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.)

No, megadoses of vitamin C won't cure a coronavirus infection

The world is awash in treatments for COVID-19, the illness caused by coronavirus. Or at least that's what you might think if you just searched the internet.

The truth is, we don't yet have any effective treatments for COVID-19, although thousands of scientists are working furiously to try to create them.

Today we'll look at just one of the supposed treatments, which is being actively promoted on social media and many websites: vitamin C.

For those who don't want to read further, I'll start with the conclusion: vitamin C won't help to prevent or to treat coronavirus infection. I wish we had such a simple solution, but we don't.

Now let's back up a bit. Why would anyone think that vitamin C might be effective in treating this terrible virus? Vitamin C is an essential nutrient, and we all need it, but most people get plenty of vitamin C in their normal diet. As I've written before, taking vitamin C supplements is unnecessary but probably harmless, although megadoses carry the risk of kidney stones.

The modern craze with vitamin C started with Linus Pauling, a brilliant chemist and a Nobel Prize winner. Late in his career, he wrote a book promoting vitamin C as a miracle cure for many illnesses, including the common cold (which is caused by a virus). He had very little good evidence for this belief, but his promotion of vitamin C led to hundreds of studies testing his hypothesis. The bottom line: vitamin C doesn't work at preventing or curing the common cold. (See Paul Offit's book if you want more details on this and many other "miracle" cures.)

But wait, someone might object: haven't some of those vitamin C studies (as in this review paper) shown a benefit against the common cold? Well yes, but when you run hundreds of studies of a treatment that doesn't work, this is what happens: negative studies are hard to get published, but positive studies are easier. Run enough studies, and a few of them, merely by chance, will show a small positive effect. That's what we've seen with vitamin C.

Today, though, everyone is looking for a cure for COVID-19, and not surprisingly, many people (even some doctors) are claiming vitamin C is the answer. I've seen Twitter users explain, very confidently, that you just need to take 12,000 mg of vitamin C and you'll get better. This website comes right out and states that high-dose vitamin C will cure coronavirus, based on a widely-shared video from a doctor in China. (I won't provide the link because it has already done enough damage.)

It's almost impossible to disprove a claim that a treatment works. For example, I could claim that ginger snap cookies helps to prevent coronavirus infection. That's right! Ginger snaps, made with real ginger, which seems to have magical curative properties. If you object, I could demand that you prove me wrong–but the onus is on me, as the one making the claim, to first provide some genuine evidence. We haven't seen anything like that for vitamin C.

We need well-controlled experiments to know with any confidence that a treatment works. Some doctors at Wuhan University have started a trial of vitamin C to see if it has any benefits for COVID-19, but results won't be available for many months. I'm skeptical, but at least they're approaching the question the right way.

Dozens of studies of new treatments for COVID19 are being launched right now, with remarkable speed due to the urgency of the pandemic.The WHO has just launched trials of the 4 most promising existing drugs (which don't include vitamin C, I should add). To obtain a believable, positive result, we need to see evidence that a carefully administered treatment provides a significant benefit over what we're doing now–which is little more than supportive care, unfortunately.

Meanwhile, we'll have to wait and hope that one of the plausible efforts currently under way will yield an effective treatment. We've been down this road too many times with vitamin C, though, and the chances that it will have any effect are, based on past experience, close to zero.

Got cold. Try zinc?

Having a cold is no fun.  Sore throat, runny nose, general feeling of all-around blechiness.  About the only good thing I can say about colds is that they don't last long, usually about a week.

We still don't have a cure for the common cold, but it's not for lack of trying.  For decades, Nobel laureate Linus Pauling promoted mega-doses of vitamin C as a way to prevent colds, but he turned out to be wrong on that one.  Somewhere in the neighborhood of 200 different viruses cause us to get colds, and we don't seem to be able to get rid of any of them.

In recent years, the most popular new remedy is zinc, usually in the form of a lozenge.  The evidence for zinc's effectiveness is not entirely clear, but a review published just last month, which looked at 13 different studies, concluded that zinc seems to help, just a little bit.  All 13 studies were randomized controlled trials, the gold standard of research, and collectively they included 966 people.

That sounds encouraging, but the benefit was disappointingly small: zinc seemed to shorten the duration of a cold by about one day.  So instead of being sick for 7 days, you might be sick for 6 days.

Or maybe not: Dr. Terence Davidson from UC San Diego argues that if you look at just the more rigorous studies, the effect vanishes entirely.

Chunks of elemental zinc

Then there are the worrisome reports that Zicam, a zinc-based cold remedy, causes people to lose their sense of smell.  (This may not sound so terrible, but some people reported a permanent loss.  Imagine never being able to smell fresh-baked bread again.)  In 2009, these reports led the FDA to issue a warning advising consumers to stop using three particular Zicam products.  In addition to over 130 reports directly to the FDA, Zicam's manufacturer had over 800 additional complaints about loss of sense of smell.

In an ironic twist, Zicam markets its products as homeopathic remedies, which means that the FDA cannot regulate them. It also means that they shouldn't contain any active ingredients, because homeopathic preparations are diluted until they contain nothing at all.  But Zicam does contain zinc, quite a lot of it, and the FDA's warning letter demanded that Zicam stop marketing these products because they had never demonstrated that they were safe and effective.

Zicam markets a wide range of zinc-containing products, and the FDA's warning only affected three of them.  Zicam's website today states that "there is no valid, scientific evidence showing a link between Zicam and anosmia [loss of sense of smell]."  Strictly speaking, this is correct, but there have been published reports suggesting a link, such as this one from 2006 and this one from 2009.  These studies looked at nasal sprays, not lozenges, suggesting that the risk (if any) comes from spraying the zinc product directly up your nose.

Aside: Zicam also claims that their products cure allergies too, for which there is not a shred of evidence.  Their website makes the sweeping claim that "all Zicam products are both effective and safe when taken as directed." I see no reason to trust these guys.

Conclusion: I'm not taking zinc.  The side effects might be minimal, but the benefit is very small and possibly zero.  I'll stick with hot tea, which at least makes my throat feel better.  Or chicken soup.  That can cure almost anything.

A breakthrough cure for Ebola

Ebola is one of the nastiest, most frightening viruses known to man. Its victims suffer fevers, muscle weakness, and other symptoms that progress to severe bleeding, both internal and external, that eventually causes them to bleed to death. All known strains of Ebola virus have very high mortality rates, ranging from 25% to 90%, and there is no cure. Ebola virus was the subject of a dramatic and frightening 1995 disaster movie, Outbreak, starring Dustin Hoffman, Rene Russo, and Morgan Freeman.

Last week, in what may be the biggest medical breakthrough of its kind in years, a group of scientists published results in The Lancet describing a completely new type of anti-viral treatment that appears to cure Ebola. They report a 100% success rate, although admittedly the test group was very small, just 4 rhesus monkeys.

This is a breakthrough not only because it may give us a cure for an uncurable, incredibly nasty virus, but also because the same method might work for other viruses, and because we have woefully few effective antiviral treatments. We can treat bacterial infections with antibiotics, but for most viruses, we have either a vaccine or nothing. And a vaccine, wonderful as it is, doesn’t help you after you’re already infected.

The scientists, led by Thomas Geisbert at Boston University, used a relatively new genomics technique called RNA interference to defeat the virus. Here’s how it works. First, a little background: the Ebola virus is made of RNA, just like the influenza virus. And just like influenza, Ebola has very few genes - only 8. One of its genes, called L protein, is responsible for copying the virus itself. Two others, called VP24 and VP35, interfere with the human immune response, making it difficult for our immune system to defeat the virus.

Geisbert and his colleagues (including scientists from Tekmira Pharmaceuticals and USAMRIID) designed and synthesized RNA sequences that would stick to these 3 genes like glue. How did they do that? We know the Ebola genome’s sequence – it was sequenced way back in 1993. And we know that RNA sticks to itself using the same rules that DNA uses. This knowledge allowed Geisbert and colleagues to design a total of 10 pieces of RNA (called “small interfering RNA” or siRNA) that they knew would stick to the 3 Ebola genes. They also took care to make sure that their sticky RNA would not stick to any human genes, which might be harmful. They packaged these RNAs for delivery by inserting them into nanoparticles that were only 81-85 nanometers across.

In the key experiment, the scientists infected rhesus monkeys with a dose of Ebola that was 30,000 times greater than the normal fatal dose. They injected the siRNA treatments 30 minutes later, and again each day for 6 days. All the monkeys survived with no long-term effects.

When I read this story in The Lancet, my first reaction was: wow. A brand-new antiviral treatment, and against Ebola? In a commentary in The Lancet, Heinz Feldmann wrote that we are “in desperate need of approved countermeasures against Ebola-virus infections,” and called the new study a “milestone.” That’s putting it mildly.

Somehow, except for the UK Daily Mail, the major media outlets seem to have entirely missed this story, which I think is by far the biggest medical story of the week, if not the year. Ebola virus doesn’t get much attention (notwithstanding the 1995 movie about it), primarily because it occurs in central Africa. But air travel has made our world much smaller, and even a relatively isolated virus could easily get out of control.

There’s still a much work needed to turn the new Ebola treatment into an approved drug, but the prospect of a cure is suddenly very real, and the techniques used to create it are truly remarkable.