Research Suggests Dexamethasone Could Benefit Patients Hospitalized with COVID-19

Early administration of dexamethasone in patients hospitalized with COVID-19 was found to reduce a composite outcome of in-hospital mortality or discharge to hospice for patients receiving supplemental oxygen, mechanical ventilation, or extracorporeal membrane oxygenation.

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Despite ongoing research efforts and thousands of trials exploring novel and repurposed drugs, few effective therapeutics are available for patients hospitalized with COVID-19. Current guidelines from the National Institutes of Health recommend systemic corticosteroids and the cornerstone of therapy in patients hospitalized with COVID-19 who require supplemental oxygen, largely based on the RECOVERY trial.

In the RECOVERY study, administration of 6 mg dexamethasone daily for up to 10 days was associated with a reduction in 28-day mortality in patients receiving oxygen only or mechanical ventilation. Although the RECOVERY platform had a large sample size and helped inform clinical management of COVID-19, the trial was notably an open-label study with no placebo group and no defined standard of care at the time.

Several other smaller clinical trials with dexamethasone and other systemic corticosteroids did find a benefit but reported different effect sizes. Because of this, the authors of the current study aimed to conduct a large, national, multicenter cohort analysis to examine and detail the clinical use of dexamethasone in hospitalized patients with COVID-19 and to explore the propensity-adjusted association with in-hospital outcomes.

Study data were compiled by the COVID-19 Consortium of HCA Healthcare and Academic for Research Generation, including electronic health records for patients hospitalized with laboratory-confirmed SARS-CoV-2 infection between July 1, 2020, and October 31, 2021, at 156 facilities in the United States. Adult patients aged 18 years and older were selected if they were hospitalized and alive for at least 48 hours with a diagnosis code for COVID-19 as well as respiratory illness during the same encounter.

After applying inclusion and exclusion criteria, 80,699 patients were included with a median age of 64 years. They were divided into 4 cohorts, with 13,040 (16.2%) requiring no supplemental oxygen or respiratory support; 56,368 (69.8%) requiring supplemental oxygen; 7618 (9.4%) requiring nasal intermittent positive pressure ventilation (NIPPV); and 3673 (4.6%) requiring mechanical ventilation or extracorporeal membrane oxygenation (ECMO).

After overlap weighting, investigators found that all-cause inpatient mortality or discharge to hospice was lower for patients who received dexamethasone within 48 hours of either admission or escalation in oxygen support in the supplemental oxygen group, and in the mechanical ventilation or ECMO group. In contrast, all-cause inpatient mortality or discharge to hospice was not lower for patients who received dexamethasone in the no supplemental oxygen group and in the NIPPV group.

In a subgroup analysis among patients receiving supplemental oxygen, improvement in the primary outcome was seen in patients older than 70 years, White patients, non-Hispanic patients, patients with diabetes, those who did not receive remdesivir, patients with a higher Charlson Comorbidity Index (CCI) score, and patients receiving low-flow supplemental oxygen. Among patients requiring NIPPV, improvement in the primary outcome was seen in White patients and those with higher CCI scores.

Finally, among patients requiring mechanical ventilation and/or ECMO, improvement in the primary outcome was seen in younger patients, non-Hispanic patients, and those who received remdesivir.

Based on these findings, the investigators concluded that early administration of dexamethasone was associated with improved mortality or discharge to hospice in patients requiring supplemental oxygen or mechanical ventilation and/or ECMO. Future research should continue exploring patient subgroups to help inform and individualize COVID-19 therapy.

REFERENCE

Mourad A, Thibault D, Holland TL, Yang S, et al. Dexamethasone for Inpatients With COVID-19 in a National Cohort. JAMA Netw Open 2023;6(4):e238516. doi:10.1001/jamanetworkopen.2023.8516