms caused by the coronavirus.

But maybe it will. My colleagues shared their preprint with me because they are convinced that, if nothing else, their hypothesis needs to be examined by as many scientists and doctors as possible. They are starting their own clinical trial, but they hope that these preliminary findings "will inspire immediate clinical trials in countries now desperate for new ways to reduce hospital admissions, ventilator needs, sickness, and death."

Prazosin has been in medical use since 1974 and is widely available and inexpensive. It's one of the most promising treatments I've heard of, far more promising than hydroxychloroquine. Even if it only slightly reduces the need for ventilators, it may have a huge impact on this pandemic. We need to start investigating it right away.

(Note: I've made it a rule not to write columns about my own or my colleagues' scientific accomplishments. Many rules are being broken in this pandemic, and I decided the urgency of this potential treatment was more than sufficient to break my usual rule.)