| Title | 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 |
| Authors | Shi, Lei Huang, Hai Lu, Xuechun Yan, Xiaoyan Jiang, Xiaojing Xu, Ruonan Wang, Siyu Zhang, Chao Yuan, Xin Xu, Zhe Huang, Lei Fu, Jun-Liang Li, Yuanyuan Zhang, Yu Yao, Wei-Qi Liu, Tianyi Song, Jinwen Sun, Liangliang Yang, Fan Zhang, Xin Zhang, Bo Shi, Ming Meng, Fanping Song, Yanning Yu, Yongpei Wen, Jiqiu Li, Qi Mao, Qing Maeurer, Markus Zumla, Alimuddin Yao, Chen Xie, Wei-Fen Wang, Fu-Sheng |
| Affiliation | Chinese Peoples Liberat Army Gen Hosp, Natl Clin Res Ctr Infect Dis, Dept Infect Dis, Med Ctr 5, Beijing, Peoples R China Wuhan Huoshenshan Hosp, Wuhan, Peoples R China Second Mil Med Univ, Changzheng Hosp, Dept Resp, Shanghai, Peoples R China Maternal & Child Hosp Hubei Prov, Opt Valley Branch, Wuhan, Peoples R China Chinese Peoples Liberat Army Gen Hosp, Dept Hematol, Med Ctr 2, Beijing, Peoples R China Peking Univ First Hosp, Peking Univ, Clin Res Inst, Beijing, Peoples R China Gen Hosp Cent Theater Command, Dept Infect Dis, Wuhan, Peoples R China VCANBIO Cell & Gene Engn Corp Ltd, Tianjin, Peoples R China Natl Ind Base Stem Cell Engn Prod, Tianjin, Peoples R China Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Hematol, Wuhan, Peoples R China Chinese Peoples Liberat Army Gen Hosp, Key Lab Canc Ctr, Med Ctr 5, Beijing, Peoples R China Second Mil Med Univ, Changzheng Hosp, Dept Endocrinol & Metab, Shanghai, Peoples R China Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Radiol, Wuhan, Peoples R China Chinese Peoples Liberat Army Gen Hosp, Nursing Dept, Med Ctr 5, Beijing, Peoples R China Champalimaud Ctr Unknown, Immunotherapy Programme, Lisbon, Portugal Johannes Gutenberg Univ Mainz, Med Clin 1, Mainz, Germany UCL, Ctr Clin Microbiol, Div Infect & Immun, London, England UCL Hosp, NIHR Biomed Res Ctr, London, England Second Mil Med Univ, Changzheng Hosp, Dept Gastroenterol, Shanghai, Peoples R China |
| Issue Date | 10-Feb-2021 |
| Publisher | SIGNAL TRANSDUCTION AND TARGETED THERAPY |
| 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 x 10(7) 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. |
| URI | http://hdl.handle.net/20.500.11897/622172 |
| ISSN | 2095-9907 |
| DOI | 10.1038/s41392-021-00488-5 |
| Indexed | SCI(E) |
| Appears in Collections: | 第一医院 |
