Table 1.
Review of Major Coronavirus Disease 2019 Series That Used Corticosteroids as Therapy
| Agent [Ref] | Country | Study Design | Target Population (n)a | Endpoint Measured | Outcome and Multivariable Analysis | Infectious Complications | Conclusion or Recommendation | Strength of Evidenceb |
|---|---|---|---|---|---|---|---|---|
| Dexamethasone [21] | United Kingdom | Open-label, RCT | Hospitalized patients (2104) | Mortality at 28 days | 22.9% vs 25.7% favoring dexamethasone, age-adjusted rate ratio 0.83 (95% CI, .75 to .93) | Not reported | Mortality benefit favoring dexamethasone, strongest effect on those receiving mechanical ventilation | A |
| Hydrocortisone [56] | France | RCT, double-blind | Critically ill patients (76) | Death or persistent mechanical ventilation or high-flow nasal cannula at day 21 | 42.1% vs 50.7% favoring hydrocortisone, difference of proportions –8.6% (95% CI, –24.9% to 7.7%; P = .29) | 37.3% for hydrocortisone and 41.1% for placebo (HR, 0.81; 95% CI, .49 to 1.35; P = .42) | No significant difference in primary outcome; study stopped early (underpowered) | A |
| Methylprednisolone [57] | Brazil | RCT, double-blind | Hospitalized patients with severe or critical COVID-19 (194) | Mortality at 28 days | 37.1% for methylprednisolone vs 38.2% (P = .629) | Not reported | No difference in overall mortality | A |
| Dexamethasone [58] | Brazil | Open-label, RCT | Hospitalized patients with moderate to severe COVID-19 (151) | Ventilator-free days during first 28 days | More ventilator-free days for dexamethasone (difference 2.26; 95% CI, .2 to 4.38; P = .04); no difference in all-cause mortality at 28 days (56.3% vs 61.5%; HR, 0.97; 95% CI, .72 to 1.31; P = .85) | 21.9% of dexamethasone and 29.1% of usual care had secondary infections | Dexamethasone was associated with more days off of a ventilator; however, in this study, a mortality benefit was not seen | A |
| Methylprednisolone [59] | Iran | RCT, single-blind | Hospitalized patients with SpO2 <90%, elevated CRP, and elevated interleukin-6, though excluded if acute respiratory distress syndrome, SpO2 <75%, positive procalcitonin or positive troponin (34) | Time to clinical improvement and discharge or death, whichever came first | Methylprednisolone significantly associated with reduced time to primary outcome (11.6 ± 4.8 days vs 17.6 ± 9.8 days, P = .006); mortality rate lower for methylprednisolone group (5.9% vs 42.9%, P < .001) | Not well defined | In a small study with a highly specific group, methylprednisolone showed a benefit | A |
| Methylprednisolone [60] | United States (Michigan) | Single pre-test post-test quasiexperimental study | Hospitalized patients requiring supplemental oxygen (132) | Composite of escalation to ICU or all-cause in-hospital mortality | Primary composite endpoint occurred in 34.9% vs 54.3% (P = .005), favoring early steroid group; after multivariable adjustment, early corticosteroids were independently associated with a reduction in composite outcome at day 14 (OR, 0.4; 95% CI, .22 to .77) | Not reported | Early steroid use was associated with improved outcomes in this nonrandomized trial | B |
| Methylprednisolone [61] | Spain | Retrospective cohort study | Hospitalized patients (396) | In-hospital mortality | Patients treated with steroids had lower mortality than those treated with standard of care (13.9% vs 23.9%; HR, 0.51; 95% CI, .27 to .96; P = .044) | Not reported | Steroid use associated with lower mortality in this nonrandomized trial; the finding persisted after propensity score matching | B |
| Corticosteroids [62] | United States (New York City) | Retrospective cohort study | Hospitalized patients; compared those who received steroids within 48 hours of admission compared with those who never received steroids (140) | Composite of in-hospital mortality or in-hospital mechanical ventilation | Early glucocorticoids were not associated with decreased in-hospital mortality, though among subgroup with CRP >20 mg/dL was associated with reduced mortality or mechanical ventilation (adjusted OR, 0.20; 95% CI, .06 to .67) | Not reported | Steroid use was not associated with improved outcomes overall; among those with elevated CRP, steroid use was associated with improved outcomes | B |
| Corticosteroids [63] | China | Retrospective cohort study | Hospitalized patients (158) | In-hospital mortality | Patients who received corticosteroids had higher mortality (45.6% vs 11.5%, P < .0001); after propensity matching; there was no difference in mortality | There were more nosocomial infections among those treated with steroids (7.0% vs 2.9%, P = .02) | This nonrandomized trial found no benefit of steroids for treatment of COVID-19 | B |
| Corticosteroids [64] | Italy | Retrospective cohort study | Hospitalized patients with severe COVID-19 (170) | Mortality at day 30 from hospital admission | 35% in corticosteroid group and 31% in nonsteroid group died within 30 days of hospital admission; multivariable analysis adjusted OR, 0.59; 95% CI, .20 to 1.74; P = .33 | 17% of overall cohort had bacterial superinfections; hazard was higher for those who received steroids but not statistically significant (HR, 1.55; 95% CI, .95 to 2.55; P = .08) | This nonrandomized trial found no mortality benefit of corticosteroids for severe COVID-19 | B |
| Corticosteroids [55] | China | Retrospective cohort study | Hospitalized patients (126) | Hospital length of stay | After matching, among nonsevere group, steroid use associated with increased length of stay (19.0 days vs 11.5 days, P < .001); among severe group, no significant difference in length of stay (14.0 days vs 16.0 days, P = .883) | Unable to report infection rates, but antibiotic use higher among those who received steroids (P < .001) | This nonrandomized trial found no benefit of steroid use for COVID-19 and found longer hospital stay for nonsevere patients who received steroids compared with matched nonsteroid recipients | B |
| Corticosteroids [65] | United States (New York City) | Retrospective cohort study | Hospitalized patients with severe COVID-19 (SpO2/fiO2 <440) (60) | Composite outcome of ICU transfer, intubate, or death | In adjusted analysis, those who received steroids were less likely to have had a primary outcome (adjusted HR, 0.15; 95% CI, .07 to .33; P < .001) | Not reported | In this nonrandomized study of patients with severe COVID-19, steroid administration was associated with improved outcomes | B |
| Corticosteroids [66] | China | Retrospective cohort study | Hospitalized patients with severe (requiring supplemental oxygen) or critical (shock, mechanical ventilation, or ICU-level care) COVID-19 (531) | In-hospital mortality | In multivariable analysis, steroid use was independently associated with in-hospital mortality (HR, 1.77; 95% CI, 1.08 to 2.89; P = .023) | Not reported | In this nonrandomized study of severe and critically ill patients with COVID-19, steroid use was associated with an increased risk of death | B |
| Methylprednisolone [67] | China | Retrospective cohort study | Hospitalized patients with severe or critical COVID-19 (140) | Progression from severe to critical illness | In multivariate analysis, methylprednisolone was associated with less risk of progression to critical illness (OR, 0.054; 95% CI, .017 to .173; P < .001); in a subgroup analysis, the finding held for individuals aged <65 years but not for those aged >65 years | Not reported | In this nonrandomized study, steroid use was associated with less progression to critical illness | B |
Abbreviations: CI, confidence interval; COVID-19, coronavirus disease 2019; CRP, C-reactive protein; fiO2, fraction of inspired oxygen; HR, hazard ratio; ICU, intensive care unit; OR, odds ratio; RCT, randomized, controlled trial; Ref, reference; SpO2, peripheral capillary oxygen saturation.
an = number of patients in study who received immunomodulatory therapy.
bStrength of evidence graded as: A = from a randomized, controlled trial; B = from a nonrandomized study.