EBioMedicine (Jun 2023)

Human mesenchymal stem cell therapy in severe COVID-19 patients: 2-year follow-up results of a randomized, double-blind, placebo-controlled trialResearch in context

  • Tian-Tian Li,
  • Bo Zhang,
  • Hui Fang,
  • Ming Shi,
  • Wei-Qi Yao,
  • Yuanyuan Li,
  • Chao Zhang,
  • Jinwen Song,
  • Lei Huang,
  • Zhe Xu,
  • Xin Yuan,
  • Jun-Liang Fu,
  • Cheng Zhen,
  • Yu Zhang,
  • Ze-Rui Wang,
  • Zi-Ying Zhang,
  • Meng-Qi Yuan,
  • Tengyun Dong,
  • Ruidan Bai,
  • Lulu Zhao,
  • Jianming Cai,
  • Jinghui Dong,
  • Jianzeng Zhang,
  • Wei-Fen Xie,
  • Yonggang Li,
  • Lei Shi,
  • Fu-Sheng Wang

Journal volume & issue
Vol. 92
p. 104600

Abstract

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Summary: Background: Long-term effects of human mesenchymal stem cell (MSC) treatment on COVID-19 patients have not been fully characterized. The aim of this study was to evaluate the safety and efficacy of a MSC treatment administered to severe COVID-19 patients enrolled in our previous randomized, double-blind, placebo-controlled clinical trial (NCT 04288102). Methods: A total of 100 patients experiencing severe COVID-19 received either MSC treatment (n = 65, 4 × 107 cells per infusion) or a placebo (n = 35) combined with standard of care on days 0, 3, and 6. Patients were subsequently evaluated 18 and 24 months after treatment to evaluate the long-term safety and efficacy of the MSC treatment. Outcomes measured included: 6-min walking distance (6-MWD), lung imaging, quality of life according to the Short Form 36 questionnaire (SF-36), COVID-19-related symptoms, titers of SARS-CoV-2 neutralizing antibodies, tumor markers, and MSC-related adverse events (AEs). Findings: Two years after treatment, a marginally smaller proportion of patients had a 6-MWD below the lower limit of the normal range in the MSC group than in the placebo group (OR = 0.19, 95% CI: 0.04–0.80, Fisher's exact test, p = 0.015). At month 18, the general health score from the SF-36 was higher in the MSC group than in the placebo group (50.00 vs. 35.00, 95% CI: 0.00–20.00, Wilcoxon rank sum test, p = 0.018). Total severity score of lung imaging and the titer of neutralizing antibodies were similar between the two groups at months 18 and 24. There was no difference in AEs or tumor markers at the 2-year follow-up between the two groups. Interpretation: Long-term safety was observed for the COVID-19 patients who received MSC treatment. However, efficacy of MSC treatment was not significantly sustained through the end of the 2-year follow-up period. Funding: The National Key Research and Development Program of China (2022YFA1105604, 2020YFC0860900, 2022YFC2304401), the specific research fund of The Innovation Platform for Academicians of Hainan Province (YSPTZX202216) and the Fund of National Clinical Center for Infectious Diseases, PLA General Hospital (NCRC-ID202105,413FZT6).

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