Table 5.

Trials and corticosteroid (CS)-related adverse effects (randomized trials in blue, retrospective/observational trials in yellow, and meta-analysis in orange).

Trial Name	Steroid Used, Dosing	Initiation (Days)	Duration (Days)	Hyperglycemia	GI	CNS	CVS	Secondary Infections	Other
Jeronimo CMP et al. MetCOVID [30]	MP 0.5 mg/kg bid vs. placebo		5	MP group: ↑insulin				No difference in BC positivity
Corral-Cudino et al., GLUCOCOVID [13]	MP 40 mg bid × 3 d, then 20 mg bid x 3 d	Min 7 after Sx onset	6	MP: ↑ Glu (p = 0.015)				MP: ↑ Secondary infections (p = 0.637)
Tang X et al. [42]	1 mg/kg/d MP vs. no MP	Median time 8 (6–16) after Sx onset	7	no MP: ↑ Glu (p = 0.313)	Either group: No stress ulcers/GI bleed	Either group: No delirium		MP: ↑ VAP (p = 0.557)
Papamanoli A et al. [43]	Median daily 160 mg MP (120–180)	10 from Sx onset, 2 from admission, 1 from HFNC initiation	Median: 10 incl tapering		GI bleed: no difference			Bacteremia, HAP/VAP: No difference
Salton F et al. [22]	80 mg MP loading dose, then 80 mg/day cont infusion		Min 8	MP: ↑ Glu		MP: Mild agitation more common
Yuan M et al. [46]	MP max dose 52.5 mg, nonsevere pts	Median 8.3 from Sx onset	Median duration 10.8					CS vs. no CS: No significant difference in secondary infections
RECOVERY trial [16]	dexa 6 mg/day pos or iv			2/2104 pts	GI bleed: 1/2104 pts	Psychosis: 1/2104
Tomazini BM et al. CoDEX trial [27]	20 mg dexa iv × 5 d, then 10 mg dexa × 5 d or until ICU discharge		≤10	Insulin need: Dexa: 31.1% vs. SOC 28.3%				Dexa 21.9% vs. SOC: 29.1%	Other serious: dexa 3.3% vs. 6.1% SOC
Dequin P-F et al. [28]	Cont iv: 200 mg HC × 7d, then 100 mg × 4d, then 50 mg × 3 d		Total max 14					D28: nosocomial infection: 37.3% HC vs. 41.1%placebo (p = 0.42). D28 VAP: 29% HC vs. 27.4% placebo. D28 bacteremia: 6.6% HC vs. 11% placebo	HC:3 serious AE considered unrelated: Cerebral vasculitis, Cardiac arrest 2nd to PE, IA bleed 2nd to anticoagulation
Angus DC et al. [29] REMAP-CAP COVID-19	Fixed HC: 50–100 mg qid vs. Shock HC: 50 mg qid vs. No CS (101 pts)		7					1 episode of fungemia in fixed dose HC	1 episode of neuromyopathy in fixed dose HC
Li Y et al. [36]	Median 200 mg/d HC equiv		9 (5–14)					CS: ↑ Secondary infections
Liu J et al. [18]	Not mentioned				Liver injury: CS 18.3% vs. 9.9% no CS (p = 0.001)		myocardial injury: CS 15.6% vs. 10.4% no CS (p = 0.041)		Shock: CS 22% vs. no CS 12.6% (p < 0.001)
Li Q et al. [47]	Pos Prednisone (MP equiv dose 20 mg/d) or iv MP 20–40 mg/d	1–5 after hospital admission	Pos prednisone × 3, iv MP × 3–5					CS in nonsevere COVID-19 pneumonia: ↑ use of antibiotics
Ma Y et al. [48]	CS 56.6 mg (MP equiv) median daily dose		5 median duration					CS: ↑ antibiotic use regardless of disease severity (p < 0.001)
Hu Y et al. [37]	0.75–1 mg/kg/d MP equiv	Median since Sx onset: 7	6 (IQR, 4–8)	No difference					No difference in hypokalemia
Li Y et al. [45]	MP 0.75–1 mg/kg/d × 3 d, then 20 mg × 3 d vs. (no MP and rescue CS)	Early (according to LDH and radiographic progression)	≤7			No difference in psychosis		No difference in secondary infections	No difference in osteoporosis, avascular necrosis
Buetti N et al. [77]	Matched case- control study COVID-19 vs. non-COVID-19 ICU pts							COVID-19 pts:↑ BSI probability, esp after 7 d of ICU admission compared to non-COVID-19 ICU pts (p < 0.00001). COVID-19 pts: significantly ↑ ICU-BSI risk if received anti-IL-1 or anti-IL-6 (sHR 3.20, 95% CI 1.31–7.81, p = 0.011) but not in pts who received CS.
Sterne JAC et al. REACT [23]	Different CS in different schemes								No difference in serious AEs
Van Paassen [25]	Diverse CS strategies		5–10					CS: ↑ use of antibiotics and ↑ secondary infections or sepsis

BC = blood culture, BSI = bloodstream infections, esp = especially, GI = gastrointestinal, ↑ Glu = hyperglycemia, IA = intra-abdominal, PE = pulmonary embolism, and VAP = ventilator- associated pneumonia. CNS=central nervous system; CVS: cardiovascular system.