Investigators at Brigham and Women’s Hospital led the first study that offers national data on the factors that may increase the risk of complications or death in critically ill COVID-19 patients. David E. Leaf, MD, MMSc and Shruti Gupta, MD, MPH, physicians in the Brigham’s Division of Renal Medicine, led a team of more than 300 investigators from over 65 hospitals across the U.S. to examine the demographics, comorbidities, organ dysfunction, treatment and outcomes of patients with COVID-19 admitted to intensive care units (ICUs).
The Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) involved manually reviewing the charts of more than 2,000 critically ill adults with COVID-19 and extracting over 800 data points per patient. The study, published in July in JAMA Internal Medicine, found that 35 percent of critically ill COVID-19 patients died in the first 28 days after admission to the ICU.
“The U.S. is the epicenter of COVID-19, yet few national data are available on the epidemiologic factors, treatments and outcomes of critically ill patients with COVID-19 in the U.S.,” says Dr. Leaf. “Our study found that critically ill patients with COVID-19 have a greater than 1-in-3 chance of short-term death. We also found that treatment and outcomes varied considerably between hospitals, with a mortality rate more than three-fold higher in patients admitted to hospitals with fewer ICU beds.”
Thirty-Five Percent of ICU Patients Died in First 28 Days
STOP-COVID involved the Brigham and 64 other hospitals from the Northeast, South, Midwest, and West regions of the U.S., including parts of the country that were heavily affected by COVID-19. The multicenter cohort study included 2,215 adults with laboratory-confirmed COVID-19 who were admitted to ICUs between March 4 and April 4, 2020.
“What is most unique about our study is the granularity of our data,” says Dr. Gupta. “We collected more than 800 pieces of data on each COVID-19 patient, which required 1 to 2 hours of manual chart review per patient.”
Overall, 784 patients (35 percent) died within 28 days, with wide variation among hospitals. Factors independently associated with mortality included older age, male sex, higher body mass index (≥40 kg/m2), coronary artery disease, active cancer, and the presence of low oxygen levels, liver dysfunction and kidney dysfunction at the time of ICU admission.
“These risk factors associated with mortality may help patients, families and physicians make decisions about how aggressive they should be in monitoring or even in admitting patients to the ICU, particularly in hospitals where resources may be limited,” says Dr. Leaf.
Even after adjusting for a variety of risk factors, death rates varied widely across hospitals, from 6 percent to 80 percent. The death rate was strongly associated with the hospital’s number of pre-COVID ICU beds. Patients admitted to hospitals with less than 50 ICU beds had a more than three-fold higher risk of death than patients admitted to hospitals with 100 or more ICU beds.
“Unfortunately, our study wasn’t able to determine the factors that might help explain the striking differences in outcomes associated with the number of ICU beds,” says Dr. Leaf. “We can speculate that this may be due to fewer resources and expertise available at smaller hospitals, but we just don’t know for sure.”
Considerable Variation in Approaches to Treating COVID-19
The study also found that hospitals varied widely in the proportion of patients who received medications and supportive therapy for COVID-19. During the study period, hydroxychloroquine, azithromycin and anticoagulants were commonly prescribed.
Interventions such as prone positioning (flipping a patient on their belly) were also being implemented. But the proportion of patients who received these measures varied widely across hospitals. For instance, the use of prone positioning ranged from 4 percent of patients at one hospital compared to 80 percent at another.
“I was surprised by the considerable variation in COVID-19 treatments across the 65 hospitals in our study,” says Dr. Leaf. “This could be because the medical community still doesn’t have strong evidence from randomized controlled trials on how to best treat COVID-19 patients, resulting in disparate practices across hospitals.”
New Therapies to Reduce Mortality in the Critically Ill
While the Brigham-led team adjusted for many demographic and severity of illness characteristics, its estimates of differences in death rates across hospitals may have been impacted by confounders that were not measured. These include socioeconomic status of patients—a risk factor increasingly recognized as important in health outcomes for COVID-19 patients. The team’s models also don’t account for varying degrees of strain across hospitals.
In ongoing research, the investigators are leveraging their data to identify promising therapies that may reduce mortality in critically ill COVID-19 patients. They are also examining various acute organ injuries in this patient population, including acute kidney injury, blood clotting and cardiac complications, such as cardiac arrest.
“STOP-COVID confirmed that factors such as older age and morbid obesity are associated with an increased risk of death in critically ill COVID-19 patients,” says Dr. Gupta. “We also identified several novel risk factors for death, such as treatment at a hospital with fewer ICU beds. That’s one of the most intriguing findings from our work, which, along with many other questions, we will be pursuing in the future.”