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Meta-Analysis
. 2020 Jul 6;192(27):E756-E767.
doi: 10.1503/cmaj.200645. Epub 2020 May 14.

Efficacy and safety of corticosteroids in COVID-19 based on evidence for COVID-19, other coronavirus infections, influenza, community-acquired pneumonia and acute respiratory distress syndrome: a systematic review and meta-analysis

Zhikang Ye  1 , Ying Wang  1 , Luis Enrique Colunga-Lozano  1 , Manya Prasad  1 , Wimonchat Tangamornsuksan  1 , Bram Rochwerg  1 , Liang Yao  1 , Shahrzad Motaghi  1 , Rachel J Couban  1 , Maryam Ghadimi  1 , Malgorzata M Bala  1 , Huda Gomaa  1 , Fang Fang  1 , Yingqi Xiao  1 , Gordon H Guyatt  2
Affiliations
Meta-Analysis

Efficacy and safety of corticosteroids in COVID-19 based on evidence for COVID-19, other coronavirus infections, influenza, community-acquired pneumonia and acute respiratory distress syndrome: a systematic review and meta-analysis

Zhikang Ye et al. CMAJ. .

Abstract

Background: Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses.

Methods: We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects.

Results: In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non-COVID-19 populations (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio [HR] 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia.

Interpretation: Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality.

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Conflict of interest statement

Competing interests: Bram Rochwerg is an investigator in a trial, supported by a Canadian Institute of Health Research grant, evaluating the effect of corticosteroids in COVID-19 patients. No other competing interests were declared.

Figures

Figure 1:
Figure 1:
Effect of corticosteroids on mortality in patients with acute respiratory distress syndrome without coronavirus disease 2019. Note: CI = confidence interval, M-H = Mantel–Haenszel.
Figure 2:
Figure 2:
Effect of corticosteroids on mortality in patients with severe coronavirus disease 2019. Weights are from random-effects analysis. Note: CI = confidence interval, HR = hazard ratio, IV = inverse variance.
Figure 3:
Figure 3:
Effect of corticosteroids on mortality in patients with severe acute respiratory syndrome. Weights are from random-effects analysis. Note: CI = confidence interval, HR = hazard ratio, IV = inverse variance.
Figure 4:
Figure 4:
Effect of corticosteroids on mortality in patients with influenza. Note: CI = confidence interval, IV = inverse variance, SE = standard error.
Figure 5:
Figure 5:
Effect of corticosteroids on mortality in patients with community-acquired pneumonia. Note: CI = confidence interval, M-H = Mantel–Haenszel.
See this image and copyright information in PMC

Comment in

  • CMAJ. 192:E536.

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