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.)

How disruptive are MOOCs? Hopkins launches new genomic data science series.

If you could visit a college classroom a hundred years from now, would you expect it to look just like one of today's classrooms?

I suspect not.

Yet if you walked into almost any college classroom today, you’d see a scene right out of the 19th century: students sitting in a classroom listening to a professor talk. Perhaps the professor is using a laptop to project slides, rather than writing on a chalkboard, but other signs of the 21st century can be hard to find. 

Of course the content today is different, particularly in the sciences–no one even knew what DNA was 200 years ago–but the way we teach has barely changed in the past two centuries.

Well, it’s changing now. The advent of massive, online open courses (MOOCs) is making high-quality content available to millions of people for the first time, and much of it is free. These online courses, even in their infancy, have generated a huge response, revealing the hunger out there for learning. 

Professors too are discovering something: how rewarding it is to reach thousands of students rather than just a handful. And capturing lectures on video allows us to mix and match material, updating just the parts that need changing and re-using the good stuff with relatively little effort. 

Hopkins joined the MOOC revolution last year, with a Data Science series of courses led by Brian Caffo, Jeff Leek, and Roger Peng. This June we’re launching a new specialization on genomic data science, that five of my colleagues and I are teaching. Coursera announced our 6-course specialization just a few days ago; Jeff Leek and Roger Peng produced a teaser video that you can watch here:

The specialization will cover statistics, Python programming, the Bioconductor and Galaxy environments, and more, all designed as a gentle introduction to genomic data science for students, postdocs, or even established scientists who want to start learning the tools behind genomics and “precision medicine.” 

Most of the videos are “in the can” and we’re doing the post-production now, creating the quizzes and projects that go along with the classes. Students can sign up now, but they'll have many chances to take the series. Once it launches, the classes will run every month, forever. (Okay, maybe not forever, but for a while.)

One of the first questions people ask me about MOOCs is, how can you offer all this content for free? Isn’t this a threat to the traditional university model?

You bet it is. But it’s happening, whether universities like it or not. As with other disruptive technologies, MOOCs are likely to change dramatically over the next few years, but they aren’t going away.

We're just learning how to deliver knowledge through MOOCs and we’ll get better at it. Right now MOOCs exist in a separate world from universities, but that’s likely to change. Maybe the experiment will fail, and MOOCs will fade away. Maybe that classroom in the year 2115 will look just like my classroom today. I’m betting it won't.

“Shocking Report” on flu vaccines is neither shocking nor correct

Flu season is coming, and once again it’s time to get your flu shot (or snort, if you prefer FluMist). It’s not perfect, but the vaccine is your best protection against the influenza virus.

So I was surprised to stumble upon an article titled “Johns Hopkins Scientist Reveals Shocking Report on Flu Vaccines,” which popped up on an anti-vaccine website two weeks ago. Johns Hopkins University is my own institution, and I hadn’t heard any shocking new findings. I soon discovered that this article contained only a tiny seed of truth, surrounded by a mountain of anti-vaccine misinformation. Most of it focused on a report published in early 2013 by Peter Doshi, a former postdoctoral fellow at Hopkins.

First, as Snopes.com has already pointed out, Doshi is not a virologist or an epidemiologist, but rather an anthropologist who studies comparative effectiveness research. He never conducted influenza research at Hopkins. (He’s now an Assistant Professor at the University of Maryland’s School of Pharmacy.) Second, Doshi’s 2013 article was an opinion piece (a “feature”), not an original research article, and it did not report any new findings. Third, it is highly misleading to suggest (as the anti-vax article’s title does) that Doshi somehow represents Johns Hopkins University. At Johns Hopkins Hospital, the flu vaccine is required of all personnel who have contact with patients, as a good-practices effort to minimize the risk that a patient will catch the flu from a caregiver.

But what did Doshi’s article say? Even though it isn’t new, why are the anti-vaccine sites recycling it? His central argument is this:

“The vaccine might be less beneficial and less safe than has been claimed, and the threat of influenza appears overstated.”

Let’s look at this statement. It’s almost obviously true: one only has to find a few overstated claims about the risks of flu, which isn't hard to do. But it’s also completely consistent to state that the vaccine is enormously beneficial and that the threat of influenza is very serious. See how that works? 

Doshi uses this slight-of-hand to suggest that the vaccine may not be beneficial at all. He never says this outright—instead, he just questions, again and again, whether the precise percentages reported in published studies are accurate. For example, he makes a big deal of a CDC announcement in 2013 that the vaccine’s effectiveness was only 62%. He casts doubt with phrases like 

“the 62% reduction statistic almost certainly does not hold true for all subpopulations”

which is almost certainly true, but is meaningless from the point of view of public health. Of course the vaccine doesn’t have the same effectiveness in everyone. The point is that it works most of the time. 

Doshi cites another study that showed a clear benefit for the flu vaccine, only to cast doubt on it with this argument: 

“No evidence exists, however, to show that this reduction in risk of symptomatic influenza for a specific population—here, among healthy adults—extrapolates into any reduced risk of serious complications from influenza such as hospitalizations or death in another population.”

Again, Doshi’s argument doesn’t prove that the original study was wrong, only that it doesn’t apply to everyone. But Doshi’s motivation, as evidenced by the relentlessly negative slant of his entire article, seems to be to convince people that the flu vaccine is bad.

Not surprisingly, the anti-vaccine movement has embraced Doshi (for example, here and here). And unfortunately, he seems to have accepted their acclaim: in 2009, he spoke at an anti-vaccine conference hosted by NVIC, a notorious (and misleadingly named) anti-vaccination group.

Perhaps even more disturbing is that Doshi signed a petition arguing that the HIV virus is not the cause of AIDS, joining the ranks of HIV denialists. He signed this statement while still a graduate student, so I contacted him to ask if he still doubted the link between HIV and AIDS. I also asked him if he supports flu vaccination, if he agrees with the anti-vaccine movement's use of his statements, and if he believes the flu is a serious public health threat.

On the question of signing the HIV/AIDS petition, Doshi responded that "Seeing how my name was published and people have misconstrued this as some kind of endorsement, I have written the list owner and asked for my name to be removed." (He declined to state directly - and I gave him the chance - that he agrees that the HIV virus causes AIDS.)

As for the flu itself, Doshi says "I don’t agree with CDC’s portrayal of influenza as a major public health threat." So he and I have a serious disagreement there. I asked if he agrees with the anti-vaccinationist who are using his writings to claim that the flu vaccine is ineffective, and he replied that while "ineffective" is "too sweeping," he has found "no compelling evidence of hospitalization and mortality reduction in [the] elderly."

Doshi’s argument against the flu vaccine boils down to this: the vaccine is much less than 100% effective. This is undeniably true, and the research community makes no secret of it. In fact, many of us have repeatedly called for more research into better vaccines, in the effort to create a vaccine that is not only more effective, but that (like most other vaccines) only needs to be taken once for lifetime immunity. We’re just not there yet. Meanwhile, though, the annual flu vaccine is usually effective: a recent study showed, for example, that it reduced children’s risk of ending up in a pediatric intensive care unit by 74%.

So get your flu shot (or snort) now, before flu season hits, because it takes a couple of weeks for your body to develop immunity. By getting immunized, you’ll not only increase your chances of getting through the winter flu-free, but (because you won’t spread the flu to others) you might also save someone whose immune system would be overwhelmed by influenza. 

GMOs versus antibiotic overuse: which is the greater evil?

People who worry about eating healthy food (and who doesn't?) have recently been very worried about genetically modified organisms, or GMOs.  Meanwhile, industrial livestock producers feed enormous quantities of antibiotics to cows, chickens, and bigs, as a way to make them grow faster.  Which of these practices poses the greater risk?

This one isn't even close. The threat of GMOs pales in comparison to the overuse of antibiotics, which are creating dangerous superbugs that already kill tens of thousands of people each year.

The anti-GMO forces have been making a big push recently to add "GMO" labels to foods. This particularly campaign is based on the hard-to-disagree-with notion that more information is always good. People have a right to know what they're eating, right?

Well, sure. But how many people out there understand what genetic engineering means? How many understand that virtually all the food we eat is genetically modified - including the most wholesome organic foods? Unless you live out in the wilderness eating wild nuts and berries, you're eating plants and animals that have been genetically modified over the centuries by humans, by selecting which ones to plant and breed.  The term GMO is meant to refer to something else:  precise genetic engineering, designed to alter just one or two genes. This creates genetic changes that are far less dramatic than the ones that turned ancient maize into today's modern corn, for example.  Thus the problem with "GMO" label is that it won't inform people unless they have a solid grounding in molecular genetics.

Teosinte is un-modified corn. Not so yummy, is it?

GMO opponents claim that GMOs are bad for you.  So far at least, there's no scientific evidence for this claim.  If GMOs were so bad, people would be dropping like flies every night after dinner.

But in the world of infectious disease, a different, far more deadly scenario is unfolding. Drug-resistant bacteria are spreading fast. Scientists have been warning for years that we are blindly marching towards an era when people start to die of previously treatable bacterial infections. Antibiotics, one of the greatest technological advances in the history of civilization, are losing their effectiveness.

Last week, the Washington Post reported that "nightmare bacteria" are real and on the rise.  In the U.S. alone, over 23,000 people died last year as a result of drug-resistant bacterial infections, according to the CDC. The CDC report implicated the use of antibiotics in animals as one of the primary causes.

Also last week, the Center for a Livable Future at the Johns Hopkins School of Public Health issued a report looking at how we've responded to report 5 years ago that recommended ways "to curb the threats to human health posed by modern industrial agriculture practices." How have we done? According to Dr. Robert Lawrence, director of the Center:

"There has been an appalling lack of progress.  The failure to act by the USDA and FDA, the lack of action or concern by Congress, and continued intransigence of the animal agriculture industry have made all of our problems worse."

Can the FDA regulate antibiotics in livestock? Not really, thanks to intensive lobbying by industry. One of the authors of the Hopkins report commented that the FDA is “almost pleading with industry to make voluntary changes.”

But industry isn't going to do this on their own, and so far the government has been utterly ineffective.  The study points out that:

"Congress has killed every effort to restrict the feeding of farm animals the same antibiotics used in human medicine ...  even as antibiotics have grown less effective in treating infection."

So listen up, GMO alarmists: you're protesting the wrong thing. If you really want people to eat healthier food, start raising Cain over the use of antibiotics in livestock.  If you want labels on our food, insist on labels showing whether our food animals were raised antibiotic-free.  Stop worrying about a hypothetical fear of a few genetic changes in soybeans, and worry instead about the very real rise of superbugs.  You're right to worry about how we raise our food - you're just looking in the wrong place.