Umbilical cord mesenchymal stromal cells for respiratory complications of COVID-19 infection (ProTrans): phase II randomized clinical trial.

Publication date: Jul 01, 2026

Severe COVID-19 is characterized by an aberrant immune response leading to systemic inflammation, organ dysfunction and high mortality among hospitalized patients. Mesenchymal stromal cells (MSCs), due to their immunomodulatory and tissue-reparative properties, are a potential therapeutic option. This study evaluated the safety of Wharton’s Jelly-derived MSCs (WJ-MSCs) in patients with severe COVID-19 pneumonia. ProTrans19+ is a phase II, randomized, double-blind, placebo-controlled trial. Adults hospitalized with severe COVID-19 pneumonia (i. e., patients requiring either >4L/min of supplemental oxygen, and/or noninvasive ventilation and/or high-flow oxygen therapy to achieve arterial oxygen saturation >96%) were randomized 1:1 to receive a single intravenous infusion of 100 cD7 10⁶ WJ-MSCs (ProTrans) or placebo. The primary endpoint was a composite of death or requirement for invasive mechanical ventilation within 15 days after intervention. Secondary endpoints included changes in clinical status, time to improvement, hospital and ICU length of stay and safety outcomes. Bayesian and frequentist methods were used for statistical analysis. Between 2021 and 2023, 1519 COVID patients were screened, 46 were eligible and 19 subjects were randomized (WJ-MSC, n = 9; placebo, n = 10). Due to slow accrual and evolving pandemic dynamics, the trial was terminated early after enrolment of 19 participants. The infusion was well tolerated, with only grade 1 adverse events reported in both groups. One WJ-MSC recipient died, but the DSMB deemed the event unrelated to the intervention. The estimated primary event rate was 11% (95% CI: 0-48%) in the WJ-MSC arm and 0% (95% CI: 0-31%) in the placebo arm. The posterior probability of achieving a ≥20% absolute risk reduction in the primary event rate in favor of WJ-MSC was 0. 7%. No significant differences were observed in secondary outcomes. The administration of WJ-MSCs was safe in multi-morbid patients with severe COVID-19 pneumonia receiving multiple concomitant therapies. The small sample size precludes efficacy conclusions. The study highlights the logistical and methodological challenges of conducting advanced therapy trials during a rapidly evolving pandemic and the need for context-sensitive designs.

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