A Blog by Jonathan Low

 

Nov 5, 2020

How A Simple Rule Is Keeping Covid Deaths Down

Given the rate at which healthcare professionals are learning about how to treat Covid, preventing infections now means the likelihood of surviving it later. JL

Sarah Zhang reports in The Atlantic:

The death rate for COVID-19 has fallen dramatically. This change cannot be explained by COVID-19 patients getting younger and healthier. Lack of knowledge about the virus constrained what doctors did. “We’re nowhere near the point where we have medical care dictated by evidence."  For now, they have experience to go on, which is better than nothing. But it’s not data. The longer we prevent infections, the better prepared to treat the people that might eventually get it. There will never be a good time to get coronavirus, but getting it later will be better than getting it today, tomorrow, next week, or next month.

During the first COVID-19 surge of the spring, the mantra was “Flatten the curve”—to buy time, using every tool available.

Seven months later, it’s possible to measure what that time has bought: The death rate for COVID-19 has fallen dramatically. Hospitals in most places are not overburdened, and treatments are improving in many small but cumulative ways. In one study of patients hospitalized in a New York City health system, the adjusted death rate fell from 25.6 percent in March, at the pandemic’s onset, to 7.6 percent in August.

This change cannot be explained by COVID-19 patients getting younger and healthier. The study’s authors adjusted the mortality rates for age and other risk factors. “People should take this as validation of all the hard work and sacrifices they have been making,” says Leora Horwitz, an internist and the study’s lead author. “It has made a difference.” Similar patterns hold throughout New York City and in the U.K., and they underscore the reason for flattening the curve. The longer we can prevent infections, the better prepared we will be to treat the people that might eventually get it.

What was true about flattening the curve in March is still true now. As the U.S. faces a third coronavirus surge, Horwitz warns that “these numbers are not static.” We are still learning about how to treat COVID-19, and truly game-changing therapies have yet to arrive. When hospitals become overburdened—as they are starting to in El Paso, Utah, Wisconsin—death rates may rise again. The axiom from the beginning of the COVID-19 pandemic still applies today. “If I have to choose to have it, probably the later, the better,” says Sanja Jelic, a pulmonologist at Columbia University Medical Center.

Jelic was among the doctors treating COVID-19 patients in New York in the spring, when hundreds of people were turning up at the city’s hospitals everyday unable to breathe. Patients were crammed into hallways; doctors were overworked. Normally, Jelic says, she might have seen eight or 10 patients in a day. In April, she and two fellows were responsible for 60, any of whom might crash and need to be intubated.

Lack of knowledge about the virus constrained what doctors did. Hospitals initially favored ventilation in part because doctors feared that high-flow therapy oxygen could aerosolize the virus and spread it to staff who didn’t have adequate supplies of personal protective equipment. (Now, of course, we know that the virus can be spread through aerosols generated from just normal talking and exhaling.) In some cases, aggressive intubation might have done more harm than good in patients who didn’t need it. Doctors stopped putting every patient on a ventilator once they realized the benefits of less invasive oxygen therapy and even turning patients onto their bellies, also known as proning.

Because COVID-19 can, like many conditions, manifest so differently from person to person, knowing which patients might benefit—or be hurt—by a treatment is a key part of the learning curve. “There isn’t a one-size-fits-all treatment,” says Nicholas Caputo, a doctor at Lincoln Hospital in the Bronx, who was one early advocate of proning. Ventilation is one example of a treatment that can help or hurt depending on the patient. Another is dexamethasone, a steroid that suppresses the immune system. The drug has been shown to reduce mortality in patients with severe COVID-19, whose immune systems have become hyperactive, but might harm patients with milder cases whose immune systems are still trying to clear the virus.

Doctors have also learned to watch out for COVID-19’s more unusual symptoms. The disease has been linked to kidney failure; those patients might need dialysis. It’s also linked to blood clots; patients who show warning signs might need blood thinners. Seeing more cases of COVID-19 has also allowed doctors to refine details like the size of tubing used with ECMO, an artificial-lung technology for the sickest patients who aren’t doing well on ventilators.

A lot of this experience has been shared in real time and informally. J. Eduardo Rame, a cardiologist at Thomas Jefferson University Hospitals, helps convene a regular Zoom forum where doctors discuss the latest, such as how to use ECMO. “Experiential learning,” as Rame puts it, has been vital for sharing information about a new disease. But doctors are also trained to rely on data and randomized, controlled trials, not anecdotes. “We’re nowhere near the inflection point where we can have medical care dictated by evidence,” Rame says, which puts doctors in a strange position. For now, they have experience to go on, which is better than nothing. But it’s not data.

Randomized, controlled trials can be difficult to run in the middle of a pandemic. Hospitals under stress might not have the time and resources. Doctors may be loath to deprive patients of an experimental drug that just might help, as is necessary for placebo-controlled trials. These trials, though, are valuable for identifying not just what works but what common experimental treatments don’t work and might even cause harm. The list of drugs that have failed in rigorous trials includes hydroxychloroquine, tocilizumab, sarilumab, interferon, and antivirals already used to treat HIV. Nearly all of the trials in this first group have involved repurposing drugs used to treat other conditions.  

Another set of clinical trials involve monoclonal antibodies, which mimic the proteins the human body naturally makes against pathogens. Monoclonal antibodies are the best near-term shot for a targeted therapy against COVID-19. President Trump gave them a huge boost of visibility after receiving Regeneron’s antibody infusion, which very early data now suggest could reduce doctor visits for COVID-19. The trials still need to run to completion though, and availability will be limited, because antibodies are particularly difficult to manufacture. Regeneron said in early October it has doses for 50,000 patients, which is fewer than the number of people getting COVID-19 each day in the U.S. right now. Antibody therapy will get better in the future too, as researchers try to engineer cheaper and more potent versions.

All of this means that COVID-19 treatments are likely to become both more effective and more accessible in the future. And eventually there will be a vaccine. At some point, COVID-19 will become a manageable disease, akin to the flu. There will never be a good time to get the coronavirus, but getting it later will almost certainly be better than getting it today, tomorrow, next week, or even next month.

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