Higher- versus Lower-Dose Corticosteroids for Severe to Critical COVID-19: A Systematic Review and Dose-Response...

Rationale: Corticosteroids are standard of care for patients with severe coronavirus disease (COVID-19). However, the optimal dose is uncertain. Objectives: To compare higher doses of corticosteroids with lower doses in patients with COVID-19. Methods: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, MedRxiv, and Web of Science from inception to August 1, 2022, for trials that randomized patients with severe-to-critical COVID-19 to corticosteroids, standard care, or placebo. Reviewers, working in duplicate, screened references, extracted data, and assessed risk of bias using a modified version of the Cochrane risk of bias 2.0 tool. We performed a dose-response meta-analysis and used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework to assess the certainty of evidence. We present our results both in relative risk and absolute risk difference per 1,000, with 95% confidence intervals (CIs). Results: We included 20 trials, with 10,155 patients. We show that, compared with lower-dose corticosteroids, higher-dose corticosteroids probably reduce mortality (absolute risk difference, 14 fewer deaths per 1,000 [95% CI, 26 fewer to 2 fewer]; moderate certainty) and may reduce the need for mechanical ventilation (absolute risk difference, 11.6 fewer per 1,000 [95% CI, 23.2 fewer to 6.9 more]; low certainty). The effect of corticosteroids on nosocomial infections is uncertain (16.7 fewer infections per 1,000 [95% CI, 5.4 fewer to 25.0 fewer]; very low certainty). Conclusions: Relatively higher doses of corticosteroids may be beneficial in patients with severe-to-critical COVID-19 and may not increase the risk of nosocomial infections.