Article (Scientific journals)
Bone Marrow-Derived Mesenchymal Stromal Cell Therapy in Severe COVID-19: Preliminary Results of a Phase I/II Clinical Trial
GREGOIRE, Céline; LAYIOS, Nathalie; LAMBERMONT, Bernard et al.
2022In Frontiers in Immunology, 13, p. 932360
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Keywords :
Immunology; Immunology and Allergy; Mesenchymal stromal cells; Cellular therapy; COVID-19; SARS-CoV-2; Acute respiratory distress syndrome; Intensive care unit; MSC; ARDS; ICU
Abstract :
[en] Background: Treatment of acute respiratory distress syndrome (ARDS) associated with COronaVIrus Disease-2019 (COVID-19) currently relies on dexamethasone and supportive mechanical ventilation, and remains associated with high mortality. Given their ability to limit inflammation, induce immune cells into a regulatory phenotype and stimulate tissue repair, mesenchymal stromal cells (MSCs) represent a promising therapy for severe and critical COVID-19 disease, which is associated with an uncontrolled immune-mediated inflammatory response. Methods: In this phase I-II trial, we aimed to evaluate the safety and efficacy of 3 intravenous infusions of bone marrow (BM)-derived MSCs at 3-day intervals in patients with severe COVID-19. All patients also received dexamethasone and standard supportive therapy. Between June 2020 and September 2021, 8 intensive care unit patients requiring supplemental oxygen (high-flow nasal oxygen in 7 patients, invasive mechanical ventilation in 1 patient) were treated with BM-MSCs. We retrospectively compared the outcomes of these MSC-treated patients with those of 24 matched control patients. Groups were compared by paired statistical tests. Results: MSC infusions were well tolerated, and no adverse effect related to MSC infusions were reported (one patient had an ischemic stroke related to aortic endocarditis). Overall, 3 patients required invasive mechanical ventilation, including one who required extracorporeal membrane oxygenation, but all patients ultimately had a favorable outcome. Survival was significantly higher in the MSC group, both at 28 and 60 days (100% vs 79.2%, p = 0.025 and 100% vs 70.8%, p = 0.0082, respectively), while no significant difference was observed in the need for mechanical ventilation nor in the number of invasive ventilation-free days, high flow nasal oxygenation-free days, oxygen support-free days and ICU-free days. MSC-treated patients also had a significantly lower day-7 D-dimer value compared to control patients (median 821.0 µg/L [IQR 362.0-1305.0] vs 3553 µg/L [IQR 1155.0-6433.5], p = 0.0085). Conclusions: BM-MSC therapy is safe and shows very promising efficacy in severe COVID-19, with a higher survival in our MSC cohort compared to matched control patients. These observations need to be confirmed in a randomized controlled trial designed to demonstrate the efficacy of BM-MSCs in COVID-19 ARDS. Clinical Trial Registration (www.ClinicalTrials.gov), identifier NCT04445454
Disciplines :
Anesthesia & intensive care
Immunology & infectious disease
Cardiovascular & respiratory systems
Author, co-author :
GREGOIRE, Céline   ;  Centre Hospitalier Universitaire de Liège - CHU > > Service d'hématologie clinique
LAYIOS, Nathalie   ;  Centre Hospitalier Universitaire de Liège - CHU > > Service des soins intensifs
LAMBERMONT, Bernard  ;  Centre Hospitalier Universitaire de Liège - CHU > > Service des soins intensifs
LECHANTEUR, Chantal ;  Centre Hospitalier Universitaire de Liège - CHU > > Thérapie cellulaire
BRIQUET, Alexandra ;  Centre Hospitalier Universitaire de Liège - CHU > > Thérapie cellulaire
Bettonville, Virginie ;  Centre Hospitalier Universitaire de Liège - CHU > > Thérapie cellulaire
BAUDOUX, Etienne  ;  Centre Hospitalier Universitaire de Liège - CHU > > Thérapie cellulaire
THYS, Marie ;  Centre Hospitalier Universitaire de Liège - CHU > > Service des informations médico économiques (SIME)
Dardenne, Nadia  ;  Université de Liège - ULiège > Santé publique : de la Biostatistique à la Promotion de la Santé
Misset, Benoît  ;  Centre Hospitalier Universitaire de Liège - CHU > > Service des soins intensifs
BEGUIN, Yves   ;  Centre Hospitalier Universitaire de Liège - CHU > > Service d'hématologie clinique
 These authors have contributed equally to this work.
Language :
English
Title :
Bone Marrow-Derived Mesenchymal Stromal Cell Therapy in Severe COVID-19: Preliminary Results of a Phase I/II Clinical Trial
Publication date :
04 July 2022
Journal title :
Frontiers in Immunology
eISSN :
1664-3224
Publisher :
Frontiers Media SA
Volume :
13
Pages :
932360
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
Fonds Léon Fredericq [BE]
Available on ORBi :
since 08 July 2022

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