Efficacy of Corticosteroids in Patients with SARS, MERS and COVID-19: A Systematic Review and Meta-Analysis

Abstract

(1) Background: The use of corticosteroids in critical coronavirus infections, including severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome (MERS), or Coronavirus disease 2019 (COVID-19), has been controversial. However, a meta-analysis on the efficacy of steroids in treating these coronavirus infections is lacking. (2) Purpose: We assessed a methodological criticism on the quality of previous published meta-analyses and the risk of misleading conclusions with important therapeutic consequences. We also examined the evidence of the efficacy of corticosteroids in reducing mortality in SARS, MERS and COVID-19. (3) Methods: PubMed, MEDLINE, Embase, and Web of Science were used to identify studies published until 25 April 2020, that reported associations between steroid use and mortality in treating SARS/MERS/COVID-19. Two investigators screened and extracted data independently. Searches were restricted to studies on humans, and articles that did not report the exact number of patients in each group or data on mortality were excluded. We calculated odds ratios (ORs) or hazard ratios (HRs) under the fixed- and random-effect model. (4) Results: Eight articles (4051 patients) were eligible for inclusion. Among these selected studies, 3416 patients were diagnosed with SARS, 360 patients with MERS, and 275 with COVID-19; 60.3% patients were administered steroids. The meta-analyses including all studies showed no differences overall in terms of mortality (OR 1.152, 95% CI 0.631-2.101 in the random effects model, p = 0.645). However, this conclusion might be biased, because, in some studies, the patients in the steroid group had more severe symptoms than those in the control group. In contrast, when the meta-analysis was performed restricting only to studies that used appropriate adjustment (e.g., time, disease severity), there was a significant difference between the two groups (HR 0.378, 95% CI 0.221-0.646 in the random effects model, p < 0.0001). Although there was no difference in mortality when steroids were used in severe cases, there was a difference among the group with more underlying diseases (OR 3.133, 95% CI 1.670-5.877, p < 0.001). (5) Conclusions: To our knowledge, this study is the first comprehensive systematic review and meta-analysis providing the most accurate evidence on the effect of steroids in coronavirus infections. If not contraindicated, and in the absence of side effects, the use of steroids should be considered in coronavirus infection including COVID-19.

Keywords: Middle East respiratory syndrome (MERS); coronavirus; coronavirus disease 2019 (COVID-19); corticosteroids; severe acute respiratory syndrome (SARS).

Figure 1

Flow chart of literature search.

Figure 2

Association between steroids and mortality of studies about “intervention”. Studies are presented as country study (study [year]). The data are presented for total intervention (a), steroids as an add-on therapy for ribavirin (b), and steroids itself comparing the non-steroid group (c). ^† These are the same as the paper (Lau (2009) [34]) that has two subgroups: one study conducted in Hong-Kong (H1 and H2) and the other study in Toronto (T).

Figure 3

Association between steroids and mortality of studies adjusted for comorbidities or time-dependent conducted studies. Studies are presented as country study (study [year]). Meta-analysis was performed using hazard ratio (HR).

Figure 4

Association between steroids and mortality of studies about “risk factor”. Studies are presented as country study (study [year]). Meta-analysis was performed using an odds ratio (OR).