By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

Dr. Deresinski reports no financial relationships relevant to this field of study.

SYNOPSIS: Dexamethasone administration is associated with reduced 28-day mortality in oxygen-requiring COVID-19 patients, including those receiving mechanical ventilation.

SOURCE: RECOVERY Collaborative Group; Horby P, Lim WS, Emberson JR, et al. Dexamethasone in hospitalized patients with Covid-19 — Preliminary report. N Engl J Med 2020; Jul 17. doi: 10.1056/NEJMoa2021436. [Online ahead of print].

As part of the RECOVERY trial designed to test multiple potential treatments for patients with COVID-19, the investigators randomized 2,104 patients to receive dexamethasone for up to 10 days in a dose of 6 mg per day, and 4,321 patients to receive usual care. Initially, hospitalized adults (including pregnant and breastfeeding patients) with proven or suspected COVID-19 were eligible. The age limitation was eventually eliminated. The mean age of the patients was 66.1 years and (strangely) only 36% were female. Fifty-six percent had a significant comorbidity: One-fourth each had diabetes mellitus or heart disease, and one-fifth had chronic lung disease. Sixteen percent were receiving mechanical ventilation or extracorporeal membrane oxygenation (ECMO) at the time of randomization, while 60% were receiving oxygen without invasive ventilation, and 24% received neither.

Dexamethasone was given for a median of seven days; 8% of usual care patients also received dexamethasone, and one-fourth of patients in each arm received azithromycin. Only a few patients received remdesivir.

At 28 days, 482 (22.9%) of the 2,104 dexamethasone recipients and 1,110 of the 4,321 (25.7%) usual care patients had died (rate ratio, 0.83; 95% confidence interval [CI], 0.75 to 0.93, P < 0.001). Among those patients receiving mechanical ventilation, 95 of 324 (29.3%) dexamethasone recipients and 283 of 2,604 usual care patients (41.4%) died by 28 days (rate ratio = 0.64; 95% CI, 0.51 to 0.81). Among those who received oxygen without invasive ventilation, 298 of 1,279 (23.3%) dexamethasone recipients and 682 of 2,604 (26.2%) usual care recipients died (rate ratio = 0.82; 95% CI, 0.72 to 0.94). In contrast, there was no significant difference in outcomes among patients who had not required oxygen therapy at randomization.

COMMENTARY

Prior to the announcement of the results of this study, the use of corticosteroids in patients with COVID-19 was discouraged, based on prior negative experiences with their use as adjunctive therapy of infections due to influenza virus, SARS-CoV, and the Middle East respiratory syndrome (MERS) virus. Immediately upon receiving these results, official organizations such as the World Health Organization, the National Institutes of Health, and the Infectious Diseases Society of America (IDSA) reversed their positions, including a recommendation for dexamethasone use in COVID-19 in their guidelines. Congruent with the study results, the recommendation is limited to patients who require oxygen therapy at any level of care. It is not recommended for patients not requiring such therapy.

Thus, the IDSA recommends glucocorticoid therapy for hospitalized patients with severe COVID-19, with severe disease indicated by an SpO2 ≤ 94% on room air and/or a requirement for supplemental oxygen, mechanical ventilation, or ECMO.1 IDSA further states that dexamethasone 6 mg intravenously or orally be administered until discharge for a maximum of 10 days. If dexamethasone is unavailable, alternative glucocorticoids can be used in equivalent doses. Thus, a total daily dose of 32 mg of methylprednisolone or 40 mg of prednisone may be given.

Of note, the study reviewed here does not address adverse events. In particular, there is no mention of the potential for superinfections due to corticosteroid administration.

REFERENCE

  1. Infectious Diseases Society of America. Infectious Diseases Society of America guidelines on the treatment and management of patients with COVID-19. April 11, 2020. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/#toc-5