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.
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.
Drug: Oseltamivir
Oseltamivir capsules
Drug: hormones
a moderate amount of hormone
Device: oxygen therapy
oxygen therapy,mechanical ventilation and other supportive therapies
Procedure: mesenchymal stem cells
mesenchymal stem cells
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
Fuzhou General Hospital
Fuzhou, Fujian, China
Jianming Tan Tan, M.D and Ph.D, Study Chair
Fuzhou General Hospital