Table 1.

Systemic corticosteroids

Clinical Trial Name	Study Type	Study Population	Interventions	Outcomes	Limitations	Conclusion
RECOVERY44	Open-label RCT	Hospitalized patients with COVID-19	2:1 random assignment of usual standard of care (SOC) alone (n = 4321) or standard of care plus oral of IV dexamethasone (n = 2104) 6 mg daily for up to 10 days (or hospital discharge whichever was sooner)	All-cause mortality at 28 days: All patients: 23% in dexamethasone arm versus 26% in SOC arm (RR 0.83; 95% CI, 0.75–0.93; P < 0.001) Receipt of mechanical ventilation (MV) or ECMO at randomization: 29% in dexamethasone vs 41% in SOC (RR 0.64, 95% CI 0.51–0.81) Receipt of supplemental oxygen but not MV at randomization: 23% dexamethasone versus 26% in SOC (RR 0.82; 95% CI,0.72–0.94) Patients not requiring supplemental oxygen at randomization: 18% dex versus 14% SOC (RR 1.19, 95% CI, 0.92–1.55)	Open-label Did not evaluate cause-specific mortality, adverse events and subgroups to look at comorbidities Patients on supplemental oxygen had varying degrees of severity	Dexamethasone reduced 28-day mortality in hospitalized patients who required supplemental oxygen with the greatest benefit being demonstrated in patient requiring MV.
CoDEX52	Open-label RCT	Hospitalized COVID-19 patients with MV within 48 h of meeting criteria for moderate-to-severe ARDs (PaO2/FiO2 ≤ 200 mm HG)	Random 1:1 assignment of dexamethasone 20 mg IV daily for 5 days then 10 mg daily for 5 days or until ICU discharge (n = 151) or SOC (n = 148)	Mean number of days alive and free from MV by Day 28: 7 in dexamethasone arm vs 4 in SOC arm (P = 0.04) No differences between arms in all-cause mortality (56% vs 62%), number of ICU-free days, duration of MV, or score on 6-point OS Mean SOFA score at Day 7: 6.1 in DEX arm vs 7.5 in SOC arm (P = 0.004) Post hoc analysis of probability of death or MV by Day 15: 68% in dexamethasone arm vs 80% in SOC arm (OR 0.46)	Open-label Underpowered Patient discharged before 28 days were not followed for re-hospitalization or death Approximately 25% of patients who were randomized to SOC alone received corticosteroids	Dexamethasone increased the number of days alive and MV free in 28 days in moderate-to-severe ARDS patients with COVID-19.
REMAP-CAP53	Randomized Open-label adaptive trial	Hospitalized COVID-19 patients with severe COVID-19 requiring ICU admission for respiratory or cardiovascular support	1:1:1 randomization of hydrocortisone 50 mg IV every 6 h for 7 days (n = 137), shock-dependent hydrocortisone 50 mg IV every 6 h for up to 28 days (n = 146), or no hydrocortisone (n = 101)	No difference between in median number of organ support-free days at Day 21 (0 in each arm) No difference between arms in in-hospital mortality (30% in fixed-dose hydrocortisone arm vs 26% in shock-dependent hydrocortisone arm vs 33% in no hydrocortisone arm)	Open-label Terminated early therefore underpowered	Hydrocortisone did not increase median number of support-free days
Crothers et al.51	Observational cohort study	27,168 patients admitted to a VA hospital for COVID-19 within 14 days after testing positive	Corticosteroids (95% of patients received dexamethasone) administered within 48 h of admission (n = 7507) Compared with no corticosteroids administered (n = 7433)	Risk of all-cause mortality at 90 days was higher in those who received dexamethasone: For combination of those not on supplemental oxygen and those on low-flow nasal cannula oxygen: HR 1.59; 95% CI, 1.39–1.81 For those not on supplemental oxygen: HR 1.76; 95% CI, 1.47–2.12 For those on low-flow nasal cannula oxygen: HR 1.08; 95% CI, 0.86–1.36	Retrospective observational study Variation in other therapies patients received	Dexamethasone in hospitalized COVID-19 patients who were receiving low-flow nasal cannula during the first 48 h of admission did not show a mortality benefit. There was an increase in mortality seen in patients who received dexamethasone who were not on supplemental oxygen within the first 48 h after admission.