Muscle mass gain and strength recovery after discharge of critical COVID-19 patients treated with mesenchymal stromal cell infusion: a randomized clinical trial

Abstract Background & Aims: During the coronavirus disease 2019 (COVID-19) pandemic, patients with severe infection suffered from profound muscle loss and physical dysfunction. In this context, the immunomodulatory and anti-inflammatory properties of mesenchymal stromal cells (MSCs) could represent a new therapeutic strategy, reducing the impact of post-COVID-19 sequelae. This study aimed to evaluate the influence of MSC infusion on body composition, functionality, and the occurrence and severity of sarcopenia in critically ill COVID-19 patients after hospital discharge, correlating with clinical outcomes, viral load, and pro-inflammatory cytokines. Methods: Prospective, randomized, double-blind, placebo-controlled, phase I/II, single-center study with 16 patients (MSC = 10; placebo = 6) admitted to the Intensive Care Unit (ICU) who received three doses of 5x105 MSCs/kg intravenously. After discharge (at two and four months), the following assessments were applied: anthropometric, body composition by bioelectrical impedance analysis (BIA), and functional tests [handgrip strength (HGS), gait speed (GS), and "Timed Up and Go" (TUG)] to diagnose sarcopenia. Other assessments included cytokine dosages, viral load, laboratory tests (CRP and ferritin), and chest computed tomography (CT) scans. Results: At the end of the four months, nine patients remained in the study (MSC = 5; placebo = 4). Appendicular skeletal muscle mass (p = 0.004), appendicular skeletal muscle index (p = 0.004), phase angle (p = 0.014), and left arm circumference (p = 0.033) showed better results for the MSCs group compared to the placebo group between two and four months. The same occurred for HGS (p = 0.009). TUG (p = 0.039) showed improvement for both groups between two and four months. There was no difference in the diagnosis of sarcopenia between the groups. No correlation was found between cytokine dosage, viral load, CRP, and ferritin in the occurrence of sarcopenia. Myosteatosis was present in most patients. Conclusion: MSCs infusion positively impacted the recovery of muscle mass and strength after severe COVID-19 in patients admitted to the ICU in the critical phase of the disease. Trial registration This clinical trial was registered at the Brazilian Registry of Clinical Trials (ReBEC), UTN code U111112549819, on October 31, 2020 (retrospectively registered) (https//ensaiosclinicos.gov.br/rg/ RBR3fz9 year).