The World Health Organization has created a Rapid Evidence Appraisal for COVID-19 Therapies (REACT) working group to perform an ongoing series of meta-analyses. This meta-analysis did a careful search of clinical trial registries to identify all ongoing or completed studies comparing a systemic corticosteroid with placebo or usual care in patients who were critically ill with COVID-19. Trials that included patients with mild or moderate disease or that had not recruited patients were excluded. They identified nine clinical trials, and seven agreed to share data with the REACT team for meta-analysis. Trials were done in six European countries, the United States, Canada, Brazil, New Zealand, Australia, and China. The median age of participants was 60 years, 29% were women, and all but one study required ICU admission. Data from the large UK RECOVERY trial was limited to the subgroup of patients who were mechanically ventilated. Risk of bias was assessed as low using the Cochrane Risk of Bias Tool for six of seven trials. In total, 678 patients were randomized to a corticosteroid and 1,025 to usual care or placebo. There was good consistency across trials in their results, with the I2 of 16% (that means that only 16% of the identified variance was between studies and that 84% was within studies). Corticosteroids significantly reduced mortality (odds ratio 0.66, 95% CI 0.53 to 0.82; risk ratio 0.80, 95% CI 0.70 to 0.91). I think risk ratios are more appropriate because odds ratios are only an approximation of relative risk and are most reliable when outcomes are rare (not the case here). Given a 41.4% mortality rate in the usual care/placebo group, applying the risk ratio of 0.80 yields a 20% mortality reduction to 33.2%, which corresponds to a number needed to treat to prevent one death of 12. They found no difference in outcomes by age, dose of steroid, or duration of illness prior to enrollment. Benefit was smaller for patients not receiving mechanical ventilation at randomization and possibly for those receiving vasoactive agents at randomization. This provides support for use of low-dose corticosteroids in critically ill patients but should not be applied to outpatients or patients not requiring supplemental oxygen.
Written by Mark H. Ebell MD, MS, on September 3, 2020. (Source: The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group. Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis [published online September 2, 2020]. JAMA. 2020.


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