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Table 1 Published studies of MSC therapy for COVID-19

From: Mesenchymal stem cell-based therapy and exosomes in COVID-19: current trends and prospects

References MSCs' source MSCs' dose and frequency Study type Covid-19 stage Mortality rate in the treatment group versus control group Respiratory outcomes General outcomes Inflammatory markers Diagnostic testing
[57] hUMSCs 5 × 107 cells each time–every three days (day 13–16–19) Case report Treatment group:
Critically ill (1)
Control group:
N/A
(0) in (1) versus N/A The patient was weaned off the ventilator after the second dose of MSCs; denoting an improvement in oxygen saturation An amelioration regarding the vital signs was reported A marked decrease in CRP, AST, ALT, d-dimer, WBCs, neutrophils, and bilirubin levels along with an increase in CD3, CD4, and CD8 T cells after MSCs therapy X-ray: showed GGO
PCR:
Positive for COVID-19
Following MSCs therapy:
CT:
A relief in the GGO was remarkable by the administration of MSCs
(58) NR 1 × 106 cells/Kg- Once Pilot trial Treatment group:
Critically ill (1)
Severe
(4)
Common (2)
Control group:
Severe
(3)
N/A Resolution of dyspnea consistent with an increase in oxygen saturation Resolution of symptoms such as high fever and weakness along with improvement in respiratory rate (in the critically ill patient) Results (of the critically ill patient) displayed a drop in:
CRP, WBCs (including neutrophils along with a rise in lymphocytes) and procalcitonin
Bilirubin and AST
Creatine kinase and troponin
TNF-α
Cytokine storm inflammatory cells: CXCR3 + CD4 + T, CXCR3 + CD8 + T, and CXCR3 + NK
Analysis of transplanted MSCs showed a rise in:
The anti-inflammatory IL-10
The trophic factors: TGF-β, HGF, LIF, GAL, NOA1, FGF, VEGF, EGF, BDNF, and NGF
SPA and SPC indicating a differentiation potential
PCR: Positive for COVID-19
CT (for the critically ill patient): GGO
Following MSCs therapy:
CT (for the critically ill patient):
Obvious reduction in the GGO
PCR: Negative in 4 patients of the treatment group after MSCs therapy
(59) hUMSCs 2 × 106 cells/kg- once Pilot trial Treatment group:
Severe
(12)
Control group:
Severe
(29)
28-day mortality rate:
(0) in (12) versus (3) in (27)
N/A
Only in patients < 65
A rapid improvement of dyspnea (consistent with an improved oxygen status) in the treatment versus control group
Only in patients < 65
A rapid improvement of weakness and fatigue in the treatment versus control group
A significant decline in CRP, IL-6, and a faster improvement of lymphopenia CT: GGO
PCR: Positive
After therapy:
CT:
A reduced inflammatory pattern compared to the control group
(61) UC-MSCs 100 ± 20 × 106 cells
2 doses (day 0 and 3)
A double-blind, phase 1/2a randomized controlled trial Treatment group:
Mild-to-moderate (3)
moderate-to-severe (9)
Control group:
Mild-to-moderate (3)
moderate-to-severe (9)
(2) in (12) versus (7) in (12) by day 28 N/A Administration of UC-MSCs infusions in COVID-19 with ARDS is safe and accompanied with decreased mortality rate and accelerated recovery time
SAEs are improved in UC-MSCs treated group
Survival rate at 28 after UC-MSCs treatment was enhanced (91%), while in control (42%)
Dramatic decrease in inflammatory markers (GM-CSF, IFNγ, IL-5, IL-6, IL-7, TNFα-, TNF-β, PDGF-BB, and RANTES) in UC-MSCs treated group with at day 6 PCR: a insignificant difference in viral load between treatment groups before and after therapy
(60) UC-MSCs 3 × 107 cells per dose
3 doses
(0, 3, and 6) days
Phase 1 clinical trial Treatment group:
Moderate (5), severe (4)
Control group:
Moderate (5), severe (4)
N/A In UC-MSCs treated group, 1 patient needed mechanical ventilation for 1 day, and another suffered from breath shortness. In control group, 4 patients in mechanical ventilation, and 5 had dyspnea No SAEs in UC-MSCs treated group
UC-MSCs
administration in COVID-19 patients was safe and tolerable
Enhancement of percentage of inspired oxygen (PaO2/FiO2) ratio in UC-MSCs group
Decrease in inflammatory cytokines (IFN-γ, TNF-α, MCP-1, IP-10, IL-22, IL-1RA, IL-18, IL-8, and MIP-1) in UC-MSCs treated groups within 2 weeks vs control group PCR: Positive
CT or X-ray: lung lesions showing pneumonia
After therapy:
PCR: Negative
SARS-CoV-2 antibody assay (IgM): Positive in all patients (lower in treatment vs, control group)
CT: disappearance of lung lesions after 2 weeks of UC-MSCs treatment unlike control
(62) UC-MSCs 1 × 108 cells
4 doses (one day interval in between)
Pilot trial Treatment group:
Severe (9)
Critically ill (7)
2 in (16) Improvement of mean oxygenation index from (258) before MSCs infusion to (329) in day 7 of MSCs infusion NR Recovery in lymphocyte counts
The measured cytokines (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and CRP) showed some improvement
CT or X-Ray: GGO
PCR:
SARS-CoV-2 antibody assay: N/A
After therapy:
CTor X-ray: improvement of GGO
PCR:
SARS-CoV-2 antibody assay: N/A
  1. Abbreviation: hUMSCs human umbilical cord mesenchymal stem cells, CRP C-reactive protein, AST aspartate aminotransferase, ALT alanine transaminase, GGO ground-glass opacity, PCR polymerase chain reaction, CT computed tomography, NR not reported, UC-MSCs umbilical cord mesenchymal stem cells, ARDS acute respiratory distress syndrome, SAEs serious adverse events, ELISA enzyme linked immunosorbent, PaO2/FiO2 ratio of arterial oxygen partial pressure to fractional inspired oxygen, ECG electrocardiography