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

Abstract

Treatment of severe Coronavirus Disease 2019 (COVID-19) is challenging. We performed a phase 2 trial to assess the efficacy and safety of human umbilical cord-mesenchymal stem cells (UC-MSCs) to treat severe COVID-19 patients with lung damage, based on our phase 1 data. In this randomized, double-blind, and placebo-controlled trial, we recruited 101 severe COVID-19 patients with lung damage. They were randomly assigned at a 2:1 ratio to receive either UC-MSCs (4 × 107 cells per infusion) or placebo on day 0, 3, and 6. The primary endpoint was an altered proportion of whole lung lesion volumes from baseline to day 28. Other imaging outcomes, 6-minute walk test (6-MWT), maximum vital capacity, diffusing capacity, and adverse events were recorded and analyzed. In all, 100 COVID-19 patients were finally received either UC-MSCs (n = 65) or placebo (n = 35). UC-MSCs administration exerted numerical improvement in whole lung lesion volume from baseline to day 28 compared with the placebo (the median difference was -13.31%, 95% CI -29.14%, 2.13%, P = 0.080). UC-MSCs significantly reduced the proportions of solid component lesion volume compared with the placebo (median difference: -15.45%; 95% CI -30.82%, -0.39%; P = 0.043). The 6-MWT 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 in the two groups. These results suggest that 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. (Funded by The National Key R&D Program of China and others. ClinicalTrials.gov number, NCT04288102.

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1

Consort flowchart of the study. ITT intention-to treat population, mITT modified intention-to treat population

Fig. 2

The effect of human umbilical cord-mesenchymal stem cells (UC‑MSCs) on the lung damage in patients with severe COVID-19. UC‑MSCs decreased the proportions of total lung lesion volume and solid component lesion volume compared with the placebo at 28 days. a shows the between-group median difference in the change in total lesion proportion (%) and solid component lesion proportion (%) of the whole lung volume from baseline to day 28. I bars indicate the 95% CI described by Hahn and Meeker (1991). b shows box plots of the change in the total lesion proportion (%) and solid component lesion proportion (%) of the whole lung volume from baseline to day 28. Q1 denotes the first quartile, and Q3 the third quartile. I bars indicate the minimum and maximum. c shows the mean absolute change from baseline in the total lesion proportion (%) and solid component lesion proportion (%) of the whole lung volume. I bars indicate the standard error