Immunomodulatory therapy for the management of critically ill patients with COVID-19: A narrative review

Table 5 Summary of randomized clinical trials and observational studies including critically ill patients addressing intravenous immunoglobulin and hyperimmune immunoglobulin on coronavirus disease 2019

Ref.	Patients	Intervention	Comparison	Outcome
Xie et al[193], observational	Severe/critical pneumonia and. Lymphocyte count < 0.5 × 109/L (18.9% on MV, 13.8% on NIV/HFNC)	IVIG (20 g/d)	> 48 h after admission (n = 28) vs < 48 h after admission (n = 30)	Reduction in 28-d mortality (23% vs 57%, P = 0.009), need for MV (6.67% vs 32.14%, P = 0.001) and LOS (11.5 ± 1.0 vs 16.9 ± 1.6 d, P = 0.005) in the < 48 h group
Tabarsi et al[194], RCT	Severe pneumonia (36.9% on MV, 78.6% ICU-admitted)	IVIG (400 mg/kg/24 h for 3 d) (n = 52)	Standard care (n = 32)	No difference in mortality (46.1% vs 43.7%, P = 0.83), need for MV (40.4% vs 31.2%, P = 0.39) or ICU admission (75% vs 84.4 %, P = 0.3)
Gharebaghi et al[195], RCT	Severe pneumonia with persisting symptoms or need for supplementary oxygen to maintain SaO2 > 90% after 48 h of treatment	IVIG (20 g daily for three days) (n = 30)	Standard care (n = 29)	Lower in-hospital mortality (20% vs 48.3%, P = 0.022). Mortality. IVIG: OR = 0.003 (95%CI: 0.001-0.815, P = 0.042)
Agarwal et al[200], RCT	Moderate pneumonia	Convalescent plasma (200 mL, 2 doses) (n = 235)	Standard care (n = 229)	Disease progression or mortality: No difference
Li et al[201], RCT	Severe/critical pneumonia (NIV/HFNO: 42.7%, MV/ECMO: 24.3%)	Convalescent plasma (4-13 mL/kg) (n = 52)	Standard care (n = 51)	No improvement in time to clinical improvement within 28 d

RCT: Randomized clinical trial; MV: Mechanical ventilation; NIV: Non-invasive ventilation; LOS: Length of stay; HNFO: High nasal flow oxygen therapy; ICU: Intensive care unit; OR: Odds ratio; IVIG: Intravenous immunoglobulin; ECMO: Extracorporeal membrane oxygenation; CI: Confidence interval.