Mesenchymal stromal cell therapy for COVID-19 acute respiratory distress syndrome: A double-blind randomised controlled trial

Mesenchymal stromal cells (MSC) have immunomodulatory and tissue-regenerative properties and have shown promising results in acute respiratory distress syndrome (ARDS) of multiple causes, including COVID-19. We conducted a randomised (1:1), placebo-controlled, double-blind clinical trial to assess the efficacy and safety of one bone marrow-derived MSC infusion in patients with moderate to severe ARDS caused by COVID-19. The primary endpoint was change in the PaO2/FiO2 ratio from baseline to day 7. Key secondary endpoints included clinical improvement in the WHO 7-point ordinal scale and safety variables. Twenty patients were included. Clinical improvement at day 7 was greater in the MSC group than in the control (5, 50% vs 0, 0%). Median time to discontinuation of supplemental oxygen was also shorter (14 [IQR 10-18] vs. 23 [IQR 19.5-25] days), resulting in shorter hospital length of stay (17.5 [IQR 11-28] vs. 28 [IQR 26-28] days). PaO2/FiO2 increase from baseline to day 7 was 83.3 in the MSC group vs. 57.6 in the control group. No infusion-related or treatment-related serious adverse events occurred during the one-year follow-up. MSC therapy is safe in moderate to severe COVID-19 ARDS and may be beneficial, even in a context of low mortality, accelerating clinical recovery and hospital discharge. Trial Registration EudraCT Number: 2020-002193-27, registered on July 14th, 2020, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-002193-27/ES. NCT number: NCT04615429, registered on November 4th, 2020, https://clinicaltrials.gov/ct2/show/NCT04615429.