Efficacy and safety of systematic corticosteroids among severe COVID-19 patients: a systematic review and meta-analysis of randomized controlled trials

Abstract

The benefits and harms of corticosteroids for patients with severe coronavirus disease 2019 (COVID-19) remain unclear. We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials from December 31, 2019 to October 1, 2020 to identify randomized controlled trials (RCTs) that evaluated corticosteroids in severe COVID-19 patients. The primary outcome was all-cause mortality at the longest follow-up. Secondary outcomes included a composite disease progression (progression to intubation, ventilation, extracorporeal membrane oxygenation, ICU transfer, or death among those not ventilated at enrollment) and incidence of serious adverse events. A random-effects model was applied to calculate risk ratio (RR) with 95% confidence intervals (CIs). We used the Grading of Recommendations Assessment, Development, and Evaluation approach to evaluate the certainty of the evidence. Seven RCTs involving 6250 patients were included, of which the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial comprised nearly 78% of all included subjects. Results showed that corticosteroids were associated with a decreased all-cause mortality (27.3 vs. 31.1%; RR: 0.85; 95% CI: 0.73-0.99; P = 0.04; low-certainty evidence). Trial sequential analysis suggested that more trials were still required to confirm the results. However, such survival benefit was absent if RECOVERY trial was excluded (RR: 0.83; 95% CI: 0.65-1.06; P = 0.13). Furthermore, corticosteroids decreased the occurrence of composite disease progression (30.6 vs. 33.3%; RR: 0.77; 95% CI: 0.64-0.92; P = 0.005), but not increased the incidence of serious adverse events (3.5 vs. 3.4%; RR: 1.16; 95% CI: 0.39-3.43; P = 0.79).

Fig. 1

PRISMA flowchart for the identification, screening, eligibility, and inclusion of trials

Fig. 2

Forest plot comparing corticosteroids treatment vs. no corticosteroids on all-cause mortality in severe COVID-19 patients. a Forest plot of all-cause mortality including all the seven trials. b Forest plot of all-cause mortality without RECOVERY trial. M–H Mantel–Haenszel, CI confidence interval, df degrees of freedom

Fig. 3

TSA for all-cause mortality comparing corticosteroids vs. no corticosteroids. TSA was performed with control arm event (no corticosteroids) proportion of 31.1%, relative risk reduction of 20%, α of 5% (two sided), and β of 20%. The required information size was obtained as 9097. Z curve crossed the conventional boundary but not crossed the trial sequential monitoring boundary; meanwhile, it not reached the required information size