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

Abstract

Purpose Corticosteroids are standard of care for patients with severe COVID-19. However, the optimal dose is uncertain. We 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 January 7, 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 in absolute risk difference (RD) per 1000 with 95% confidence intervals (CI). Results We included 19 trials, with 9,609 patients. We show that, compared to lower-dose corticosteroids, higher-dose corticosteroids probably reduce mortality (RD 14.8 fewer deaths per 1000 [95% CI 6.0 to 27.9 fewer]; moderate certainty), may reduce the need for mechanical ventilation (RD 10.4 fewer per 1000 [95% CI 19.2 fewer to 3.6 more]; low certainty) and may reduce risk of nosocomial infections (16.7 fewer infections per 1000 [95% CI 5.4 to 25.0 fewer]; low certainty). Conclusions Relatively higher doses of corticosteroids may be beneficial in patients with severe-to-critical COVID-19 without increasing the risk of nosocomial infections.

Dexamethasone doses in patients with COVID‐19 and hypoxia: A systematic review and meta‐analysis

“…This review only included seven out of the 17 RCTs in our review, which may explain the observed difference. 15 Of note, the results from our sensitivity analyses assessing all corticosteroids were similar to their findings, although we could not rule out an increase in mortality.…”

“…Higher versus lower doses of corticosteroids in hospitalised adults with COVID-19 have also been compared in other systematic reviews and meta-analyses of observational studies and RCTs. [14][15][16][17] All used a higher cut-off for high-dose treatment (range 10-20 mg of dexamethasone) than in our review. [14][15][16][17] None assessed days alive without life support, which may be of importance during periods with high caseloads and strained ICU capacity.…”

“…[14][15][16][17] All used a higher cut-off for high-dose treatment (range 10-20 mg of dexamethasone) than in our review. [14][15][16][17] None assessed days alive without life support, which may be of importance during periods with high caseloads and strained ICU capacity. Two systematic reviews exclusively assessed different doses of dexamethasone and found little to no differences in short-term mortality between higher and lower doses based on a cut-off of 10 mg. 16,17 In one systematic review of both observational studies and RCTs comparing different doses of corticosteroids, several RCTs 18,20,28 included in our systematic review were not eligible as high-dose treatment was defined as >100 mg methylprednisolone or >20 mg dexamethasone daily.…”

“…We also hand searched the reference lists of relevant records. [14][15][16][17] All search strings are presented in the Supporting information S1.…”

“…Two systematic reviews exclusively assessed different doses of dexamethasone and found little to no differences in short-term mortality between higher and lower doses based on a cut-off of 10 mg. 16,17 In one systematic review of both observational studies and RCTs comparing different doses of corticosteroids, several RCTs 18,20,28 included in our systematic review were not eligible as high-dose treatment was defined as >100 mg methylprednisolone or >20 mg dexamethasone daily. 14 Pitre et al 15 included 20 RCTs assessing corticosteroids versus placebo or no treatment or different doses of corticosteroids in patients with severe or critical COVID-19 and found that higher doses probably reduced mortality (moderate certainty of evidence). This review only included seven out of the 17 RCTs in our review, which may explain the observed difference.…”