Three promising treatments for COVID-19: not a cure, but progress

We still don't have a cure, but each of these treatments could save your life.

Among the thousands of scientific studies already published about coronavirus and COVID-19, a few rays of hope have appeared. We don't have a cure yet, but at least three treatments seem to slow the virus down and save some people from the worst effects. Until we get a vaccine, these might be the best we can hope for.

Here are the three treatments that have shown the most promise, from what I've read.

1. Dexamethasone. The latest news is about dexamethasone, a widely available steroid that has been used safely in people for many years. Just a week ago, Oxford University announced results from a large study in which they gave dexamethasone to 2104 patients and compared those patients to 4321 others who received standard care. The results were striking: dexamethasone reduced deaths by 35% in patients on ventilators, and by 20% in patients who needed supplemental oxygen. 

In the announcement from Oxford, Prof. Peter Horby, one of the lead investigators of the new study, said

"the survival benefit is clear and large in those patients who are sick enough to require oxygen... Dexamethasone is inexpensive, on the shelf, and can be used immediately to save lives worldwide."

This was the best news we've had since the pandemic started. We finally have a drug that is cheap, easy to administer, and actually reduces mortality in very sick patients. 

2. Famotidine is a common, inexpensive heartburn medicine sold over-the-counter as Pepcid AC. In a very preliminary study examining the outcome of patients who took famotidine around the time of hospital admission, released in early May, doctors at Columbia University, in collaboration with New York's Northwell Health and Cold Spring Harbor Lab, compared patients on famotidine to other patients who were all very ill. The study was small and not well-controlled, so we have to be very cautious about jumping to conclusions on this one. Nonetheless, the results were promising: the number of patients in this study who either died or needed a ventilator dropped from 22% to 10% with famotidine. 

The mechanism by which famotidine might work isn't yet understood, but at least it is plausible, as Derek Lowe explains here. Northwell Health is conducting a larger, controlled study, and we should know soon if the results hold up., and we should know soon if the results hold up.

3. Alpha blockers. I wrote about these in early April: alpha blockers are another common, widely available drug (one version is called Prazosin) that has been used safely by millions of men to treat enlarged prostates. A preliminary, retrospective study showed that alpha blockers can slow down the "cytokine storm" that many patients suffer in severe coronavirus cases. 

To be more specific, patients who were already taking alpha blockers seemed to have a 22% lower risk of dying from infections that caused acute respiratory distress (ARD). This is not COVID, but the investigators used a large database with over 13,000 patients who had ARD in the past. A group of my colleagues at Johns Hopkins Medicine, led by Maximilian Konig and Bert Vogelstein, are now conducting a clinical trial to see if alpha blockers work equally well in COVID-19 patients.

All three of these treatments seem to have something in common: they slow down the body's hyper-stimulated immune response to the virus. None of them actually kill the virus, as a true anti-viral would do, but many people who are dying are suffering from their own immune system's too-aggressive attack on the virus.

Notice that I'm not including two drugs that have received a huge amount of press lately: remdesivir and hydroxychloroquine. Remdesivir has shown some promising results, but even in the results announced by its own manufacturer, Gilead, the benefits were very modest. A study published a month ago in NEJM showed that patients on remdesivir recovered from COVID-19 four days sooner (11 days rather than 15), and had slightly lower mortality, but those results were described as preliminary. Unlike the other drugs I'm excited about, remdesivir is very new, expensive, and not widely available. 

Hydroxychloroquine, by contrast, has been a total failure, as I described just a month ago. The primary reason it has gotten so much attention was, first, that it was heavily promoted by a French scientist, Didier Raoult, based on a small, very poorly-run study that he published in March; and second, that it was latched onto and promoted by Donald Trump. Since then, several larger, much better run studies have shown either that hydroxychloroquine has no benefit or, worse, that it causes harm, in the form of heart arrhythmias, which can be fatal. 

Nonetheless, we now have 3 drugs that seem to reduce mortality in the sickest patients. If anyone I know gets sick with COVID-19, I will tell them to ask their doctors for dexamethasone, if the doctors have offered it right away.

Despite this progress, the world desperately needs a vaccine. Over 100 vaccine candidates are currently being pursued, and let's all hope that some of them succeed. It can't happen soon enough.

The Environmental Protection Agency's new rule will protect polluters, not the environment

Here's a neat political trick: if you want to introduce a new law, but you know people will hate it, give it a misleading, nice-sounding name. It's surprising how well this works. Let me explain.

The U.S. Environmental Protection Agency (EPA) was founded in 1970 under Republican President Richard Nixon, and since that time it has helped the country clean up our air, water, and soil at thousands of locations. For many years, the agency was a bipartisan success.

Now, though, the EPA is run by a former coal industry lobbyist, Andrew Wheeler, and it seems more concerned with protecting polluters than with the environment. The latest example is a newly proposed rule that will allow the EPA to ignore a vast swath of scientific research that demonstrates the harmful effects of pollution on people's health. This includes research on the damage caused by burning coal and other fossil fuels.

(I should note that this new proposal was first introduced by the previous EPA administrator, Scott Pruitt, another friend of the fossil fuel industry who sued the EPA 14 times while serving as attorney general for Oklahoma.)

If the EPA were being honest, it would call this new proposal something like "Ignoring the Science on the Harmful Effects of Pollution." Of course, Congress would never go near a proposal like that, so instead the EPA calls it "Strengthening Transparency in Regulatory Science."

Huh? How can they do that?

Well, there's nothing to prevent the EPA from calling this proposal "Motherhood and Apple Pie," but they like to pretend the title has something to do with the content of the new regulation. And it does.

Here's what the new regulations do: they will allow the EPA to ignore any science where the public doesn't have access to all of the underlying data–including private, individually identifiable health data. The EPA is pretending that this rule all about openness and transparency (who could object to that?), but actually it's not that at all. It's really about protecting the fossil fuel industry.

As The New York Times reported two years ago, 

"the proposed new policy has its roots in the fossil fuel industry’s opposition to a groundbreaking 1993 Harvard University study that definitively linked polluted air to premature deaths.... In that study, which began in the mid-1970s, scientists signed confidentiality agreements so they could track the private medical and occupational histories of more than 22,000 individuals in six cities around the country."

So apparently the fossil fuel industry thought: hmm, how do we prevent the EPA from regulating us when this high-quality study shows that pollution kills? They couldn't successfully attack the study, so they concocted the strategy of demanding all the confidential data on the participants. When they were told that the data would have to remain secret, they saw their opening: "transparency" would be their mode of attack, aided by their lobbyists Scott Pruitt and Andrew Wheeler.

The Harvard study and hundreds of others like it, which have shown time and time again that air pollution kills people, will be ignored if the proposed new EPA regulation goes into effect.

Not surprisingly, public health scientists and medical experts have spoken out strongly against the EPA's proposed new rules. The American Association for the Advancement of Science said, in a statement last month, that the rules would allow the EPA "to exclude the best available science from informing EPA regulations, making it difficult for the agency to fulfill its mission to protect environmental and human health." Writing in The Hill, biostatisticians Roger Peng (a colleague of mine) and Steve Pierson wrote that the new rule 

"weakens EPA’s scientific process and undermines its mission to protect the environment and the health of the U.S. population." 

And an environmental policy watchdog, EDGI, called it 

"a comprehensive assault on science in agency decision-making."

So that's how it's done. The EPA wants to enable more pollution for its friends in the fossil fuel industry, but they can't say that out loud. The only beneficiaries of this newly proposed rule will be industries that don't want to pay for the cost of cleaning up their pollution. Meanwhile, everyone who breathes air–which, the last time I checked, included every human being on the planet–will suffer from dirtier air, water, and soil.

But don't tell that to the EPA. They are still claiming that this is just about "transparency."

Does the human placenta have a microbiome?

A few years ago, the medical community was in a bit of a tizzy over a scientific report that the human placenta has its own microbiome–a complex mixture of bacteria that maybe, just maybe, affected the health of newborn babies.

According to the New York Times' rather breathless reporting at the time, 

"the placenta ... harbors a world of bacteria that may influence the course of pregnancy and help shape an infant’s health and the bacterial makeup of its gut."

This news was very surprising to many scientists, who had long assumed that the placenta was sterile. The 2014 study, titled "The placenta harbors a unique microbiome," found hundreds of bacterial species in the placentas of 320 women. The Times report suggested that the "wrong mix" of bacteria might cause premature births, and it further suggested that the placental microbiome might seed the intestinal microbiome that babies develop later.

Turns out it was all wrong.

Many scientists were skeptical at the time. Those of us working in the microbiome field know that bacterial contamination is everywhere, and it's all too easy to "discover" microbes that came from other sources besides the tissue you thought you were studying. My colleague Jonathan Eisen (at UC Davis) called the 2014 paper and the accompanying discussion "serious overselling of the microbiome."

One good thing about science is that it corrects itself, although sometimes it takes a while. In this case, it took about 5 years. Two studies, both published in mid-2019, looked at hundreds more samples, and carefully screened out contaminants, and found: nothing.

In the first of the newer studies, a group of scientists led by Marcus de Goffau and Gordon Smith at the Sanger Institute in the UK looked at placentas from over 500 newborns. The looked very hard for any evidence of bacteria, but–unlike the scientists in the 2014 study–they took a much more rigorous view of contamination. Like the first study, they found hundreds of species of bacteria, but unlike the first study, the recognized that all of them (with one interesting exception, likely an infection) were contamination. As they explained: 

"samples of placental tissue become contaminated during labor and delivery, even when they were dissected from within the placenta."

In the second study, published just a few weeks after the UK study, a group at Bar Ilan University in Israel looked at 28 human placentas using 5 different techniques, including the techniques from the 2014 study. They found no evidence for bacteria in any of the placentas. Their conclusion was simple and stark: 

"the fetal environment in the womb is sterile."

Unfortunately, the leader of the original study, Kjersti Aagard from Baylor College of Medicine, refuses to admit that her original results were wrong. She claimed, in an interview with The Atlantic's Ed Yong last year, that the UK group were "too strict" about removing bacteria as contaminants, and that they "are not recognizing, or are naive to, other evidence for colonization" by bacteria.

To someone who works in the field, this kind of denial is all too familiar. Microbes are invisible, which means we never actually see the contamination happening–but it does happen, all the time, and many scientific results have evaporated upon closer scrutiny. Even the most careful processing of samples cannot get rid of all the bacterial DNA, because the laboratory kits that we use for sequencing themselves have bacterial DNA in them (as has been shown in several studies). 

So no, there's no placental microbiome, and that's likely a good thing.

One final note: in just the past two months, two major studies (here and here) have appeared that each claimed to find hundreds of bacterial species associated with many types of cancer. Sound familiar? Both studies tried hard to control for contamination, and both involved a massive amount of work. Despite their efforts to exclude contamination, though, I suspect we'll eventually find that these results, which are biologically quite implausible, will evaporate. It might just take a while.