Article
Safety and long‑term improvement of mesenchymal stromal cell infusion in critically COVID‑19 patients: a randomized clinical trial
Registro en:
REBELATTO, Carmen Lúcia Kuniyoshi et al. Safety and long‑term improvement of mesenchymal stromal cell infusion in critically COVID‑19 patients: a randomized clinical trial. Stem Cell Research & Therapy, V. 13, n. 122, p. 1–22, 2022
1757-6512
10.1186/s13287-022-02796-1
Autor
Rebelatto, Carmen Lúcia Kuniyoshi
Senegaglia, Alexandra Cristina
Franck, Claudio Luciano
Daga, Debora Regina
Shigunov, Patrícia
Stimamiglio, Marco Augusto
Marsaro, Daniela Boscaro
Schaidt, Bruna
Micosky, Andressa
Azambuja, Ana Paula de
Leitão, Cleverson Alex
Petterle, Ricardo Rasmussen
Jamur, Valderez Ravaglio
Vaz, Isadora May
Mallmann, Antônio Paulo
Carraro Junior, Hipólito
Ditzel, Eduardo
Brofman, Paulo Roberto Slud
Correa, Alejandro
Resumen
COVID-19 is a multisystem disease that presents acute and persistent symptoms, the postacute sequelae (PASC). Long-term symptoms may be due to consequences from organ or tissue injury caused by SARSCoV-2, associated clotting or infammatory processes during acute COVID-19. Various strategies are being chosen by clinicians to prevent severe cases of COVID-19; however, a single treatment would not be efcient in treating such a complex disease. Mesenchymal stromal cells (MSCs) are known for their immunomodulatory properties and regeneration ability; therefore, they are a promising tool for treating disorders involving immune dysregulation and extensive tissue damage, as is the case with COVID-19. This study aimed to assess the safety and explore the long-term efcacy
of three intravenous doses of UC-MSCs (umbilical cord MSCs) as an adjunctive therapy in the recovery and postacute sequelae reduction caused by COVID-19. To our knowledge, this is one of the few reports that presents the longest follow-up after MSC treatment in COVID-19 patients. This was a phase I/II, prospective, single-center, randomized, double-blind, placebo-controlled clinical trial. Seventeen patients diagnosed with COVID-19 who require intensive care surveillance and invasive mechanical ventilation—critically ill patients—were included. The patient infusion was three doses of 5× 105
cells/kg UC-MSCs, with a dosing interval of 48 h (n=11) or placebo (n=6). The evaluations consisted of a clinical assessment, viral load, laboratory testing, including blood count, serologic, biochemical, cell subpopulation, cytokines and CT scan. The results revealed that in the UC-MSC group, there was a reduction in the levels of ferritin, IL-6 and MCP1- CCL2 on the fourteen day. In the second month, a decrease in the levels of reactive C-protein, D-dimer and neutrophils and an increase in the numbers of TCD3, TCD4 and NK lymphocytes were observed. A decrease in extension of lung damage was observed at the fourth month. The improvement in all these parameters was maintained until the end of patient follow-up.