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.
【저자키워드】 COVID-19, RCT, 1-year follow-up results, Mesenchymal stem cells treatment, RCT., 【초록키워드】 Treatment, clinical trial, Biomarkers, Trial, severe COVID-19, antibody, technology, Symptom, outcome, cohort study, China, outcomes, Lung function, adverse event, Patient, Program, Effectiveness, plasma, Placebo, Follow-up, incidence, group, Other, mesenchymal stem cell, COVID-19 patients, phase 2 trial, administration, primary endpoint, Innovation, MSC, lung lesion, Science, Major, Volume, natural, two groups, foundation, Registered, follow-up time, positive, benefit, Cell, consequence, High-resolution CT, tumor marker, walking distance, enrolled, analyzed, evaluate, proportion, recruited, reported, reduced, median, interval, recorded, in both group, the placebo group, treatment for COVID-19, UC-MSC, umbilical, 【제목키워드】 Treatment, Human, Randomized, placebo-controlled trial, Follow-up, double-blind, stem cell,