Dr. Adarsh Bhimraj was feeling "helpless" in April about his ability to treat the dozens of Covid-19 patients admitted everyday to the Cleveland Clinic in Ohio.
In those early weeks of the outbreak, Bhimraj and his colleagues struggled to understand why some patients died and others recovered. It happened quickly, he said, adding that the disease could turn in a moment, sending a patient unexpectedly to the intensive care unit, where some died in days.
"As physicians, we always see death. That's part of our training, but what was different now was that we were dealing with a new disease," he said. "There were patients who were dying. We felt — I hate to use the word — helpless."
Within a few weeks, things began to change, Bhimraj said. Doctors made advances in catching the early warning signs of a severe case of the disease and learned how to intervene early and effectively. Bhimraj said he and his colleagues, as well as the patients themselves and their family members, began to feel more in control of the illness by the beginning of May.
"I hate to say it, the sacrifices the initial patients did ... they taught us," he said, adding that doctors learned anecdotally through each patient and eventually data was published defining standard care.
'Evolution of evidence'
Almost nine months into the pandemic and with more than 1 million lives lost, doctors across the world are still learning about and adapting to the virus as they discover new and horrible ways it affects the body — as well as which treatments are most effective at keeping people alive.
The percentage of people diagnosed with Covid-19 who are dying is slowly dropping, Dr. Mike Ryan, executive director of the World Health Organization's health emergencies program, said Friday.
"We're seeing clinical case-fatality rates slowly drop," he said at a news briefing. "We're seeing doctors and nurses making better use of oxygen, better use of intensive care, better use of dexamethasone."
Bhimraj, an infectious diseases specialist, leads the team charged with updating the Infectious Diseases Society of America's Covid-19 treatment guidelines for physicians. He has watched as studies and data, some promising and others too thin to be certain about, have poured in from around the world and weighed the pros and cons of each treatment possibility to determine what will maximize the chance of survival.
"Six or seven months doesn't seem like a long time, but it feels like a lifetime for us. We have seen the evolution of evidence," Bhimraj said. "I have never seen so much money, resources and people being pumped into studying a disease. The world has come together in a phenomenally remarkable way. It's unprecedented. I've not seen it in my lifetime."
Covid-19 is still killing almost 5,000 people around the world every day, including more than 750 in the U.S. But several factors have combined to drive down the rate at which Covid-19 patients appear to be dying, Bhimraj said. The U.S. is testing more people, including younger people who are less likely to become severely sick as well as people with mild or no symptoms. Those who are most vulnerable to the virus, such as the elderly and those with underlying conditions such as diabetes and heart disease are likely taking greater precautions to avoid exposure to the virus.
Physicians who spoke with CNBC said they are also increasingly confident that new treatments, clinical strategies and even lessons learned about patient care by hospital administrators have helped reduce the risk of death from Covid-19.
'Saving lives'
In the nine months since the coronavirus emerged in Wuhan, China, scientists have published at least 23,600 papers related to the virus, according to one paper published last month in the research journal Scientometrics. However, the world has failed to coordinate studies to test drugs in large randomized controlled trials, the gold standard of medical studies, said Dr. Martin Landray, a professor of medicine and epidemiology at the University of Oxford.
Landray co-leads the United Kingdom's Recovery trial, which has thousands of participants in five ongoing trials that seek to determine whether five different drugs can benefit Covid-19 patients.
In June, it found the first major "breakthrough" in treating Covid-19, finding that dexamethasone, a cheap and widely available corticosteroid, cut the risk of death by about a third among the most severely ill Covid-19 patients. His team focuses on conducting rigorously designed large, randomized controlled trials, the gold standard of medical research. He said in a phone interview with CNBC that such trials "tell you what actually works and not what you hope works."
Landray's team in the U.K. and other researchers who have conducted adequate studies have made a number of substantial findings. Remdesivir, the antiviral drug from Gilead, hastens recovery in hospitalized patients, Landray said, "but then there's a bunch of questions beyond that" about whether the drug actually prevents death caused by Covid-19. He added that dexamethasone and other corticosteroids "definitely save lives" among the most severely sick Covid-19 patients.
In the beginning of the outbreak, doctors in France reported anecdotal evidence that antimalaria drug hydroxychloroquine appeared to save lives. President Donald Trump publicly pressured the FDA to approve the drug's use on an emergency basis. Prescriptions for the 60-year-old medication surged 2,000% in March, but later studies found that it was actually hastening death in some patients and the FDA pulled its emergency authorization in June.
Another potential treatment that inspired early hope and was widely prescribed, HIV drugs lopinavir and ritonavir as a combined treatment, for hospitalized Covid-19 patients was found to "produce little or no reduction in the mortality," according to the World Health Organization.
Knowing what doesn't work, Landray said, is as significant as knowing what does work because it allows researchers to focus resources.
"There's no point just throwing these drugs at people. You've got to know if they work or not," he said, adding that there's "opportunity today as there is every day" for other researchers to conduct collaborative, large and rigorous trials.
In early September, Landray's team at the Recovery trial announced they would investigate Regeneron's antiviral Covid-19 antibody cocktail. He said it's a promising treatment but added that no conclusions will be made until the end of the study, which could come around December or January.
"In 100 days, the Recovery trial produced three results which completely changed practice internationally," he said of his team's earlier findings. "So when you get these trials right and you get compelling answers, you change the way people are treated, and they get effective drugs, and you do save lives."
'Less is more'
When it comes to the use of drugs, Bhimraj, of the Cleveland Clinic, said he's learned to take a more conservative approach. He said there's a tendency among many doctors to overuse drugs to treat symptoms, but those drugs can bring their own harmful effects.
"We always concentrate on what we can do, as clinicians. You always feel that the more stressed you are, the more you don't know about a disease, the more you do. And we think it's better. But sometimes doing less is more," he said. "If you have moderate to mild disease, the majority of people get better by themselves."
One of the most important advances doctors have made, he added, is a better understanding of how to provide critically ill patients with supplemental oxygen without putting them on a ventilator. Early in the outbreak, doctors quickly put severely sick patients on mechanical ventilators, an invasive but effective way to provide oxygen when lungs fail. The race to acquire ventilators, which were scarcely available, led the U.S. government to spend hundreds of millions of dollars to persuade companies such as Ford and GE to retool factories to build the lifesaving machines.
But over time, Bhimraj said, doctors experimented with avoiding mechanical ventilation and instead turned toward less invasive means of supplemental oxygen, which have proven successful. For patients who are struggling to breathe, doctors are increasingly instructing them to rest in the prone position, on their bellies, to help them avoid the need for mechanical ventilation.
"In April, all of us were dealing with a new disease. We didn't know what we were doing. And I hate to say it, I think we kind of overdid things," he said. "A lot of patients with more conservative care are actually getting better."
Decrowding hospitals
Beyond the decisions that doctors make, the state of the hospitals those doctors work in also largely affects the risk of dying for Covid-19 patients, according to Carri Chan, a professor at Columbia University Business School who specializes in hospital operations management. When hospitals are "congested" with patients, she said, it might take longer for doctors to notice if a patient's condition is worsening and to provide timely care.
While new cases of the coronavirus remain at a high baseline of nearly 40,000 new cases per day in the U.S., Chan said those cases are distributed across hospitals all over the nation. That stands in contrast to the situation in March, when New York City hospitals were so overwhelmed that patients were sometimes left in hallways.
"We're certainly not under the same strain as the tri-state area was back in the spring," she said, adding that if the approaching flu season turns out to be a bad one, hospitals could again be overwhelmed, when flu and Covid-19 patients overlap.
"If we do have a really bad flu season, under normal circumstances that strains the hospitals' capacity, and then put on a global pandemic that is still ongoing, that's really one of the biggest challenges that hospitals are facing right now and are trying to prepare for," she said.
Burnout
As the pandemic rages on with no end in sight, Dr. Lewis Kaplan, president of the Society of Critical Care Medicine and a surgeon at the hospital of the University of Pennsylvania, said he's increasingly concerned about burnout among health providers. At the peak of the outbreak in many regions, health workers who typically work in other parts of the hospital were moved to the ICU, he said, adding that time in the ICU can take a toll on anybody.
"There is a non-zero risk of people that are absolutely essential for the delivery of care to say, 'Is this what I want to do anymore?'" Kaplan said. "Especially the seasoned critical-care nurse who works in the emergency department or the ICU. We're worried about them."
In Europe, many health workers were encouraged to go on vacation after the spring peak of the outbreak, he said, but in the U.S., hospitals were eager to resume elective surgeries, a primary source of revenue for hospital systems. So, many health-care providers in the U.S. haven't taken a substantial break since the coronavirus emerged, Kaplan said.
If the U.S. and other countries begin to lose health-care providers now, Kaplan said, it could have devastating consequences. Advances in medicine and better treatment strategies, he said, are only helpful if trained personnel are there to administer them.
"You look at all the intensiveness of work during the pandemic," he said. "That's an awful lot of work with an awful lot of risk."
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September 29, 2020 at 11:00PM
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