Safety and Effectiveness of Mesenchymal Stem Cells in the Treatment of Pneumonia of Coronavirus Disease 2019

900 Hospital of the People's Liberation Army Joint Logistic Support Force

Status and phase: Unknown; Early Phase 1

Conditions: COVID-19 Pneumonia

Treatments: Device: oxygen therapy; Drug: Oseltamivir; Procedure: mesenchymal stem cells; Drug: hormones

Study type: Interventional

Funder types: Other

Identifiers

NCT04371601

MSC-CoViD-2020

Details and patient eligibility

About

The outbreak of coronavirus disease 2019 (COVID-19) at the end of 2019 has seen numerous patients experiencing severe acute lung injury (ALI), which developed into severe respiratory distress syndrome (ARDS). The mortality was as high as 20% -40%. Due to the lack of effective antiviral treatments, supporting treatment is the predominant therapy for COVID-19 pneumonia. Its cure is essentially dependent on the patient's immunity. While the immune system eliminates the virus, numerous inflammatory cytokines are produced and a cytokine storm occurs in severe cases.

Mesenchymal stem cells (MSCs) play an important role in injury repair and immune regulation, showing advantageous prospects in the treatment of COVID-19 pneumonia. MSCs prevent cytokine storms by retarding the TNF-α pathway, alleviate sepsis by modulating macrophages, neutrophils, NK cells, DC cells, T lymphocytes and B lymphocytes. After infused, MSCs aggregate in the lungs, improve the lung microenvironment, protect alveolar epithelia, and improve pulmonary fibrosis and pulmonary function.

Full description

In vitro, Mesenchymal stem cells were revealed to inhibit the secretion of inflammatory cytokines by spleen lymphocytes and up-regulate regulatory T cells, thereby inhibiting the secretion of interferon-γ(IFN-γ) induced by lymphocytes and Tumor Necrosis Factor(TNF) induced by macrophage.

Animal models and preclinical studies have shown that mesenchymal stem cells (MSCs) were implanted into inflammatory lung tissues after infusion, which significantly improved the clinical manifestations and histopathological lesions caused by acute lung injury. Mesenchymal stem cells inhibited the effects of interleukin-1 (IL-1) through regulatory T cells (CD4 + CD25 + FOXP3 + Treg cells) and by antagonizing the expression interleukin-1 receptor (IL1-RA). Mesenchymal stem cells significantly down-regulated pro-inflammatory factors by inhibiting the expression of IL-1, TNF and IFN-γ in lung tissue, and up-regulated anti-inflammatory factor by enhancing the expression of IL -10 and regulatory T cells, respectively, thereby dampening the inflammatory response.

Enrollment: 60 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• patients with severe COVID-19 pneumonia
• willing to give informed consent

Exclusion criteria

• patients with mild COVID-19 pneumonia
• liver dysfunction
• concomitant with other active infection
• renal dysfunction
• Heart failure >grade 2
• pregnant
• history of COPD

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Control group

Active Comparator group

Description:

conventional symptomatic treatments such as antiviral (oseltamivir), hormones, oxygen therapy, mechanical ventilation and other supportive therapies

Treatment:

Device: oxygen therapy

Drug: Oseltamivir

Drug: hormones

Experimental group

Experimental group

Description:

On the basis of the above-mentioned conventional symptomatic treatment and supportive therapy, umbilical cord mesenchymal stem cells were given at 106/Kg body weight / time, once every 4 days for a total of 4 times. Peripheral intravenous infusion was given within 3 days of first admission

Treatment:

Device: oxygen therapy

Drug: Oseltamivir

Procedure: mesenchymal stem cells

Drug: hormones