Efficacy and Safety of Human Umbilical Cord-derived Mesenchymal Stem Cells for COVID-19 Pneumonia: a Meta-analysis of Randomized Controlled Trials

Background: Elevated levels of inflammatory factors are associated with poor prognosis in coronavirus disease-19 (COVID-19). However, mesenchymal stem cells (MSCs) have immunomodulatory functions. Accordingly, this meta-analysis aimed to determine the efficacy and safety of MSC-based therapy in patients with COVID-19 pneumonia.

Methods: Online global databases were used to find relevant studies. Two independent researchers then selected and evaluated the studies for suitability while the Cochrane risk of bias tool determined the quality of all articles and Cochran's Q test and I index assessed the degree of heterogeneity in the principal studies. Statistical analysis was performed using Review Manager software, and the effect of each study on the overall estimate was evaluated by sensitivity analysis.

Results: Seven studies were included in the meta-analysis, and all MSCs used in the trials were acquired from the umbilical cord. The results of these studies (n = 328) indicated that patients with COVID-19 pneumonia who received MSCs had a 0.58 risk of death compared with controls (95% CI = 0.38, 0.87; P = 0.53; I = 0%). In terms of inflammatory biomarkers, MSCs reduced the levels of C-reactive protein (n = 88; MD =  - 32.49; 95% CI =  - 48.43, - 16.56; P = 0.46; I = 0%) and interferon-gamma (n = 44; SMD =  - 1.23; 95% CI =  - 1.89, - 0.57; P = 0.37; I = 0%) in severe COVID-19 patients but had no significant effect on interleukin-6 (n = 185; MD =  - 0.75; 95% CI =  - 7.76, 6.27; P = 0.57; I = 0%). A summary of the data revealed no significant differences in adverse events (n = 287) or serious adverse events (n = 229) between the MSC and control groups.

Conclusions: Infusion of umbilical cord-derived MSCs is an effective strategy for treating patients with COVID-19 pneumonia, with no noticeable adverse effects.