Introduction We conducted a comprehensive literature review to synthesize evidence for the relationship between corticosteroid use and mortality in patients with COVID-19. Methods The PUBMED, EMBASE, and Cochrane Library were searched from inception to March 13, 2021. We searched and analyzed randomized controlled trials (RCTs) and observational studies (OSs) that examined corticosteroid use in patients with COVID-19. The primary outcome was in-hospital mortality, while the secondary outcome was the need for mechanical ventilation (MV) and serious adverse events. Results A total of 11 RCTs and 44 OSs involving 7893 and 41,164 patients with COVID-19 were included in the study. Corticosteroid use was associated with lower COVID-19 mortality in RCTs, but was not statistically significant (OR 0.91, 95% CI 0.77–1.07; I² = 63.4%). The subgroup analysis of pulse dose corticosteroid showed survival benefit statistically (OR 0.29, 95% CI 0.15–0.56). Moreover, the corticosteroid use may reduce the need for MV (OR 0.67, 95% CI 0.51–0.90; I² = 7.5%) with no significant increase in serious adverse reactions (OR 0.84, 95% CI 0.30–2.37; I² = 33.3%). In addition, the included OSs showed that the pulse dose (OR 0.66, 95% CI 0.45–0.95; I² = 30.8%) might lower the mortality in patients with COVID-19. The pulse dose of methylprednisolone (OR 0.60, 95% CI 0.45–0.80; I² = 0%) had a beneficial effect on survival. It was especially significant when the duration of pulse methylprednisolone use was less than 7 days (OR 0.59, 95% CI 0.43–0.80; I² = 0%). Conclusions This meta-analysis indicated that corticosteroid use might cause a slight reduction in COVID-19 mortality. However, it could significantly reduce the MV requirement in patients with COVID-19 and restrict serious adverse events. Additionally, the pulse dose of methylprednisolone for less than 7 days may be a good treatment choice for patients with COVID-19.

The transcription factor forkhead box O1 (FOXO1) induces pancreatic islet beta cell endoplasmic reticulum stress and is involved in fatty-acid-induced insulin-secretion defects. Cask is a downstream target gene of FOXO1. Using INS-1 cells with palmitate-induced insulin-release defects, we investigated the relationship between FOXO1 and Cask. The expression levels and location of calcium/calmodulin-dependent serine protein kinase (CASK) and FOXO1 were evaluated by real-time PCR, western blotting and immunofluorescence. The regulation of Cask by FOXO1 was examined using chromatin immunoprecipitation (ChIP) and luciferase assays. Potassium-stimulated insulin-secretion assays were used to verify the function of INS-1 cells and islets. Electron microscopy was used to establish the anchoring process of the insulin granules after CASK knockdown in islets. Palmitic acid reduced CASK levels and increased FOXO1 levels. ChIP and luciferase assays demonstrated FOXO1 binding with the Cask promoter, which was enhanced by palmitate treatment. CASK knockdown reduced insulin release in INS-1 cells and primary islets, and Cask overexpression reversed the palmitate-induced insulin reduction. CASK knockdown attenuated forskolin-enhanced insulin release, but Cask overexpression did not change the insulin-secretion suppression induced by nifedipine. In pancreatic islet beta cells, CASK knockdown reduced the anchoring of insulin vesicles to cell membranes. The induction of beta cell insulin-secretion defects by fatty acids is mediated, at least in part, by FOXO1 via downregulation of Cask expression. It is characterised mainly as an obstruction of the anchoring of insulin granules to beta cell membranes.