Higher versus lower dose corticosteroids for severe to critical COVID-19: A systematic review and dose-response meta-analysis

Abstract Rationale Corticosteroids are standard of care for patients with severe COVID-19. However, the optimal dose is uncertain. Objective 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 st , 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 GRADE framework to assess the certainty of evidence. We present our results both in relative risk and absolute risk difference (RD) per 1000 with 95% confidence intervals (CI). Results We included 20 trials, with 10,155 patients. We show that, compared to lower-dose corticosteroids, higher-dose corticosteroids probably reduce mortality (RD 14 fewer deaths per 1000 [95% CI 26 to 2 fewer]; moderate certainty), may reduce the need for mechanical ventilation (RD 11.6 fewer per 1000 [95% CI 23.2 fewer to 6.9 more]; low certainty) and may or may not reduce risk of nosocomial infections (16.7 fewer infections per 1000 [95% CI 5.4 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.