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As the new chair of the Asia-Pacific Chapter of the Extracorporeal Life Support Organization (ELSO), John Fraser, MBChB, PhD, began talking with the group’s members last November about why influenza affects some people worse than others, so much so that they require extracorporeal membrane oxygenation (ECMO). Maybe 10 people, representing a minority of the chapter’s 46 member institutions, said they were interested in exploring that question, Fraser recalled a few months later.
Then, in early January, an ELSO member from China mentioned that “this thing’s happening in Wuhan,” said Fraser, an intensivist and anesthesiologist at the University of Queensland in Brisbane, Australia. “’Let’s have a look-and-see, a nice little study,’ is what I said,” he recalled. “Shows how stupid I am.”
More like how prescient he was. Over a weekend in January, Fraser and some fellow ELSO members wrote the protocol for a database to collect information about “this thing” in Wuhan, which quickly became a thing in South Korea as well.
They called their study ECMOCARD, short for Extracorporeal Membrane Oxygenation for novel Coronavirus Acute Respiratory Disease. But as the disease spread far beyond China and South Korea, Fraser and his colleagues recognized that only a small percentage of affected patients were being placed on ECMO. So the researchers expanded their focus to all patients with coronavirus disease 2019 (COVID-19) who were on a ventilator.
“Now what we’re doing is collecting all of the data from the time they get intubated and seeing how the disease progresses based upon how people manage it,” Mark Ogino, MD, international president of ELSO and a member of the study’s steering committee, said in an interview. “This is true science to me. That’s why I get excited.…I always tell my residents, ‘Don’t get trapped looking at a problem one way because that’s where you’re really going to screw up.’”
It didn’t take long to realize that this thing in Wuhan bore little resemblance to pneumonia or influenza among intubated patients.
“The lungs were totally different from patients with pneumonia, totally different from patients with flu,” Fraser said in an interview. While the lungs were typically stiff in patients with pneumonia or influenza, they were soft in patients with COVID-19.
“Bit by bit, it became clear: There was really no one who knew what to do,” Fraser said.
Growing a Study
By the beginning of May, Fraser’s brainchild encompassed more than 310 sites in 47 countries. At that time, more than a third of the sites were in the US, including the University of Pennsylvania, the Cleveland Clinic, and the Mayo Clinic, Fraser said. Data from approximately 600 patients had been entered into the study’s database, and information on about 3000 more had been collected but not yet entered as numerous sites awaited the go-ahead from their institutional review boards, he said. To reflect that it’s no longer limited to patients on ECMO, the study has been rechristened the COVID-19 Critical Care Consortium Incorporating ECMOCARD, or CCCC for short. Its goal is to sign up as many centers and include as many patients as possible.
Fraser is the first to admit that infectious disease “is definitely not [his] area” and good-naturedly calls his leadership of an international effort to study COVID-19 “a total mistake.” His background is in medical device technologies, and he’s been involved in the development of a total artificial heart called the Bivacor. He founded and leads the Critical Care Research Group, whose aim is to develop technologies to improve critically ill patients’ outcomes, at Brisbane’s Prince Charles Hospital.
His previous life as a professional actor—in his 20s, he performed with the likes of Daniel Craig and Helen Mirren—has served him well in rousing the troops to fulfill his vision of an unprecedented international collaboration. He’s enlisted rugby stars to promote the study, and he dreams of persuading former President Barack Obama, whom he much admires, to provide a few encouraging words during one of the twice-weekly CCCC Zoom meetings.
One site that probably won’t contribute nearly as much data as others is his own hospital, Fraser said. As April turned into May, he said, his intensive care unit (ICU) had but a single patient with COVID-19.
“Thank God, we’ve been fortunate enough to not be smashed,” Fraser said, referring to Australia’s low number of COVID-19 cases (as of April 28, Australia had 6725 cases and 84 deaths, according to the World Health Organization).
Fraser acknowledged that some might wonder why an Australian physician who hasn’t seen much COVID-19 would want to undertake a massive study of the disease, but, he noted, he has more time to deal with its administration than colleagues in hard-hit countries such as the US.
“If you ask me, this is the type of project that should exist: a global thing, where it’s not US vs the rest of the world,” said CCCC steering committee member Heidi Dalton, MD, medical director of adult and pediatric extracorporeal life support at the Inova Fairfax Hospital and Inova Children’s Hospital in Virginia. “As far as I’m concerned, everybody should be working with John Fraser.”
The Numbers Game
The breadth of information the CCCC wants to collect is vast, although it is already being recorded as part of routine clinical care for ICU patients with COVID-19. The study’s case report form is composed of 306 data fields, of which 116 must be completed daily.
“Because this is a new disease…with unknown pathophysiology, we don’t really know where to focus,” explained Ogino, a neonatologist at Nemours/Alfred I. DuPont Hospital for Children in Wilmington, Delaware.
“The lungs were the easiest thing to see,” he said. “But now we’ve learned it’s a systemic disease. It’s not just hitting the lungs. We know it’s impacting coagulation.” For example, Ogino said, among all patients on ECMO, those with COVID-19 develop clots more easily.
To collect and manage the data needed to dissect COVID-19, the CCCC has enlisted the help of Amazon on the front end and IBM on the back end.
“We’ve reeducated Alexa,” Amazon’s cloud-based voice service, Fraser said. “The beauty here is we’ve used a well-accepted technology and just upscaled it dramatically.”
The modification will drop the time needed to enter a single patient’s information into the CCCC database from many hours by hand to just minutes by voice, Fraser said.
Amazon is beta testing the upscaled Alexa at CCCC sites scattered around the world—in Australia, Texas, and Vietnam, to name a few—to make sure it can interface with a variety of accents, including Fraser’s Scottish brogue.
On the back end, IBM is crunching the numbers and summarizing them on a password-protected dashboard. The dashboard includes information about signs and symptoms on admission, such as heart rate and blood pressure; patient demographics, namely sex, age, ethnicity, and whether they’re a health care worker; comorbidities, such as hypertension, obesity, and smoking; treatments ranging from antibiotics and antivirals to prone positioning and nitric oxide; and complications, such as acute kidney failure and anemia.
“People are trying things [interventions] out of the box because of the relatively high mortality rate,” Dalton said. “There are lots of early suggestions of how to treat COVID-19 patients with small numbers that have already been shown to be false, now that larger patient population data are becoming available. The only way we’re going to get some answers…is with these big databases.”
Fraser predicts that once the COVID-19 pandemic has ended, the tools developed to study it will be part of its legacy.
“Out of a crisis, something good comes,” he said. “I don’t really see clinical research going back to the way it was done before.”
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Rubin R. Global Effort to Collect Data on Ventilated Patients With COVID-19. JAMA. Published online May 13, 2020. doi:10.1001/jama.2020.8341
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