Table 1 Study characteristics

1

Angus

34

REMAPt ^b

Hydrocortisone  < 1 mg/kg ED

403

ICU patients

x

x

x

Risk of bias^d

Two hydorcoritsone dosing resulted high probabilities of superiority with regard to the odds of improvement in organ support–free days within 21 days, compared to standard of care

2

Bani-Sadr

39

Cohort with historical controls

Prednisolone or Methylprednisolone  ≥ 1 mg/kg ED

319

Hospitalized patients

x

x

x

4

Addition of corticosteroids to our institution’s COVID-19 treatment protocol was associated with a significant reduction in hospital mortality in the “after” period

3

Cao

80

Retrospective Observational

Unknown

102

Hospitalized patients

x

5

Patient characteristics seen more frequently in those who died were development of systemic complications following onset of the illness and the severity of disease requiring admission to the ICU

4

Chen Zu

Retrospective Observational

Unknown

267

Hospitalized patients

x

x

7

Corticosteroid treatment is associated with prolonged viral RNA shedding and should be used with caution

5

Chroboczek

72

Retrospective Observational

Unknown

70

Hospitalized patients

x

6

Corticosteroids therapy affected the risk of intubation with a risk difference of − 47.1% (95% CI − 71.8 to − 22.5)

6

Dequin

35

Randomized controlled trial

Methylprednisolone or hydrocortisone  < 1 mg/kg ED

149

ICU patients with respiratory failure

x

x

x

x

Risk of Bias^d

Low-dose hydrocortisone, compared with placebo, did not significantly reduce treatment failure (defined as death or persistent respiratory support) at day 21 in critically ill patients

7

Fadel

38

Quasi experimental

Methylprednisolone  ≥ 1 mg/kg ED

213

Moderate-to-severe CoVID patients

x

x

x

6

An early short course of methylprednisolone in patients with moderate-to-severe COVID-19 reduced escalation of care and improved clinical outcomes

8

Fang Mei

40

Retrospective Observational

Methylprednisolone  < 1 mg/kg ED

78

Hospitalized patients

x

5

Low-dose corticosteroid therapy may not delay viral clearance in patients with COVID-19

9

Feng Ling

66

Retrospective Observational

Unknown

476

Hospitalized patients

x

x

5

Differences in AT II receptor inhibitors use were associated with different severities of disease. Multiple lung lobes involvement and pleural effusion were associated with the severity of COVID-19. Advanced age (> 75 yr) was a risk factor for mortality

10

Fernandez

41

Retrospective Observational

Methylprednisolone  ≥ 1 mg/kg ED

463

Patients with ARDS hyperinflammation

x

x

5

Glucocorticoid use is associated with increased survival and improved mortality rates in severe CoVID-19 patients

11

Gazzaruso

42

Retrospective Observational

Methylprednisolone or prednisone  < 1 mg/kg ED

219

Hospitalized patients

x

x

3

Antirheumatic drugs, probably steroids included, may modulate inflammation and avoid a hyperinflammation that leads to severe complications and death in subjects with COVID-19

12

Gong Guan

43

Retrospective Observational

Methylprednisolone  ≥ 1 mg/kg ED

34

Hospitalized Patients < 50 years

x

x

6

Corticosteroids therapy can effectively release COVID‐19 symptoms, improve oxygenation and prevent disease progression. However, it can prolong the negative conversion of nucleic acids

13

Horby

23

Randomized controlled trial

Dexamethasone  < 1 mg/kg ED

6425

Hospitalized patients

x

x

x

Risk of bias^d

The use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization but not among those receiving no respiratory support

15

Hu Wang

44

Retrospective Observational

Prednisolone or methylprednisolone  > 1 mg/kg ED

308

Hospitalized patients

x

x

4

Glucocorticoid therapy did not significantly influence the outcomes nor the adverse events of COVID-19 pneumonia

16

Huang Song

45

Retrospective Observational

Methylprednisolone 2 study groups: High: ≥ 1 mg/kg ED Low: < 1 mg/kg ED

64

Hospitalized patients

x

4

There were no significant differences in the duration of severe illness or the number of days on high level respiratory support between low-dose and high-dose methylprednisolone group. The mean number of days in the hospital was higher in the high-dose group

14

Huang Yang

81

Retrospective Observational

Unknown

60

Severe CoVID patients

x

5

There were no statistically significant differences in immunoglobulin therapy and GCs therapy between the improvement and deterioration subgroups

17

Jeronimo

36

Randomized controlled trial

Methylprednisolone  < 1 mg/kg ED

393

Hospitalized patients

x

x

x

x

Risk of bias^d

Results showed no overall reduction in mortality in 28 days. Patients over 60 years presented a lower mortality in a subgroup analysis

18

Keller

73

Retrospective Observational

Unknown

1806

Early hospitalized patients

x

x

6

In high CRP group, glucocorticoids show significantly reduced risk of mortality or mechanical ventilation (odds ratio, 0.23; 95% CI, 0.08–0.70). In low CRP group, glucocorticoids were associated with significantly increased risk of mortality or mechanical ventilation (OR, 2.64; 95% CI,1.39–5.03)

19

Li Hu

46

Retrospective Observational

Methylprednisolone high and low ED

203

Hospitalized patients

x

5

A dose response relation is suggested for corticosteroids on viral shedding. In addition, high-dose but not low-dose corticosteroids were found to potentially increase mortality in severe patients

20

Li Li

47

Retrospective Observational

Methylprednisolone or prednisone  < 1 mg/kg ED

475

Non-severe CoVID patients

x

x

x

x

5

Early, low-dose, and short-term corticosteroids therapy was associated with worse clinical outcomes

21

Li Zhou

48

Retrospective Observational

Methylprednisolone  > 1 mg/kg ED

187

Radiologically progressive CoVID patients

x

x

6

Short-term, low-to-moderate-dose corticosteroids benefits patients with LDH levels of less than two times the ULN, who may be in the early phase of excessive inflammation

22

Lui Fang

49

Retrospective Observational

Methylprednisolone ≥ 1 mg/kg ED

101

Hospitalized patients

x

3

The majority of patients present primarily with fever and typical manifestations on chest imaging. Middle-aged and elderly patients with underlying comorbidities are susceptible to respiratory failure and may have a poorer prognosis

23

Liu Zhang

81

Retrospective Observational

Unknown

1190

Hospitalized patients

x

5

Treatment with glucocorticoids increased the risk of progression from not severe to severe disease (OR 3.79, 95% CI 2.39–6.01)

24

Liu Zheng

50

Retrospective Observational

Methylprednisolone ≥ 1 mg/kg ED

101

Hospitalized patients

x

x

5

Timely and appropriate application of methylprednisolone in severe and critical patients may improve outcomes and lung function without negative impacts on specific SARS-CoV-2 IgG production

25

Lu Chen

51

Retrospective Observational

Methylprednisolone, hydrocortisone or dexamethasone  > 1 mg/kg ED

244

Hospitalized patients

x

x

7

Limited effect of corticosteroid therapy could pose to overall survival of critically ill patients with COVID-19. Given the adverse effects, corticosteroid therapy must be commenced with caution, and prudent dosage should be promoted under certain circumstances

26

Ma Qi

52

Retrospective Observational

Methylprednisolone 2 study groups:

High: ≥ 1 mg/kg ED

Low: < 1 mg/kg ED

72

Severe and critical patients

x

x

x

x

6

Corticosteroids cannot reduce the hospital mortality and is not associated with delayed viral clearance, but it could relieve the inflammatory storm and improve clinical symptoms in brief. Patients with severe COVID-19 could benefit from low-dose corticosteroids

27

Ma Zeng

53

Retrospective Observational

Methylprednisolone ≥ 1 mg/kg ED

450

Severe and non-severe patients

x

x

x

x

x

4

Corticosteroids use may be accompanied by increased use of antibiotics, longer hospitalization, and prolonged viral shedding

28

Majmundar

54

Retrospective Observational

Prednisolone, dexamethasone, methylprednisolone

 > 1 mg/kg ED

205

Hospitalized patients

x

x

x

x

6

Corticosteroids were associated with a significantly lower risk of the ICU transfer, intubation, or in-hospital death,

29

Mikulska

55

Retrospective Observational

Methylprednisolone high and low ED

215

Hospitalized non-intubated patients

x

x

6

Early adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in non-intubated patients

30

Nelson

56

Retrospective Observational

Methylprednisolone ≥ 1 mg/kg ED

117

ICU patients on mechanical ventilation

x

x

x

8

Methylprednisolone was associated with increased ventilator-free days and higher probability of extubation in a propensity-score matched cohort

31

Rodriquez

57

Retrospective Observational

Methylprednisolone ≥ 1 mg/kg ED

1014

Hospitalized patients

x

x

x

7

Tocilizumab should be prioritized for being tested in randomized trials targeting patients with data suggestive of a hyperinflammatory state. The results for PDC were less consistent but are also encouraging

32

Rubio

68

Retrospective Observational

Unknown

92

ICU and general ward patients

x

x

5

The early use of GC pulses could reduce the use of tocilizumab and might decrease events such as intubation and death

33

Salton

58

Retrospective Observational

Methylprednisolone ≥ 1 mg/kg ED

173

ARDS patients

x

x

x

8

Per-protocol administration of prolonged low-dose methylpred-nisolone treatment is associated with a significantly lower hazard of death, reduced ICU burden and decreased ventilator dependence

34

Shen Zheng

59

Retrospective Observational

Methylprednisolone unknown dose

325

Hospitalized patients

x

4

COVID-19 cases in Shanghai were imported. Rapid identification and effective control measures helped to contain the outbreak and prevent community transmission

35

Shi Wu

71

Retrospective Observational

Unknown

99

Hospitalized patients

x

4

SARS-CoV-2 RNA clearance time was associated with sex, disease severity and lymphocyte function. The current antiviral protocol and low-to-moderate dosage of corticosteroid had little effect on the duration of viral excretion

36

Tomazini

37

Randomized controlled trial

Dexamethasone

 > 1 mg/kg ED

299

ICU patients with moderate-to-severe ARDS

x

x

x

Risk of bias^d

Dexamethasone plus standard care compared with standard care alone resulted in a significant increase in the number of ventilator-free days (days alive and free of mechanical ventilation) over 28 days

37

Wang Jiang

60

Retrospective Observational

Methylprednisolone

 > 1 mg/kg ED

46

Severe hospitalized patients

x

x

x

7

early, low-dose and short-term application of methylprednisolone was associated with better clinical outcomes in severe CoVID-19 patients and should be considered before onset of ARDS

38

Wang Yang

67

Retrospective Observational

Unknown

69

Hospitalized patients

x

4

COVID-19 shows frequently fever, dry cough, and increase of inflammatory cytokines, and induced a mortality rate of 7.5%. Older patients or those with comorbidities are at higher risk of death

38

Wang Zhang

69

Retrospective Observational

Unknown

548

Not Reported

x

6

Low-dose or no glucocorticoid treatment was associated with a lower hazard compared with high-dose treatment (≥ 1 mg/kg) for 15 days in hospital death

40

Wu Chen

61

Retrospective Observational

Methylprednisolone unknown dose

201

Hospitalized patients

x

4

Treatment with methylprednisolone may be beneficial for patients who develop ARDS

41

Wu Huang

62

Retrospective Observational

Methylprednisolone

 < 1 mg/kg ED

1763

Severe or critical patients

x

7

Corticosteroid use was not associated with beneficial effect in reducing in-hospital mortality for severe or critical cases in Wuhan

42

Xu Chen

63

Retrospective Observational

Methylprednisolone

 < 1 mg/kg ED

113

Hospitalized patients

x

x

5

Prolonged SARS-CoV-2 RNA shedding was associated with male sex (P = .009), old age (P = .033), concomitant hypertension (P = .009), delayed admission to hospital after illness onset (P = .001), severe illness at admission (P = .049), invasive mechanical ventilation (P = .006) and corticosteroid treatment (P = .025)

43

Yang Lipes

64

Retrospective Observational

Methylprednisolone, hydrocortisone or dexamethasone

 > 1 mg/kg ED

15

ICU patients

x

x

6

Possible short-term clinical improvements with corticosteroid. Emphasis the urgent need for high-quality studies on steroids and outcome in critically ill COVID-19 patients

44

Zha Li

65

Retrospective Observational

Methylprednisolone

 < 1 mg/kg ED

31

Hospitalized patients

x

x

x

5

No evidence of clinical benefit of corticosteroids was found for those without acute respiratory distress syndrome. Virus clearance may be slower in people with chronic HBV infections