Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients: a randomised, double-blind, placebo controlled phase 2 trial

Abstract Objective To assess the safety and efficacy of human umbilical cord-derived MSCs (UC-MSCs) for severe COVID-19 patients with lung damage. Design Multicentre, randomised, double-blind, placebo-controlled trial. Setting Two hospitals in Wuhan, China, 5 March 2020 to 28 March 2020. Participants 101 severe COVID-19 patients with lung damage aged between 18–74 years. Intervention Patients were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 107 cells per infusion) or placebo on days 0, 3, and 6. Main outcome measures The primary endpoints were safety and an altered proportion of whole lung lesion size from baseline to day 28, measured by chest computed tomography. Secondary outcomes were reduction of consolidation lesion sizeand lung function improvement (6-minute walk test, maximum vital capacity, diffusing capacity). Primary analysis was done in the modified intention-to-treat (mITT) population and safety analysis was done in all patients who started their assigned treatment. Results 100 patients were finally recruited to receive either UC-MSCs (n = 65) or placebo (n = 35). The patients receiving UC-MSCs exhibited a trend of numerical improvement in whole lung lesion size from baseline to day 28 compared with the placebo cases (the median difference was −13.31%, 95%CI −29.14%, 2.13%, P=0.080). UC-MSCs administration significantly reduced the proportions of consolidation lesion size from baseline to day 28 compared with the placebo (median difference: −15.45%, 95% CI −30.82%, −0.39%, P=0.043). The 6-minute walk test showed an increased distance in patients treated with UC-MSCs (difference: 27.00 m, 95% CI 0.00, 57.00, P=0.057). The incidence of adverse events was similar, and no serious adverse events were observed in the two groups. Conclusions UC-MSCs treatment is a safe and potentially effective therapeutic approach for COVID-19 patients with lung damage. A phase 3 trial is required to evaluate effects on reducing mortality and preventing long-term pulmonary disability. Trial registration ClinicalTrials.gov Identifier: NCT04288102 Key Points Question Are human umbilical cord-derived mesenchymal stem cells (UC-MSCs) safe and effective therapeutic option for limiting lung damage in severe coronavirus disease 2019 (COVID-19)? Finding In this randomised, double-blind, placebo-controlled, phase 2 trial that included 100 COVID-19 patients with lung damage, human UC-MSCs medication showed a trend of improvement in whole lung lesion size and significantly reduced the proportions of consolidation lesions from baseline to day 28 in the treated patients compared with the placebo subjects. The 6-minute walk test showed a longer distance in UC-MSCs than placebo group but without significantly difference. UC-MSCs delivery was well tolerated, with no serious adverse events. Meaning Human UC-MSC administration for hospitalized COVID-19 with lung damage is safe. Treatment with human UC-MSC improves the resolution of lung lesions, particularly the consolidation lesions.