Effectiveness and Safety of MSC Cell Therapies for Hospitalized Patients with COVID-19: A Systematic Review and Meta-analysis

Qu, W.; Wang, Z.; Cook, E. E.; Siddik, A. B.; Bu, G.; Allickson, J. G.; Kubrova, E.; Caplan, A. I.; Hare, J. M.; Ricordi, C.; Pepine, C. J.; Kurtzberg, J.; Pascual, J. M.; Mallea, J. M.; Rodriguez, R. L.; Nayfeh, T.; Saadi, S.; Richards, E. M.; March, K.; Sanfilippo, F. P.

ABSTRACT MSC (a.k.a. mesenchymal stem cell or medicinal signaling cell) cell therapies have shown promise in decreasing mortality in ARDS and suggest benefits in treatment of COVID-19 related ARDS. We performed a meta-analysis of published trials assessing the effectiveness and adverse events (AE) of MSC cell therapy in individuals hospitalized for COVID-19. Systematic searches were performed in multiple databases through April 8th, 2021. Reports in all languages including randomized clinical trials (RCTs), comparative observational studies, and case series/case reports were included. Random effects model was used to pool outcomes from RCTs and comparative observational studies. Outcome measures included all-cause mortality, serious adverse events (SAEs), AEs, pulmonary function, laboratory and imaging findings. A total of 413 patients were identified from 25 studies, which included 8 controlled trials (3 RCTs), 5 comparative observational studies, (n=300) and 17 case-series/case reports (n=113). The patients age was 60.5 years (mean), 33.7% were women. When compared with the control group, MSC cell therapy was associated with reduction in all-cause mortality (RR=0.31, 95% CI: 0.12 to 0.75, I2=0.0%; 3 RCTs and 5 comparative observational studies, 300 patients), reduction in SAEs (IRR=0.36, 95% CI: 0.14 to 0.90, I2=0.0%; 3 RCTs and 2 comparative studies, n=219), no significant difference in AE rate. A sub-group with pulmonary function studies suggested improvement in patients receiving MSC. These findings support the potential for MSC cell therapy to decrease all-cause mortality, reduce SAEs, and improve pulmonary function compared to conventional care. Large scale double-blinded, well-powered RCTs should be conducted to further explore these results.