Table 1.
Effects of corticosteroids on mortality in patients with COVID-19 - Observational studies.
| Studies | Date (month year) | Design | Population | Main Outcomes | Comments |
|---|---|---|---|---|---|
| Guan et al. [1] | February 2020 | Country : China Retrospective 552 centers Primary outcome: composite of ICU admission, need for invasive MV, mortality Descriptive statistics |
Screened, 7736 Included, 1099 Median age: 46 years Male: 58.1% Invasive MV: 2.3% Admission to ICU, 5% |
In-hospital mortality Corticosteroids: 5/204 (2.5%) No corticosteroids: 10/895 (1.1%) |
No data on type of corticosteroids, dose, duration |
| Zhou et al. [46] | March 2020 | Country : China Retrospective Two centers Primary outcome : in-hospital mortality Logistic regression |
Screened, 813 Included, 191 Median Age : 56 years Male: 62% Median Time to hospitalization: 11 days Median SOFA: 2 Invasive MV: 17% |
In-hospital mortality: Corticosteroids: 26/57 (45.6%) No corticosteroids: 28/134 (20.9%) |
No data on type of corticosteroids, dose, duration |
| Wu et al. [47] | March 2020 | Country : China Retrospective Single center Primary outcome : development of ARDS and mortality Survival analyses, Cox models |
Included, 201 Median age: 51 years Male: 63.7% Invasive MV: 3% |
In-hospital mortality Corticosteroids: 21/50 (46%) No corticosteroids: 21/34 (61.8%) |
Methylprednisolone |
| Zha et al. [48] | March 2020 | Country : China Retrospective Two centers Primary outcome : time to virus clearance Secondary outcomes: time to clinical recovery; hospital length of stay Survival analyses |
Included, 31 Median age: 39 years Male: 68% Time to hospitalization: 4 days |
In-hospital mortality Corticosteroids: 0/11 No corticosteroids: 0/20 |
Methylprednisolone intravenously, 40 mg once or twice per day), administered within 24 h of admission for a median 5 days (interquartile range: 4.5–5.0 days) |
| Wang et al. [49] | April 2020 | Country : China Retrospective Single center Primary outcome: 15-day mortality Cox models |
Included, 548 Median age: 63 years Male: 51% |
15-day mortality Corticosteroids: 65/241 (19.1%) No corticosteroids: 13/205 (6.3%) |
Low-dose glucocorticoid treatment (< 1 mg/ kg) or no glucocorticoid use was associated with a lower hazard ratio of 15 day mortality compared with high-dose treatment (≥ 1 mg/kg) There is no information on the type and duration of corticotherapy |
| Callejas Rubio et al. [50] | April 2020 | Country : Spain Retrospective Single center ferritin > 300 _g/l, IL-6 > 40 pg/ml D-dimers > 1 mg/l Tryglycerides > 300 mg/dl Primary outcome In-hospital mortality Secondary outcome Need for invasive MV Logistic regression |
Included, 92 Mean age: 64 years Male: 63% |
In-hospital mortality Corticosteroids: 6/83 (7.2%) No corticosteroids: 1/9 (11.1%) |
Methylprednisolone pulse therapy for 3 days at dose of 2 mg/kg/d (36,5%), or 250 mg/d(32,9%) or 500 mg/d(31,7%) |
| Ramiro et al. [51] | July 2020 | Country : Netherlands Prospective cohort with historical controls Single center The primary outcome, ≥2 stages of improvement on a 7-item WHO-endorsed scale, or discharge from the hospital Secondary outcomes, hospital mortality and mechanical ventilation. Time to event analyses, Cox models |
Included, 172 (86 in each group) Median age: 67 years Male: 79% MV: 8% |
14 day mortality Corticosteroids: 10/86 (11.6%) No corticosteroids: 33/86 (38.4%) |
Methylprednisolone 250 mg intravenously on day 1, followed by 80 mg on days 2–5, and an option for a 2-day extension if considered necessary and safe Tocilizumab between day 2 and day 5 (single-dose 8 mg/kg intravenous, max 800 mg), if lack of improvement |
| Li et al. [52] | August 2020 | Country : China Retrospective Two cohorts 4 centers Primary outcome : need for invasive MV Secondary outcomes: safety Logistic regression analyses |
Shanghai cohort, screened 311, included 68 Mean age: 58 years Male: 62% Validation cohort, screened 187, included 51 |
Invasive MV Shanghai cohort: Corticosteroids: 5/47 (10.6%) No corticosteroids: 7/21 (33.3%) Validation cohort Corticosteroids: 9/20 No corticosteroids 23/31 (74.2%) |
Methylprednisolone 40–80 mg/d (0.75–1.5 mg/kg/day) for 3 days, then was tapered to 20 mg/day, with a total treatment period of less than 7 days |
| Fernández-Cruz-Cruz et al. [53] | August 2020 | Country : Spain Retrospective, Single center Primary outcome : need for invasive MV Secondary outcomes: safety |
screened 848, included 463 Mean age: 58 years Male: 62% |
In-hospital mortality Corticosteroids: 55/396 (13.9%) No corticosteroids 16/67 (23.9%) |
Methylprednisolone (or the equivalent) 1 mg/kg/day (22.5% of them received steroid pulses later on) and 86 (21.7%) received pulses from the beginning |
| Mikulska et al. [54] | August 2020 | Country : Italy Retrospective, Single center Primary outcome : time to failure, defined as intubation and mechanical ventilation or death, whichever occurred first, within 30 days from the hospital admission |
Screened 295, Included 195, Median age: 67.9 years Male: 67.4% |
Short term mortality Corticosteroids: 13/45 (28.9%) Corticosteroids/ Tocilizumab : 5/56 (8.9%) No corticosteroids : 23/66 (34.8%) |
Methylprednisolone (1 mg/kg for 5 days intravenously, then 0.5 mg/kg for 5 days) Tocilizumab was administered intravenously at the dose of 8 mg/kg (maximum 800 mg), with the possibility of repeating the dose after 24 h if no response was obtained:30 |
| Ruiz-Irastorza et al. [55] | September 2020 | Country : Spain Retrospective Single center Primary outcome, time to mortality, time to mortality or invasive MV Survival analyses, Cox models |
Screened, 343 Included, 242 Mean age: 64 years Male: 62% Mean time to hospitalization: 6.6 days |
In-hospital mortality Corticosteroid: 4/61 (6.6%) No corticosteroids: 18/181 (9.9%). |
Methylprednisolone doses around 1 mg/Kg/d during several days and later as, 125 to 250 mg/d for 3 consecutive days, |
| Salton et al. [56] | September 2020 | Country : Italy multicenter, observational, longitudinal study Primary outcome composite endpoint of admission to ICU, need for invasive MV, or all-cause mortality by day 28 ARDS Berlin definition Survival analysis, Cox models |
Screened, 322 Included, 173 Median age: 65 years Male: 69% Median SOFA: 3 |
28-day mortality Methylprednisolone: 6/83 (7.2%) Control: 21/90 (23.3%) adjusted HR=0.29, 95% CI: 0.12–0.73 |
Methylprednisolone, loading dose of 80 mg intravenously at study entry (baseline), followed by an infusion of 80 mg/d in 240 ml of normal saline at 10 ml/h for at least 8 days, until achieving either a PaO2:FiO2 >350 mmHg or a CRP <20 mg/L; after which, oral administration at 16 mg or 20 mg iv twice daily until CRP reached <20% of the normal range or a PaO2:FiO2 >400 (alternative SatHbO2 ≥95% on room air). |
| Rivera et al. [57] | October 2020 | Country : USA Retrospective Multicenter Primary outcome 30-day mortality Cancer patients with COVID-19 Logistic regression |
Screened, 2956 Included, 2186 Median age: 67 years Male: 49% |
30-day mortality 329 (92%) died within 30 days OR=2.8, 95% CI: 0.77–10.15 Corticosteroids: 30/100 (30%) No corticosteroids: 200/750 (26.7%) |
NA |
| Liu et al. [58] | November 2020 | Country : China Retrospective Five centers Primary outcome 28-day all cause mortality Time to event analyses, Cox models, logistic regression |
Screened, 2537 Included, 774 Median age: 64 years Male: 58% Median SOFA: 11 Invasive MV: 1.4% |
28-day all cause mortality Corticosteroids: 181/409 (44.3%) No corticosteroids: 113/365 (31.0%) |
Methylprednisolone 396/409 Prednisolone 32/409 Dexamethasone 12/409 Hydrocortisone 2/409 Median duration 6 days Median dose 200 mg equivalent Hydrocortisone |
ICU: Intensive care unit; MV: Mechanical ventilation; SOFA: Sequential Organ Failure Assessment; ARDS: Acute respiratory distress syndrome; PaO2: Arterial partial pressure of oxygen; FiO2: Fraction of inspired oxygen; SatHbO2: Oxygen saturation level of hemoglo-bin; CRP: C-reactive protein; NA: not available.