Months of trial, error in ICUs offer clues on how to save COVID-19 patients

Dr. Sanja Jelic’s worst day in almost two decades as a critical care doctor in New York City was April 6.

Faced with an unmanageable influx of coronavirus patients at Columbia University Irving Medical Center’s step-down unit, an intermediate care ward, Jelic made an unorthodox decision: She asked those struggling to breathe to roll onto their bellies while they waited for intubation to mechanically ventilate their inflamed lungs.

It wasn’t a random guess. Laying patients in the stomach-down prone position is known to improve oxygenation in sedated, intubated patients with acute respiratory distress syndrome. But there was no guarantee the same would hold true for wakeful COVID-19 patients who were gasping for air.

“We had to buy time,” Jelic, who is also an associate professor of medicine at Columbia University, recalled in an interview. “I remember, the first three patients really had a dramatic improvement in their oxygenation.”

In the absence of a cure, doctors like Jelic were left relying in part on trial and error, but months into the most destructive pandemic in a century, their collective experience is starting to build a framework of how best to cope with coronavirus patients.

As many as 1,000 COVID-related research papers are being released daily ahead of peer review and publication, according to Soumya Swaminathan, the World Health Organization’s chief scientist. “Our goal is to see that the learnings from science are as quickly as possible channeled into impacts for patients and communities,” she told reporters in Geneva on Thursday.

The collective experience might be showing results. U.S. deaths, which often ranged between 2,000 and 3,000 a day in April and May, have mostly remained below 1,000 and in the low hundreds since the beginning of June.

The WHO is collating data from countries to identify crucial elements that reduce mortality. These include how health systems triage COVID-19 patients, how they protect those vulnerable to more serious complications, and the speed with which they provide intensive care.

The goal is to create a tool box that will enable doctors to provide better care for the full range of patients with COVID-19, which has turned out to be more than just a respiratory disease, said Sylvie Briand, the WHO’s director for global infectious hazard preparedness.

“It’s not only what you do—sometimes at this level there is no difference—but it’s how you do it,” Briand said in an interview.

Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, also credits better experience with medicines.

“Whenever you’re in an outbreak, there are two things about treatment that contribute to improvement,” he said. “Not only do you get better in practice, but you get better because of new treatments.”

In April, Gilead Sciences’s antiviral remdesivir, now approved with the brand name Veklury, was shown to speed recovery time. Last month, the inexpensive corticosteroid dexamethasone was found to reduce deaths by one-third among patients receiving mechanical ventilation. Doctors are also routinely administering heparin and other anticoagulants to prevent dangerous blood clots from forming in the veins of the critically ill.

Although the “awake proning” approach Jelic and colleagues tried hasn’t been properly studied yet in a large clinical trial, it points to a cheap and simple way overwhelmed health centers may be able to help severely ill patients. Their research, published in a June 17 letter to the Journal of the American Medical Association, indicated that it reduced the probability patients would need intubation. The journal also published an invited commentary subtitled “necessity is the mother of invention.”

“I couldn’t agree more with the title,” Jelic said. “I have never seen this much strain on our ICU resources.”

Laying on the stomach improves blood circulation in the upper portion of the lung, she said, increasing the volume of oxygen and carbon dioxide that can be exchanged. It also decreases pressure around the lung, and can help clear secretions from the airways, studies show.

While combination treatments—the HIV medications ritonavir and lopinavir, and the antimalarial drugs hydroxychloroquine and chloroquine with the antibiotic azithromycin—failed to reduce death in hospitalized COVID-19 patients, there’s optimism for others. These include antibody-based therapies and blood products from survivors.

The antiflammatory infusion infliximab, sold by Johnson & Johnson and Merck as Remicade, is being studied by Tufts Medical Center in Boston as a way of circumventing the major cause of lethal complications in a subset of COVID-19 patients: A damaging immune response, sometimes referred to as a cytokine storm, that usually occurs in the second week of illness.

Infliximab blocks tumor necrosis factor-alpha, a cell-signaling protein or “cytokine” that plays a key role in driving the immune system to exhaustion in response to infections, said Paul Mathew, a cancer specialist at Tufts University School of Medicine who’s leading the study. The medicine may also help avert life-threatening blood-clotting problems that can occur in COVID patients.

“Little by little, we discovered new signs and symptoms of the disease,” said the WHO’s Briand. “Now we know that there is really a lot of possibilities for this virus to attack the human body.”

These range from a sudden lack of smell to a multi-system inflammatory syndrome in children—features that have become more apparent with more than 11 million COVID cases worldwide. Others include clotting-related disorders that can be benign skin lesions on the feet, sometimes called “COVID toe,” or potentially lethal strokes.

The more COVID patients Jarrod Mosier sees in his hospital’s intensive care unit in Tucson, Arizona, the more he says he’s convinced that saving lives comes down to protecting the lungs of those with acute respiratory distress syndrome, or ARDS, caused by pulmonary inflammation. Most patients need breathing support, but too little or too much air pressure and volume can damage the lungs further.

“I look at all of those things and tinker with the ventilator for a good while every day to try to find that balance,” Mosier said. “To me, that is the thing that will save the most lives in this disease—just excellent critical care management of ARDS.”

Mosier said he’s hoping it results in better patient survival. “I think that’s the case, but it’s very hard to answer that question when you’re in the thick of it,” he said. “Some days I think we’re actually getting pretty good at this. And other days I think, ‘This is demoralizing.'”