As many as one-fifth of patients hospitalized with severe COVID-19 in the United States who may have benefitted from treatment with the anti-inflammatory steroid dexamethasone or closely related drugs were not given such treatment at the height of the pandemic, according to a large, nationwide study led by researchers at Johns Hopkins Bloomberg School of Public Health.
The study also found that the use of dexamethasone and another drug, the antiviral remdesivir, varied greatly across health systems in the U.S. Dexamethasone and remdesivir are among a handful of recommended treatments for patients hospitalized with COVID-19 who require oxygen.
For their study, the researchers analyzed anonymized health records of 137,870 people hospitalized in the United States with suspected or confirmed COVID-19 for the thirteen-month period from February 2020 through February 2021.
The research is published online August 16 in Annals of Internal Medicine.
“These findings underscore the wide variation in COVID-19 care across American health systems,” says study lead author Hemalkumar Mehta, PhD, assistant professor in the Department of Epidemiology at the Bloomberg School. “This variation is vital to understand, since it may indicate that many patients who would benefit from these treatments may not be receiving them.”
Dexamethasone is an inexpensive and widely available steroid drug that has been in use in the U.S. since the early 1960s, chiefly to reduce serious inflammation in severe arthritis or allergic anaphylactic shock. The drug became a standard clinical weapon against severe COVID-19 worldwide after a U.K. clinical study, whose results were announced in June 2020, found that it reduced mortality by more than one-third when given to ventilated COVID-19 patients, and by more than one-fifth when given to patients who were getting supplemental oxygen.
Remdesivir, an antiviral drug originally developed as a treatment for Hepatitis C virus infection, showed efficacy against the coronavirus that causes COVID-19 in early lab-dish tests. Later, in large clinical trials, its use significantly cut the lengths of COVID-19 patients’ hospital stays. In May 2020, remdesivir received emergency use approval in the U.S. for treating COVID-19, and in October 2020 it received full FDA approval.
To get a sense of how these drugs were put to use against COVID-19 in the U.S., the researchers analyzed data from the National COVID Cohort Collaborative (N3C), a National Institutes of Health-sponsored collection of electronic health records on millions of COVID-19 patients from 43 health systems nationwide. The study covered 137,870 adults who were hospitalized with COVID-19, and met other criteria—for instance, those hospitalized for at least one day—between February 1, 2020 and February 28, 2021.
The analysis showed that the rate of dexamethasone use in hospitalized COVID-19 patients—with or without mechanical ventilation—climbed steeply in June 2020 and continued to climb until it peaked in mid-November at just over 50 percent of patients. Usage then fell to about one-third of patients by late February 2021.
The rate of remdesivir use showed a similar pattern, peaking in November 2020 at about 35 percent. The results also showed that the rate of use of the drug hydroxychloroquine rose to about 42 percent in March 2020 but fell back to near zero the following month, after clinical trial evidence suggested that it was ineffective against COVID-19.
Dexamethasone use was higher among patients whose COVID-19 was severe enough to require mechanical ventilation to support the lungs. However, even after June 2020 when dexamethasone’s efficacy had been established, the rate of its use in ventilated patients varied widely across the 40 health systems represented by the data, with a median value of only 80 percent. The analysis revealed that the rate of remdesivir use in hospitalized COVID-19 patients also varied widely across health systems.
The findings, the researchers say, suggest the possibility that dexamethasone has been underused in patients with severe COVID-19, and more generally that clinical practice for treating COVID-19 has not developed a set of uniform standards.
In an accompanying editorial, Marshall J. Glesby, MD, PhD, and Roy M. Gulick, MD, MPH, of Weill Cornell Medicine, highlight the evolving evidence on COVID-19 treatments and its influence on treatment uptake, including considerable variation among U.S. health systems.
“The COVID-19 pandemic unleashed a wave of scientific activity to identify new or repurposed treatments to halt the disease,” says G. Caleb Alexander, MD, MS, a study author and professor in the Bloomberg School’s Department of Epidemiology. “It is vital that these treatments are used consistently across hospitals and health systems, so as to prevent as much death and disability as possible.”
The researchers note that their analysis did not take into account factors such as drug shortages and differences between COVID-19 patients receiving oxygen supplementation—differences that might help explain some of the apparent variation in treatment utilization rates.
“It’s possible that, for example, some hospitals had sicker patients on average compared to other hospitals—it will be critical to understand the potential factors in future investigations,” Mehta says.
“Use of Hydroxychloroquine, Remdesivir, and Dexamethasone Among Adults Hospitalized With COVID-19 In The United States” was co-authored by Hemalkumar Mehta, Huijun An, Kathleen Andersen, Omar Mansour, Vithal Madhira, Emaan Rashidi, Benjamin Bates, Soko Setoguchi, Corey Joseph, Paul Kocis, Richard Moffitt, Tellen Bennett, Christopher Chute, Brian Garibaldi, and G. Caleb Alexander.
Support was provided in part by the National Institute on Aging (1K01AG070329-01) and the National Heart, Lung, and Blood Institute (T32HL139426-03).
Caleb Alexander is past Chair of FDA’s Peripheral and Central Nervous System Advisory Committee; has served as a paid advisor to IQVIA; is a co-founding principal and equity holder in Monument Analytics, a health care consultancy whose clients include the life sciences industry as well as plaintiffs in opioid litigation; and is a member of OptumRx’s National P&T Committee.
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