Publications of the Week, September 14

2020-09-14

Corticosteroids in COVID-19

WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, Sterne JAC, Murthy S, Diaz JV, et al. Association Between Administration of Systemic Corticosteroids and Mortality Among Critically Ill Patients With COVID-19: A Meta-analysis. JAMA. 2020 Sep 2. doi: 10.1001/jama.2020.17023. Epub ahead of print. PMID: 32876694.
Prescott HC, Rice TW. Corticosteroids in COVID-19 ARDS: Evidence and Hope During the Pandemic. JAMA. 2020 Sep 2. doi: 10.1001/jama.2020.16747. Epub ahead of print. PMID: 32876693.

There are multiple ongoing clinical trials investigating different therapeutic modalities for patients with coronavirus disease 2019 (COVID-19), including antiviral therapy, anti-inflammatory therapy, convalescent plasma administration, and anticoagulant therapy. Individually, many of these trials have not been sufficiently powered to provide clinically meaningful results, leading investigators to pool findings across studies to increase statistical power.

This meta-analysis prospectively pooled individual patient data from 7 randomized trials that investigated corticosteroid therapy as compared with usual care or placebo for hospitalized critically ill patients with COVID-19 who required respiratory support.

The study objective was to compare the effect of corticosteroid therapy—comprising dexamethasone (20 mg/d [2 trials] or 6 mg/d [1 trial]), hydrocortisone (200 mg/d [3 trials]), or methylprednisolone (80 mg/d [1 trial])—versus usual care or placebo on the outcome of 28-day all-cause mortality.

There were 1703 patients studied (median age, 60 years; 71% males) in this meta-analysis. Administration of systemic corticosteroid therapy was associated with an overall 34% risk reduction in all-cause mortality (odds ratio [OR], 0.66; 95% CI, 0.53-0.82), with 222 deaths in 678 patients (32.7%) randomized to corticosteroids and 425 deaths in 1025 patients (41.5%) randomized to usual care or placebo. This benefit appeared to occur irrespective of whether patients were receiving mechanical ventilation or supplemental oxygen alone. There was consistency of results across the trials (I2 = 15.6%; P = .31 for heterogeneity). According to the type of corticosteroid, there was a statistically significant mortality benefit with dexamethasone, with an OR of 0.64 (95% CI, 0.50-0.82), and a nonsignificant mortality benefit with hydrocortisone, with an OR of 0.69 (95% CI, 0.43-1.12). However, there was no significant mortality benefit observed for methylprednisolone (OR, 0.91; 95% CI, 0.29-2.87), but this finding was based on the results from 1 small trial of 47 patients. There was no significant difference in serious adverse events in patients who received corticosteroid therapy or usual care/placebo.

This meta-analysis of individual patient data from 7 randomized trials found significant mortality benefit with systemic corticosteroid administration in critically ill hospitalized patients with COVID-19 who required respiratory support.

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