Table 1 The main characteristics of the studies included in the meta-analysis

Guoping Zheng [16]

RCT

66.7 ± 20.4 vs. 69.8 ± 9.1

6/6 vs. 5/6

N = 12 (1:1), adult patients who met the Berlin definition of moderate and severe ARDS

AD MSCs, 1 × 10⁶ cells/kg of body weight, one IV dose

NS

12 (6 vs. 6)

Adverse events

Oxygenation index, length of hospital stay, ventilator-free days and ICU-free days at day 28, and SP-D, IL-6 or IL-8 levels in serum

Michael Matthay [17]

RCT

55 ± 17 vs. 55 ± 20

23/40 vs. 10/20

N = 60 (2:1), ventilated adult patients with moderate-to-severe ARDS

BM-MSCs, 10 × 10⁶ MSC/kg (pbw), one IV dose

Placebo

60 (40 vs. 20)

Infusion-associated adverse events

All-cause mortality, ventilator-free days, intensive-care-free days, days free from organ failure, SOFA score, oxygenation index, and lung injury score

Angiopoietin 2, RAGE, IL-6, or IL-8 levels in serum

Giacomo Lanzoni [18]

RCT

58.58 ± 15.93 vs. 58.83 ± 11.61

5/12 vs. 8/12

N = 24 (1:1), adult patients hospitalized for severe COVID-19

UC-MSCs, 100 ± 20 × 10⁶

UC-MSCs, 2 IV doses

50 mL vehicle solution

24 (12 vs. 12)

Infusion-associated adverse events, cardiac arrest or death within 24 h post-infusion, and incidence of AEs. Survival, time to recovery, and AEs within 31 days

Ismail Dilogo [19]

RCT

–

15/20 vs. 15/20

N = 40 (1:1), intubated patients with severe COVID-19 (moderate and severe ARDS)

UC-MSCs, 1 × 10⁶ cells/kg body weight, one IV dose

100 ml NS

40 (20 vs. 20)

Mortality rate, length of ventilation, Length of ICU stay, AE or serious AE (SAE)

Routine blood count, differential count, CRP, D-dimer, fibrinogen, and procalcitonin, VEGF, ferritin, IL-6, LIF, CX-CR3 in serum

G Adas [33]

RCT

–

–

N = 20 (1:1), COVID-19 patients with severe ARDS

WJ MSCs, 3 × 10⁶ cells/kg body weight, three IV doses

Placebo

20 (10 vs. 10)

Adverse events, mortality, lymphocyte subgroups, and inflammation markers such as CRP, PCT, and Ferritin

Antoine Monsel [34]

RCT

64 ± 10.4 vs. 63.2 ± 11.4

17/21 vs. 20/24

N = 45, COVID-19 patients with ARDS

UC-MSCs, 3 × 10⁶ cells/kg body weight, IV

150 ml NS

45 (21 vs. 24)

Respiratory improvement, SOFA scores, PaO2/FiO2 ratios, ventilation-free days and 28-day mortality; adverse events; and inflammatory biomarkers

Carmen Rebelatto [35]

RCT

53 ± 15.3 vs. 61.7 ± 9.7

8/11 vs. 4/6

N = 17, COVID-19 patients with moderate/severe ARDS

UC-MSCs, 5 × 10⁶ cells/kg body weight, IV

Placebo

17 (11 vs. 6)

Adverse events, mortality, PaO₂/FiO₂; ferritin, IL-6, CRP, D-dimer, and neutrophils

Hamid Aghayan [36]

RCT

62.3 vs. 58.4

6/10 vs. 8/10

N = 20 (1:1), COVID-19 patients with ARDS

PL-MSCs, 1 × 10⁶ cells/kg body weight, IV

Placebo

20 (10 vs. 10)

Adverse events, mortality, and lymphocyte subgroups

Lei Shi [32]

RCT

60.72 ± 9.14 vs. 59.94 ± 7.79

37/65 vs. 19/35

N = 100, COVID-19 patients with ARDS

UC-MSCs, 4 × 10⁶ cells/kg body weight, IV

Placebo

100 (65 vs. 35)

The proportion of whole lung lesion volumes, adverse events, and mortality

Lei Shu [37]

RCT

61.00 ± 17.87 vs. 57.86 ± 15.79

8/12 vs. 16/29

N = 41, COVID-19 patients with ARDS

UC-MSCs, 2 × 10⁶ cells/kg body weight, IV

100 ml NS

41 (12 vs. 29)

Mortality, the time to clinical improvement, adverse events, and lab indexes

Michael Bowdish [38]

RCT

61.8 ± 13.0 vs. 59.6 ± 13.8

79/112 vs. 75/110

N = 222, COVID-19 patients with moderate/severe ARDS

BM-MSCs, 2 × 10⁶ cells/kg body weight, IV

Placebo

222 (112 vs. 110)

Mortality, mechanical ventilation days, clinical improvement, ICU length of stay, and adverse events

Najmeh Farkhad [39]

RCT

–

7/10 vs. 6/10

N = 20, COVID-19 patients with mild/moderate ARDS

UC-MSCs, 1 × 10⁶ cells/kg body weight, IV

Placebo

20 (10 vs. 10)

Mortality, PaO₂/FiO₂, lung imaging, and inflammatory biomarkers such as IL-1 beta, IL-6, and TNF-a

Xiaowei Xu [40]

RCT

58.31 ± 12.49 vs. 61.11 ± 11.03

17/26 vs. 13/18

N = 44, COVID-19 patients with ARDS

UC-MSCs, 9 × 10⁶ cells/kg body weight, IV

Placebo

44 (26 vs. 18)

Mortality, clinical improvement, PaO₂/FiO₂, inflammatory indices (including CRP and IL-6), and adverse events