Systemic Corticosteroids for COVID-19: Optimal Treatment Duration Is 6 Days

In patients hospitalized with COVID-19, corticosteroid treatment for less than 7 days is the optimal treatment duration for survival, according to systematic review and meta-analysis findings published in Open Forum Infectious Diseases.

Investigators sought to assess the optimal duration for systemic corticosteroid treatment for mortality benefit among patients hospitalized with COVID-19.

The researchers conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies investigating systemic corticosteroid use in patients of all ages for treating COVID-19. The reviewers searched Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Scopus, MEDLINE, the World Health Organization Global Literature on Coronavirus Disease, and CoronaCentral databases, without language restriction, from December 2019 to March 2022. The primary outcome of interest was in-hospital mortality.

Random-effects meta-analyses were used to estimate the effect of corticosteroids on mortality. Optimal duration of corticosteroid treatment adjusted for age, severity of disease, proportion of control group given steroids, and duration of symptoms was assessed with subgroup analyses and meta-analyses.

Investigators found 27 eligible studies (7 RCTs, 20 observational studies) conducted in 8 countries that included 13,404 patients hospitalized with COVID-19 (median age 63 years [interquartile range, 52-71 years]; 35% women) to use in the meta-analysis of mortality. Overall, studies showed that corticosteroid therapy was associated with a protective effect (risk ratio [RR], 0.71; 95% CI, 0.58-0.87). The investigators found the most administered corticosteroid (13/27 studies) was methylprednisolone. Hydrocortisone was used in 2/27 studies and dexamethasone was used in 2/27 RCTs. The type of corticosteroid used in the remaining 10 studies was not specified.

Among the 27 studies characterizing risk of mortality in patients using vs not using systemic corticosteroids, pooled estimates showed mortality from COVID-19 associated with steroid use was 0.71 (95% CI, 0.58-0.87), which suggests a 29% risk reduction in mortality. The researchers noted large amounts of heterogeneity in the between-study variation (I²=69%; P <.0001).

Pooled analysis of 18 studies revealed that the greatest survival benefit from corticosteroids was associated with treatment duration of a median of 6 days (RR, 0.54; 95% CI, 0.39-0.74), suggesting a 46% reduction in mortality risk. Among patients treated for a median of up to 7 days, survival benefit RR was 0.65 (95% CI, 0.51-0.83; I²=63%). No additional survival benefit was associated with a treatment duration of longer than 7 days (RR, 0.64; 95% CI, 0.44-0.93; I²=57%). Age, severity of disease, proportion of control group given corticosteroids, and duration of symptoms did not confound survival benefit.

The greatest reduction in mortality was seen in patients receiving methylprednisolone (RR, 0.57; 95% CI, 0.41-0.79; I²=75%). Subgroup analysis comparing how mortality risk differed in RCTs vs observational studies indicated that study design did not affect mortality risk findings.

Review and meta-analysis limitations include the design nature of a review; publication bias; the inclusion of a small number of studies in the meta-analysis, most of which were observational some of which were low quality; high heterogeneity between studies; and incomplete capture of the benefit of longer corticosteroid courses in the most critically ill.

“The findings of the present study support the positive impact of administration of corticosteroids on mortality in hospitalized patients with COVID-19. Interestingly, administration of corticosteroids for up to a median of fewer than 7 days demonstrated a greater mortality reduction than systemic steroids for equal or more than 7 days,” said study authors. “These findings have important implications for clinical management of COVID-19 patients.”