Treatment of severe COVID-19 with human umbilical cord mesenchymal stem cells

Lei Shu, Changming Niu, Ruyou Li, Tingrong Huang, Yan Wang, Mao Huang, Ningfei Ji, You Zheng, Xiaolin Chen, Lei Shi, Mingjing Wu, Kaili Deng, Jing Wei, Xueli Wang, Yang Cao, Jiaxin Yan, Ganzhu Feng, Lei Shu, Changming Niu, Ruyou Li, Tingrong Huang, Yan Wang, Mao Huang, Ningfei Ji, You Zheng, Xiaolin Chen, Lei Shi, Mingjing Wu, Kaili Deng, Jing Wei, Xueli Wang, Yang Cao, Jiaxin Yan, Ganzhu Feng

Abstract

Background: COVID-19 is a highly infectious respiratory disease. No therapeutics have yet been proven effective for treating severe COVID-19.

Objectives: To determine whether human umbilical cord mesenchymal stem cell infusion may be effective and safe for the treatment of severe COVID-19.

Methods: Patients with severe COVID-19 were randomly divided into 2 groups: the standard treatment group and the standard treatment plus hUC-MSC infusion group. The incidence of progression from severe to critical illness, 28-day mortality, clinical symptom improvement, time to clinical symptom improvement, hematologic indicators including C-reactive protein, lymphocyte number, and interleukin 6, and imaging changes were observed and compared between the two groups.

Measurements and main results: The incidence of progression from severe to critical illness and the 28-day mortality rate were 0 in the hUC-MSC treatment group, while 4 patients in the control group deteriorated to critical condition and received invasive ventilation; 3 of them died, and the 28-day mortality rate was 10.34%. In the hUC-MSC treatment group, the time to clinical improvement was shorter than that in the control group. Clinical symptoms of weakness and fatigue, shortness of breath, and low oxygen saturation obviously improved beginning on the third day of stem cell infusion and reached a significant difference on day 7. CRP and IL-6 levels were significantly lower from day 3 of infusion, the time for the lymphocyte count to return to the normal range was significantly faster, and lung inflammation absorption was significantly shorter on CT imaging in the hUC-MSC group than in the control group.

Conclusions: Intravenous transplantation of hUC-MSCs is a safe and effective method that can be considered a salvage and priority treatment option for severe COVID-19.

Trial registration: Chinese Clinical Trial Registration; ChiCTR2000031494; Registered on 2 April 2020; http:// www.medresman.org.

Keywords: Clinical characteristics; Coronavirus disease-19 (COVID-19); Coronavirus pneumonia; Human umbilical cord mesenchymal stem cells.

Conflict of interest statement

Lei Shu, Changming Niu, Ruyou Li, Tingrong Huang, Yan Wang, Mao Huang, Ningfei Ji, You Zheng, Xiaolin Chen, Lei Shi, Mingjing Wu, Kaili Deng, Jing Wei, Xueli Wang, Yang Cao, Jiaxin Yan, and Ganzhu Feng declared that there were no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram of the clinical trial in this study. Abbreviations: UC-MSCs, umbilical cord mesenchymal stem cells; COVID-19, coronavirus disease 2019
Fig. 2
Fig. 2
The dynamic changes in CRP, IL-6, oxygenation index, and lymphocyte number in patients in the hUC-MSC and control groups. (**P < 0.01, ***P < 0.001)
Fig. 3
Fig. 3
Chest computed tomography (CT) images of the patients in the hUC-MSC and control groups. CT imaging results for 6 patients (P3, P5, and P11 indicate patients 3, 5, and 11 from the hu-MSC group; P16, P23, and P37 indicate patients 16, 23, and 37 from the control group) at 3 time points (pretreatment, 1 week after treatment, and 2 weeks after treatment). The red arrows show the sites of inflammatory exudation, consolidation, or absorption. The red triangles show the sites of Crazy-paving pattern; the yellow triangles show the sites of consolidation; the blue triangles show the sites of GGO; the black triangles show the sites interlobular septal thickening; the purple triangles show the sites of bronchial wall thickening

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