Safety, feasibility, and exploratory biomarker findings of bone marrow-derived mesenchymal stromal cells in hospitalized severe COVID-19: a phase I/II randomized trial.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) is characterized by hypoxemic pneumonia and immune dysregulation. Mesenchymal stromal cells (MSCs) possess immunomodulatory and reparative properties and have emerged as a potential adjunctive therapy. However, evidence regarding the safety and biological effects of bone marrow-derived MSCs in severe COVID-19 remains limited. This study aimed to evaluate the feasibility and early safety of MSC administration and to describe exploratory clinical, imaging, and inflammatory biomarker findings. METHODS: We conducted a single-center, randomized, controlled phase I/II trial in hospitalized adults with severe COVID-19 in The First Affiliated Hospital of Guangzhou Medical University, China. Participants were allocated 1:1 to standard of care alone or standard of care plus a single intravenous infusion of bone marrow-derived MSCs (1×106 cells·kg-1). Outcomes included adverse events (AEs) and serious adverse events (SAEs), bedside clinical parameters, quantitative chest computed tomography (CT) metrics, and longitudinal plasma chemokines. RESULTS: Twenty patients were randomized; however, 12 patients (six per group) withdrew before receiving study treatment and provided no post-randomization outcome data. Consequently, eight patients were included in the safety and evaluable analyses (control n=4; MSC n=4). Baseline characteristics were broadly comparable between groups, with isolated differences in coagulation indices. Bedside clinical parameters remained stable in both groups. Quantitative chest CT metrics generally improved over time in both groups, without clear descriptive separation between groups. MSC infusion was well tolerated, and no AEs were judged to be related to MSC administration. CONCLUSIONS: A single infusion of bone marrow-derived MSCs was safe and feasible in severe COVID-19. These early safety, feasibility, and biomarker observations provide a basis for further evaluation in adequately powered controlled trials with complete longitudinal sampling and clinically meaningful endpoints. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04346368 (registered on 15 April 2020).