The pandemic continues to rage in the US, and the number of people hospitalized with Covid-19 has now surpassed its prior peaks of about 60,000 in April and July. But one trend line is mercifully falling: A much smaller proportion of these critically ill patients are dying from the disease, as compared to the spring. It would be helpful if we could say exactly why.
Here’s one thing we know: The fancy, brand-name drugs that have garnered so much attention aren’t likely to have done this on their own. It’s not clear that Gilead’s blockbuster treatment, remdesivir, lowers mortality at all. Studies of convalescent plasma have reached conflicting conclusions about whether it reduces death, and while antibody cocktails—which US President Donald Trump received and called a "cure" in October—seem to be effective in mild to moderate cases, they’re not in widespread use and can’t have been the source of the declining death rates to this point. Even the drug that seems most likely to have had a major effect, a generic steroid known as dexamethasone, cut deaths among Covid-19 patients on ventilators by only 12 percent in the largest study.
But there’s another Covid-19 treatment that has become more widespread since the spring, and which experts say could be making a decisive difference. It doesn’t get much attention these days, in part because it barely sounds like a medical procedure at all. It’s proning—the practice of flipping people over so that they are lying on their stomachs—and it’s possible, at least, that this simple maneuver has played an important role in changing the course of the pandemic.
Proning, as an emergency medical procedure, is far from new. In 1976, a community ICU nurse in central Michigan named Margaret Piehl and Robert Brown, a doctor who had served in Vietnam, co-authored a paper detailing their observations that prone positioning benefited five patients with a potentially deadly fluid build-up in the lungs known as acute respiratory distress syndrome, or ARDS for short. “It’s about as low tech as you can get,” says Brown, who first came up with the idea and is now 83 years old. He and Piehl used an electric, rotating bed mounted on hoops to flip their patients over—not that low tech, perhaps. Today, hospital workers work together to move patients in regular hospital beds first onto their sides, and then their fronts, with a rolled blanket underneath a leg and an arm to alleviate some pressure.
The method is thought to work by using gravity to pull fluids away from the back of the body, where there’s generally more lung tissue, thereby clearing up more space in the lungs for oxygen. Since the lungs of patients with severe Covid are at risk of fatal fluid buildup, nurses and doctors realized early on that the same approach might be very helpful. Proning has another benefit, too, according to Andrea Armani, an engineering professor at the University of Southern California who has written on simple innovations in the Covid-19 pandemic: For health care workers who are trying to avoid contagion, it’s safer to turn someone onto their front than it is to do an intubation, which is an invasive procedure carried out near the patient’s face.
Already in the spring, proning was being heralded as a major improvement in the standard of care. The New York Times declared there was a “Low-Tech Way to Help Some Covid Patients: Flip Them Over,” and CNN celebrated that this life-saving technique was “such a simple thing to do.” Hospitals developed “prone teams,” which continue to operate today. (Before I reached out to them, neither Piehl nor Brown had heard that proning was now being used to treat patients in this pandemic. Both were delighted to hear the news.)
“I think proning has been an important part of the treatment protocol at most sites for patients with severe ARDS for quite some time now, predating Covid-19, so I think many sites were using it early in the pandemic,” explains Carolyn Calfee, a critical care doctor at UCSF Medical Center and a respiratory disease expert. It’s not clear whether or to what extent the actual use of proning for Covid patients has increased over the last 6 months, but we do know that the National Institutes of Health was recommending, as early as April, that some patients on ventilators be placed into a prone position. By mid-June, the same guidelines for the care of critically ill Covid patients suggested the need for a formal trial of “awake prone positioning to improve oxygenation”—a plea for more data that remains on the NIH website through today.
Experts say it’s likely that the procedure has had a very significant clinical impact. “The effects of proning are often extraordinary” for improving the amount of oxygen the lungs can capture, says Eric Topol, director of the Scripps Research Translational Institute. Topol adds there is “no question” it has helped keep many patients off ventilation machines, which can have detrimental side effects. Proning should not be overlooked as a key intervention, Topol says: It may well have been more transformative of patient care than remdesivir, blood thinners, dexamethasone, or any other drug to date.
Yet there’s little data to go by in assessing the exact magnitude of this transformation. The procedure does seem to elevate levels of much-needed oxygen in the blood of Covid-19 patients, but mortality rates are what matter most. A July paper from scientists in China reported that among non-intubated Covid-19 patients, the 90-day survival of those who were placed in the prone position early on was 57 percent compared with 24 percent for those who were not. That’s about triple the mortality benefit offered by dexamethasone, according to the large-scale RECOVERY trial. But the Chinese study may have methodological flaws. Aline Almeida Gulart, a physiotherapist at the Cardiology Institute of Santa Catarina, and a colleague noted in a correspondence to the same journal that many of the patients in the Chinese study who were not put in the prone position also did not receive mechanical ventilation (which is not always associated with intubation). Could this perhaps explain the vast difference in mortality rates? It’s an open question.
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On the flipside, both Calfee and Gulart say that proning might obscure the need for intubation. “This is one of the most worrying negative effects of the prone position in non-intubated patients: the false feeling that the patient is not worsening [and therefore] delaying the decision to intubate,” Gulart says. Calfee notes that among patients with ARDS, delayed intubation has been associated with an increased risk of death. (The current NIH guidelines specifically recommend against proning as an alternative therapy for patients “who otherwise require intubation.”) Calfee is also less sanguine than others that proning is a leading cause for declining death rates in this pandemic: “I think it is unlikely to be the main driving factor,” she says.
There are bigger clinical trials of proning underway, but it’s a shame that more information hasn’t emerged already this far in to the pandemic. “Randomized clinical trials of proning are ethical and useful, in part because the evidence for its benefit is largely anecdotal,” says Henry I. Miller, a senior fellow at the Pacific Research Institute, a free-market think tank, and the founding director of the US Food and Drug Administration’s Office of Biotechnology Products. “There is a need to obtain real data on the risks versus the benefits of the procedure.”
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As Miller has noted in the past, low-tech interventions often get overlooked. He points to examples such as cheap water filters and salt-rehydration tablets for diarrhea, both of which have saved lives worldwide. Lisa Gualtieri, a Tufts University School of Medicine professor who studies the intersection of technology and health, explains that basic, common-sense measures like getting sufficient sleep are unlikely to get studied as anti-Covid-19 measures to the same extent as medications. The cynical but likely reason is that mundane and low-tech interventions aren’t as profitable as new pharmaceutical drugs, so there’s less of a business incentive to document their benefit. (Last week did bring the welcome news that plain old drugstore-grade aspirin will now be included in the world’s largest clinical trial involving Covid patients.)
In the end, it may turn out that the decline in Covid death rates has little to do with proning, or with any other hospital intervention. Instead, the shift could have resulted from the changing demographics of who’s been getting sick: We know, for example, that the proportion of hospitalized patients who are over 65, and presumably at greatest risk of dying, has declined since April. It’s also possible that the mere act of maintaining physical distance or wearing a mask has reduced people’s exposure to the virus, such that when they do get infected it’s with a smaller, less deadly dose of germs. Sarah Zhang, writing in The Atlantic, notes that doctors have become more adept at tailoring treatments to individual Covid-19 patients. There’s even the remote chance that mutations that have arisen in SARS-CoV-2 could have tipped it toward being less virulent—although this is unlikely and undemonstrated.
But the lack of data on the effects of proning is especially tragic given that this is a global pandemic in need of cheap, widely adoptable measures that can reach far-flung hospitals around the world. We should have a better grasp, by now, of the extent to which the widespread use of proning explains the drop in death rates—and, much more importantly, we should have a stronger sense of whether proning does more harm than good in certain situations. There are a lot of unknowns with regards to this disease. The efficacy of one of the simplest innovations in modern medicine should not be one of them.
Updated, 11/12/2020, 12:40 pm EST:
An earlier version of this story incorrectly stated that proning was developed in southeastern (instead of central) Michigan.