Download This Paper
Preprints with The Lancet is a collaboration between The Lancet Group of journals and SSRN to facilitate the open sharing of preprints for early engagement, community comment, and collaboration. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early-stage research papers that have not been peer-reviewed. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. The findings should not be used for clinical or public health decision-making or presented without highlighting these facts. For more information, please see the FAQs.
Human Umbilical Cord-Derived Mesenchymal Stem Cell Treatment for Severe COVID-19: 3-Year Follow-Up of a Randomized, Double Blind, Placebo-Controlled Trial
26 Pages Posted: 17 Jan 2024
More...Abstract
Background: Although a series of clinical trials on human umbilical cord-derived mesenchymal stem cell (UC-MSC) therapy in patients with COVID-19 have been registered and conducted, much attention has been paid to the long-term safety and efficacy of this medication. This study aimed to evaluate the 3-year safety and efficacy in patients with severe COVID-19 receiving mesenchymal stem cell (MSC) treatment (NCT 04288102).
Methods: One hundred patients with severe COVID-19 were randomized to receive either MSC infusion (n = 65, 4 × 10*7 cells/dose, on days 0, 3, and 6) or placebo treatment (n = 35), and both were combined with the standard of care. At 36 months after MSC therapy, the patients were followed up to assess the long-term safety and efficacy. All participants were evaluated using parameters including lung imaging, 6-min walking distance (6-MWD), pulmonary function tests, quality of life according to the 36-Item Short Form Health Survey (SF-36) questionnaire, long-COVID-related symptoms, new-onset comorbidities, tumor markers, and COVID reinfection.
Findings: Three years after treatment, 46.94% (23/49) of patients in the MSC group and 34.48% (10/29) of patients in the placebo group had normal presentation on CT images (OR=1.68, 95% CI: 0.65–4.34). The general health (GH) score from the SF-36 was 67.0 in the MSC group and 50.0 in the placebo group (Difference=12.86, 95% CI: 1.44–24.28). The total severity scores of lung imaging, 6-MWD, pulmonary function test, and long-COVID-related symptoms were similar between the two groups. No differences in new-onset complications (including tumorigenesis) or tumor marker levels were observed between the two groups. After adjustment of the dynamic zero-COVID-19 strategy in China, 53.06% (26/49) of patients in the MSC group and 67.86% (19/28) of patients in the placebo group were reinfected with SARS-CoV-2 (OR=0.54, 95% CI: 0.20–1.41).
Interpretation: Within a 3-year follow-up period, the long-term safety of MSC infusion in patients with severe COVID-19 was well tolerated. MSC administration may have potential benefits in the recovery of lung lesions and symptoms in COVID-19 patients.
Funding: The National Key R&D 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).
Declaration of Interest: WQY, TYD and YZ are current employees of Wuhan Optics Valley Zhongyuan Pharmaceutical Co., Ltd. All authors declare no other conflicts of interest.
Ethical Approval: This study was approved by the Ethics Committee of the Fifth Medical Center of the Chinese PLA General Hospital (Approval No.: 2020-013-D).
Keywords: Keywords：COVID-19, Mesenchymal stem cell Therapy, 3-year follow-up, Long-COVID
Suggested Citation: Suggested Citation