TABLE 1.

Main studies on IVIg treatment in COVID‐19 disease

	IVIg dose and duration	Other therapies	Primary outcome in IVIg treated vs controls
Sakoulas et al, 69 2020 USA (open‐label RCT in 16 IVIg treated vs 17 controls)	0.5 g/kg/day for 3 days	Glucocorticoids, antivirals, convalescent plasma	Lower rate of progression to mechanical ventilation, shorter hospital and ICU stay, and greater improvement in PaO2/FiO2. ↓ ferritin and IL‐6
Xie et al, 63 2020 China (single centre retrospective in 58 IVIg treated)	20 g/day for 2‐5 days	Glucocorticoids, antiviral, antibiotic	If IVIg started <48 h of admission, improved pulmonary function, reduced days in hospital/ ICU and improved 28‐day mortality
Herth et al, 80 2020 USA and Germany (multicentre retrospective in 12 IVIg treated)	0.5‐2 g/kg/day in 1‐4 days	Glucocorticoids, antiviral, antibiotic, tocilizumab in 2 pts	If started <4 day of admission, improved pulmonary function reduced hospital and ICU stay
Shao et al, 62 2020 China (multicentre retrospective in 174 IVIg treated vs 151 controls)	0.1‐0.5 g/kg/day for 5‐15 days	Glucocorticoids, antivirals, antibiotics	Improved organ functions. If IVIg given ≤7 days at >15 g per day, reduced 60‐day mortality and ↓ CRP and ↓IL‐6
Gharebaghi et al, 74 2020 Iran (RCT in 30 IVIg treated vs 29 controls)	20 g/day for 3 days		Reduced mortality confirmed at the multivariate regression analysis
Zhou et al, 66 2020 China (single centre retrospective in 40 IVIg treated)	10‐20 g/day for 4‐26 days	Glucocorticoids, antivirals, antibiotics, interferon	Improved oxygenation index and pulmonary lesions with reduced mortality. ↓CRP and ↓ CK
Cao et al, 67 2021 China (multicentre retrospective study in 26 IVIg treated vs controls)	2 g/kg in 2‐5 days plus SoC <2 weeks of disease onset	Standard of care	Lower 28‐day mortality rate. Normalization of IL‐6, IL‐10 and ferritin
Esen et al, 70 2021 Turkey (single centre retrospective in 51 IVIg treated vs 42 controls)	30 g/day for 5 days	IVIg and /or SoC: glucocorticoids, hydroxychloroquine, antivirals, antibiotics, Tocilizumab or anakinra depending on inflammatory markers, vitamin C	Improved ICU survival in IVIg (61%) vs controls (38%) (68 vs 18 days). ↓CRP. No differences in procalcitonin, IL‐6 or D‐dimer
Zantah et al, 71 2020 USA (single centre retrospective in 51 IVIg treated vs 33 controls)	0.5 g/kg/day for 5 days	Glucocorticoids, Anakinra vs Tocilizumab	In both groups: improved clinical outcome, reduced days in ICU. ↓ ferritin and ↓ LDH in living pts
Tabarsi et al, 72 2021 Iran (RCT in 52 IVIg treated vs 32 controls)	0.4 g/kg/day for 3 days	Hydroxychloroquine, antivirals, supportive care	No differences in mortality rate and need of mechanical ventilation
Hou et al, 73 2021 China (single centre retrospective cohort study in 47 IVIg treated vs 66 controls)	0.5‐2 g/kg/day	Glucocorticoids	Reduced mortality and use of mechanical ventilation (25.5% vs 7.6%, P <.008)
Liu et al, 76 2021 China (multicentre retrospective study in severe and non‐severe patients (421 IVIg vs 429 controls)	Median IVIg dose 9.85 g/day for survivors and 10.42 g/day for non‐survivors with a median duration of 9.5 days for all patients	Glucocorticoids, antivirals	No differences in 28‐day mortality and Covid‐19‐related complications
Huang et al, 78 2021 China (retrospective study in non‐severe 45 IVIg treated vs 90 controls)	10 g/day for 3 days in 8 patients; 10 g/day for 5 days in 13 patients; 20 g/day for 3days in 16 patients; 20 g/day for 5 days in 8 patients	Glucocorticoids, hydroxychloroquine, lopinavir/ritonavir, Chinese medicine, thymosin α, arbidol	No benefit from IVIg vs SoC in mortality rate, progression to severe disease, duration of fever, virus clearance time, length of hospital stay, use of antibiotics
Raman et al, 79 2021 India (open‐label multicentre randomized study in non‐severe patients 47 IVIg treated vs 49 controls)	0.4 g/kg/day for 5 days plus SoC:	Antibiotics and lopinavir/ritonavir	Reduced use of mechanical ventilation, hospital and ICU stay. Reduced days to clinical improvement