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The association between corticosteroid uses and mortality among severe COVID-19 patients

Published:September 12, 2020DOI:https://doi.org/10.1016/j.jinf.2020.09.005
      To the Editor
      We read with great interest recent meta-analysis
      • Yang 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.
      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-analysis
      • Sterne 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 Group
      Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis.
      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,
      • Sterne 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 Group
      Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis.
      RECOVERY trial
      • Horby P.
      • Lim W.S.
      • Emberson J.R.
      • Mafham M.
      • Bell J.L.
      • Linsell L.
      • et al.
      RECOVERY Collaborative Group
      Dexamethasone in hospitalized patients with COVID-19 - preliminary report.
      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.
      • Sterne 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 Group
      Association between administration of systemic corticosteroids and mortality among critically ill patients with COVID-19: a meta-analysis.
      If we removed RECOVERY trial,
      • Horby P.
      • Lim W.S.
      • Emberson J.R.
      • Mafham M.
      • Bell J.L.
      • Linsell L.
      • et al.
      RECOVERY Collaborative Group
      Dexamethasone in hospitalized patients with COVID-19 - preliminary report.
      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.
      • Lai 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.
      Fig 1
      Fig. 1Association Between Corticosteroids and 28-Day All-Cause Mortality After Excluding RECOVERY Trial.

      Reference

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        • Liu J.
        • Zhou Y.
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        • Zhao Q.
        • Liu J.
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        • Diaz J.V.
        • Slutsky A.S.
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        • Lim W.S.
        • Emberson J.R.
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        • Bell J.L.
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        • et al.
        • RECOVERY Collaborative Group
        Dexamethasone in hospitalized patients with COVID-19 - preliminary report.
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        • Lai C.C.
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        Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges.
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