Cellular immunotherapy for COVID-19-induced acute respiratory distress syndrome: Results of the CIRCA-19 phase 1 safety and phase 2 randomized controlled trials

Clinical Snapshot

Key Findings

• P Value: Not reported

• Effect Size: Qualitative improvement in all clinical outcomes (specific measures not quantified)

• Primary Outcome: Safety and tolerability of UC-MSC therapy

• Nnt Or Sensitivity: Not calculable from available data

• Confidence Interval: Not reported

Clinical Application

Limited by requirement for specialized cell culture facilities and expertise in MSC preparation and administration Would require TGA approval for cell therapy products; relevant for Australian ICUs but implementation would need significant infrastructure investment Critically ill patients with severe COVID-19 ARDS in intensive care settings

Abstract

The ability of immunomodulatory mesenchymal stromal cells (MSCs) to improve COVID-19-associated acute respiratory distress syndrome (ARDS) in clinical trials is uncertain. We assessed whether freshly cultured umbilical cord (UC)-derived MSCs improved outcomes in patients with severe COVID-19 ARDS. We enrolled 37 patients with severe COVID-19 ARDS: 15 in the phase 1 dose escalation and open label extension studies (NCT04400032), and 22 patients in the phase 2b randomized clinical trial (NCT04865107). Delivery of up to 270 × 106 MSCs in three divided daily doses was well tolerated and resulted in qualitative improvement in all clinical outcomes. Furthermore, MSCs resulted in resolution of lymphopenia, consistent with an important immunomodulatory effect, with significant improvement in patient reported quality-of-life measures (SF-36) at 6 months pointing to possible durable clinical effects. These findings suggest a potential benefit of freshly cultured, UC-MSCs in severe COVID-19 ARDS, associated with biological evidence of favorable immunomodulatory activity.

References

1. 1.English, S. W., Fergusson, D. A., Lalu, M. M., Courtman, D. W., Khan, S., Sobh, M., Watpool, I., Champagne, J., Hodgins, S., Thébaud, B., Soliman, K., Chassé, M., Dos Santos, C. C., Möbius, M. A., Freund, D., Rüdiger, M., & Stewart, D. J. (2026). Cellular immunotherapy for COVID-19-induced acute respiratory distress syndrome: Results of the CIRCA-19 phase 1 safety and phase 2 randomized controlled trials. *Stem Cell Reports*, *15*(4), 102854. https://doi.org/10.1016/j.stemcr.2026.102854