Treatment of COVID-19-associated ARDS with mesenchymal stromal cells: a multicenter randomized double-blind trial

SARS-CoV-2-induced ARDS causes high mortality. Umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have potentially relevant immune-modulatory properties, whose place in ARDS treatment is not established. This phase 2b trial was undertaken to assess the efficacy of UC-MSCs in patients with SARS-CoV-2-induced ARDS. Patients were randomly assigned to receive three intravenous infusions of 10⁶ UC-MSCs/kg or placebo (0.9% NaCl) over 5 days after recruitment. For the modified intention-to-treat population, the primary endpoint was the partial pressure of oxygen to fractional inspired oxygen ratio change between baseline (day (D) 0) and D7. PaO₂/FiO₂ changes between D0 and D7 did not differ significantly between the UC-MSCs and placebo groups. Six (28.6%) of the 21 UC-MSCs recipients and six of 24 (25%) placebo-group patients experienced serious adverse events, none of which were related to UC-MSCs treatment. Sub changes for intravenous UC-MSCs-versus placebo-treated adults with SARS-CoV-2-induced ARDS did not differ significantly. Repeated UC-MSCs infusions were not associated with serious adverse events during treatment or after that (until D28). Larger trials enrolling patients earlier during their ARDS are needed to further assess UC-MSCs efficacy in this context.