Human mesenchymal stem cells treatment for severe COVID-19: 1-year follow-up results of a randomized, double-blind, placebo-controlled trial
Lei Shi, Xin Yuan, Weiqi Yao, Siyu Wang, Chao Zhang, Bo Zhang, Jinwen Song, Lei Huang, Zhe Xu, Jun-Liang Fu, Yuanyuan Li, Ruonan Xu, Tian-Tian Li, Jinghui Dong, Jianming Cai, Genshi Li, Yunbo Xie, Ming Shi, Yonggang Li, Yu Zhang, Wei-Fen Xie, Fu-Sheng Wang, Lei Shi, Xin Yuan, Weiqi Yao, Siyu Wang, Chao Zhang, Bo Zhang, Jinwen Song, Lei Huang, Zhe Xu, Jun-Liang Fu, Yuanyuan Li, Ruonan Xu, Tian-Tian Li, Jinghui Dong, Jianming Cai, Genshi Li, Yunbo Xie, Ming Shi, Yonggang Li, Yu Zhang, Wei-Fen Xie, Fu-Sheng Wang
Abstract
Background: The long-term consequences of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment for COVID-19 patients are yet to be reported. This study assessed the 1-year outcomes in patients with severe COVID-19, who were recruited in our previous UC-MSC clinical trial.
Methods: In this prospective, longitudinal, cohort study, 100 patients enrolled in our phase 2 trial were prospectively followed up at 3-month intervals for 1 year to evaluate the long-term safety and effectiveness of UC-MSC treatment. The primary endpoint was an altered proportion of whole-lung lesion volumes measured by high-resolution CT. Other imaging outcomes, 6 min walking distance (6-MWD), lung function, plasma biomarkers, and adverse events were also recorded and analyzed. This trial was registered with ClinicalTrials.gov (NCT04288102).
Findings: MSC administration improved in whole-lung lesion volume compared with the placebo with a difference of -10.8% (95% CI: -20.7%, -1.5%, p = 0.030) on day 10. MSC also reduced the proportion of solid component lesion volume compared with the placebo at each follow-up point. More interestingly, 17.9% (10/56) of patients in the MSC group had normal CT images at month 12, but none in the placebo group (p = 0.013). The incidence of symptoms was lower in the MSC group than in the placebo group at each follow-up time. Neutralizing antibodies were all positive, with a similar median inhibition rate (61.6% vs. 67.6%) in both groups at month 12. No difference in adverse events at the 1-year follow-up and tumor markers at month 12 were observed between the two groups.
Interpretation: UC-MSC administration achieves a long-term benefit in the recovery of lung lesions and symptoms in COVID-19 patients.
Funding: The National Key R&D Program of China, the Innovation Groups of the National Natural Science Foundation of China, and the National Science and Technology Major Project.
Keywords: 1-year follow-up results; COVID-19; Mesenchymal stem cells treatment; RCT.
Conflict of interest statement
Declaration of interests YZ is a current employee of Vcanbio Cell & Gene Engineering Co., Ltd. All authors declare no competing interests.
Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.
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Source: PubMed