Efficacy of corticosteroids in COVID-19: An evidence-based approach from the published randomized controlled trials

<h2>Abstract</h2><h3>Background</h3> Despite a considerable volume of research on corticosteroid use in coronavirus disease-2019 (COVID-19), uncertainty and disagreements persist regarding their effectiveness. To address this, we conducted an umbrella review to consolidate the findings and performed an updated meta-analysis to strengthen the existing evidence. <h3>Methods</h3> Databases such as PubMed/MEDLINE, Cochrane library, SCOPUS and Embase were explored from the beginning to January 2024. Meta-analyses and randomized controlled trials (RCTs) assessing safety and efficacy of corticosteroids in COVID-19 patients were included. Methodological quality of included meta-analyses was evaluated using AMSTAR-2 checklist. Corrected covered area (CCA) was calculated to analyse the extent of overlap among primary studies. Cochrane risk of bias tool was used to assess the quality of included RCTs. <h3>Results</h3> Totally, 53 meta-analyses with low to critically low quality were included. Corticosteroid treatment was associated with better ventilator and intensive-care unit free days. A significant decrease in mortality was observed with dexamethasone, but not with any other steroids. There was slight (CCA = 3.67 %) degree of overlap of overall studies, but it was very high for RCTs (CCA = 16.5 %). Updated meta-analysis of 36 RCTs with 18,888 participants found corticosteroids to significantly reduce overall mortality (OR:0.85; 95%CI:0.76–0.95; p = 0.003). Similarly, dexamethasone (OR:0.86; 95%CI:0.76–0.97; p = 0.01) and low dose (≤80 mg) methylprednisolone (OR:0.85; 95%CI:0.76–0.95; p = 0.004) also significantly reduced mortality in COVID-19 patients. Risk of bias of included RCTs were low. <h3>Discussion</h3> There was very high overlap of RCTs among the included meta-analyses. Umbrella review demonstrated decreased mortality with dexamethasone. Updated meta-analysis confirmed mortality reduction with dexamethasone and low dose methylprednisolone in patients with COVID-19. <h3>Prospero registration</h3> CRD42021277160.