Table 1 Published studies of MSC therapy for COVID-19

[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