Mesenchymal Stem/Stromal Cells: HUMAN MESENCHYMAL STEM CELL THERAPY IN SEVERE COVID-19 PATIENTS: 2-YEAR FOLLOW-UP RESULTS OF A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL

ABSTRACT

Background & Aim: The 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 a randomized, double-blind, placebo-controlled clinical trial (NCT 04288102). Methods, Results & Conclusion(s) A total of 100 patients experiencing severe COVID-19 received either MSC treatment (n = 65, 4x107 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. The outcomes measured included 6-minute walking distance (6-MWD), lung imaging, quality of life according to the Short Form 36 questionnaire, COVID-19-related symptoms, titers of SARS-CoV-2 neutralizing antibodies, MSC-related adverse events (AEs), and tumor markers. 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). On the SF-36 questionnaire, a marginally higher general health score was received by the MSC group at month 18 compared with the placebo group (50.00 vs. 35.00;95% CI 0.00-20.00, Wilcoxon rank sum test, p = 0.016). In contrast, there were no differences in the total severity score of lung imaging or the titer of neutralizing antibodies between the two groups. Meanwhile, there were no MSC-related AEs reported at the 18- or 24-month follow-ups. The serum levels of most of the tumor markers examined remained within normal ranges and were similar between the MSC and placebo groups. Long-term safety was observed for the COVID-19 patients who received MSC treatment. Yet few sustained efficacy of MSC treatment was observed at the end of the 2-year follow-up period. Funding(s) The National Key Research and Development Program of China (2022YFA1105604, 2020YFC0860900), 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 (NCRCID202105,413FZT6). [Figure presented]Copyright © 2023 International Society for Cell & Gene Therapy