Treatment with mesenchymal stromal cells (MSCs) is safe and may significantly reduce mortality in patients with severe or critical COVID-19, regardless of whether 1 to 3 doses are used. MSC treatment may also improve pulmonary function, decrease inflammatory cytokines, and lower resource utilization. These were among the findings of a systematic review and meta-analysis published in the journal eClinicalMedicine.
The researchers sought to better understand the safety and efficacy of MSCs in the treatment of severely ill and critically ill patients with COVID-19. To accomplish this, the investigators conducted a systemic review and meta-analysis that included original comparative studies on MSC treatment plus standard therapy for patients who were severely/critically ill with COVID-19. Mortality rates among these patients were compared with those of a control group receiving placebo/standard treatment.
The primary outcomes assessed were in-hospital mortality and adverse events (AEs). The investigators also compared severe vs critical disease and the relative effects of the number of MSC doses (up to 3 total) administered. Additionally, a descriptive analysis was conducted for AEs and secondary study outcomes, including pulmonary function and imaging changes, resource use measured according to length of hospitalization or intensive care unit stay, and change in levels of inflammatory cytokines.
Reviewers searched for original comparative studies, including randomized controlled trials (RCTs), retrospective or prospective cohort studies, and case-control studies conducted through late 2021. A total of 3644 articles were extracted from the literature search, ultimately yielding 13 studies (reported in 14 articles) that met inclusion criteria for data analysis and study quality assessment. The 13 studies selected had sample sizes of between 8 and 210 patients; altogether, they comprised a total of 557 patients.
Results of the analyses showed that treatment with MSCs is associated with a significant benefit in patients with severe/critical COVID-19 with respect to in-hospital mortality (odds ratio [OR], 0.52; 95% CI, 0.32-0.84), with very low heterogeneity observed (P =.998) and fewer AEs. No significant differences in mortality rates were reported between severe COVID-19 (OR, 0.59; 95% CI, 0.29 to 1.18) and critical COVID-19 (OR, 0.56; 95% CI, 0.26 to 1.19). Furthermore, no statistically significant difference was found between the 1-dose MCS therapy group (OR, 0.55; 95% CI, 0.25-1.24), the 2-dose MSC therapy group (OR, 0.47; 95% CI, 0.18-1.24), and the 3-dose MSC therapy group (OR, 0.52; 95% CI, 0.24-1.15).
Limitations of the current analysis included small sample size and variations in both diagnostic guidelines and definitions used to characterize patients with severe/critical COVID-19.
The researchers concluded that MSC therapy appears safe and effective for patients with severe and critical COVID-19, although high-quality, large-scale trials are warranted to confirm this finding.
Yao W, Dong H, Qi J, Zhang Y, Shi L. Safety and efficacy of mesenchymal stem cells in severe/critical patients with COVID-19: a systematic review and meta-analysis. EClinicalMedicine. Published online July 9, 2022. doi:10.1016/j.eclinm.2022.101545