The association between corticosteroid uses and mortality among severe COVID-19 patients
Authors: Hung-Jen Tang, Chih-Cheng Lai
Journal: Journal of Infection (2020)

We read with great interest recent meta-analysis1Yang Z. Liu J. Zhou Y. Zhao X. Zhao Q. Liu J. The effect of corticosteroid treatment on patients with coronavirus infection: a systematic review and meta-analysis.J Infect. 2020; 81: e13-e20Abstract Full Text Full Text PDF PubMed Scopus (244) Google Scholar by Yang et al., in which they analyzed a total of 5270 patients from 15 studies and found that the use of corticosteroid treatment was associated higher mortality, longer length of stay and a higher rate of bacterial infection among patients with coronavirus infection. By contrast, another meta-analysis2Sterne J.A.C. Murthy S. Diaz J.V. Slutsky A.S. Villar J. Angus D.C. et al.WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working GroupAssociation between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis.JAMA. 2020; (Online ahead of print)https://doi.org/10.1001/jama.2020.17023Crossref Scopus (1621) Google Scholar including 7 randomized controlled trials of a total 1703 patients by WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working group demonstrated that administration of systemic corticosteroid was associated with a lower 28-day all-cause mortality, compared with usual care or placebo (OR, 0.66; 95% CI, 0.53–0.82 based on a fixed-effect model). Although the difference between these two studies may be attributed to different study design and populations, we have one serious concern about the findings of REACT Working group . In that meta-analysis,2Sterne J.A.C. Murthy S. Diaz J.V. Slutsky A.S. Villar J. Angus D.C. et al.WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working GroupAssociation between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis.JAMA. 2020; (Online ahead of print)https://doi.org/10.1001/jama.2020.17023Crossref Scopus (1621) Google Scholar RECOVERY trial3Horby P. Lim W.S. Emberson J.R. Mafham M. Bell J.L. Linsell L. et al.RECOVERY Collaborative GroupDexamethasone in hospitalized patients with COVID-19 - preliminary report.N Engl J Med. 2020; (NEJMoa2021436Online ahead of print.)https://doi.org/10.1056/NEJMoa2021436Crossref Scopus (6807) Google Scholar comprised 59% (n = 1007) patients, and it was suspected to exert most influence on the results of this meta-analysis. In the leave-one-out sensitivity analysis, we can find that the magnitude of association between corticosteroid and mortality was significantly influenced by RECOVERY trial.2Sterne J.A.C. Murthy S. Diaz J.V. Slutsky A.S. Villar J. Angus D.C. et al.WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working GroupAssociation between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis.JAMA. 2020; (Online ahead of print)https://doi.org/10.1001/jama.2020.17023Crossref Scopus (1621) Google Scholar If we removed RECOVERY trial,3Horby P. Lim W.S. Emberson J.R. Mafham M. Bell J.L. Linsell L. et al.RECOVERY Collaborative GroupDexamethasone in hospitalized patients with COVID-19 - preliminary report.N Engl J Med. 2020; (NEJMoa2021436Online ahead of print.)https://doi.org/10.1056/NEJMoa2021436Crossref Scopus (6807) Google Scholar although the mortality rate of patients receiving corticosteroid was numerically lower than that of control group, the difference did not reach statistical significance (OR, 0.78; 95% CI, 0.56–1.07, Fig. 1). Moreover, the finding was consistent in the sensitivity analysis and in random-effect model analysis (OR, 0.78; 95% CI, 0.54–1.12). Therefore, we suggest the use of corticosteroid for patients with severe COVID-19 should be cautious. Further large-scale study is warranted to clarify this issue during this COVID-19 pandemic.4Lai C.C. Shih T.P. Ko W.C. Tang H.J. Hsueh P.R. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges.Int J Antimicrob Agents. 2020; 55105924Crossref PubMed Scopus (3832) Google Scholar