Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study
Fermín Sánchez-Guijo (a, b, c, 1), Mariano García-Arranz (b, d, e, 1), Miriam López-Parra (a, b, c, 1), Pablo Monedero (f), Carmen Mata-Martínez (g), Arnoldo Santos (h, i), Víctor Sagredo (j), José-Manuel Álvarez-Avello (f), José Eugenio Guerrero (g), César Pérez-Calvo (h), Miguel-Vicente Sánchez-Hernández (k), José Luis Del-Pozo (l), Enrique J.Andreu (b, m), María-Eugenia Fernández-Santos (b, g, s), Barbara Soria-Juan (d), Luis M.Hernández-Blasco (n), Etelvina Andreu (n), José M.Sempere (o), Agustín G. Zapata (b, q), José M. Moraleda (b, c, r), Bernat Soria (n, p), Francisco Fernández-Avilés (b, g, s, t), Damián García-Olmo (b, d, e, u, 1), Felipe Prósper (b, c, m, 1)
(a) Cell Therapy Area, Hematology Department, IBSAL-Hospital Universitario de Salamanca, Universidad de Salamanca, Salamanca, Spain
(b) RETIC TerCel, ISCIII, Madrid, Spain
(c) Grupo Español de Trasplante y Terapia Celular (GETH), Spain
(d) New Therapies Unit, Health Research Institute Fundación Jiménez Díaz, Madrid, Spain
(e) Surgery Department. School of Medicine, Universidad Autónoma de Madrid, Madrid, Spain
(f) Department of Anesthesia and Intensive Care, Clínica Universidad de Navarra, Pamplona, Spain
(g) Instituto de Investigación Sanitaria (IiSGM), Hospital General Universitario Gregorio Marañón, Madrid, Spain
(h) Intensive Care Unit, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
(i) CIBER de Enfermedades Respiratorias CIBERES, Madrid, Spain
(j) Intensive Care Unit, IBSAL- Hospital Universitario de Salamanca, University of Salamanca, Salamanca, Spain
(k) Department of Anesthesia, IBSAL- Hospital Universitario de Salamanca, University of Salamanca, Salamanca, Spain
(l) Infectious Diseases Division, Microbiology Department, Clínica Universidad de Navarra, Spain
(m) Cell Therapy Area and Hematology Department, Clínica Universidad de Navarra, Pamplona, Spain
(n) Hospital General Universitario de Alicante (Universidad Miguel Hernandez-ISABIAL), Alicante, Spain
(o) Hospital General Universitario de Alicante (Departamento de Biotecnología, Universidad de Alicante-ISABIAL), Alicante, Spain
(p) Institute of Bioengineering, Universidad Miguel Hernández, Alicante, Spain
(q) Department of Cell Biology, Universidad Complutense, Madrid, Spain
(r) Servicio de Hematología, Hospital Clinico Universitario Virgen de la Arrixaca, IMIB, Universidad de Murcia, Murcia, Spain
(s) CIBER Cardiovascular (CIBERCV), Instituto de Salud Carlos III, Madrid, Spain
(t) Department of Medicine, Universidad Complutense, Madrid, Spain
(u) Department of Surgery, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
Identification of effective treatments in severe cases of COVID-19 requiring mechanical ventilation represents an unmet medical need. Our aim was to determine whether the administration of adipose-tissue derived mesenchymal stromal cells (AT-MSC) is safe and potentially useful in these patients.
Thirteen COVID-19 adult patients under invasive mechanical ventilation who had received previous antiviral and/or anti-inflammatory treatments (including steroids, lopinavir/ritonavir, hydroxychloroquine and/or tocilizumab, among others) were treated with allogeneic AT-MSC.
Ten patients received two doses, with the second dose administered a median of 3 days (interquartile range-IQR- 1 day) after the first one. Two patients received a single dose and another patient received 3 doses. Median number of cells per dose was 0.98 × 106 (IQR 0.50 × 106) AT-MSC/kg of recipient's body weight.
Potential adverse effects related to cell infusion and clinical outcome were assessed. Additional parameters analyzed included changes in imaging, analytical and inflammatory parameters.
First dose of AT-MSC was administered at a median of 7 days (IQR 12 days) after mechanical ventilation. No adverse events were related to cell therapy. With a median follow-up of 16 days (IQR 9 days) after the first dose, clinical improvement was observed in nine patients (70%).
Seven patients were extubated and discharged from ICU while four patients remained intubated (two with an improvement in their ventilatory and radiological parameters and two in stable condition). Two patients died (one due to massive gastrointestinal bleeding unrelated to MSC therapy).
Treatment with AT-MSC was followed by a decrease in inflammatory parameters (reduction in C-reactive protein, IL-6, ferritin, LDH and d-dimer) as well as an increase in lymphocytes, particularly in those patients with clinical improvement.
Treatment with intravenous administration of AT-MSC in 13 severe COVID-19 pneumonia under mechanical ventilation in a small case series did not induce significant adverse events and was followed by clinical and biological improvement in most subjects.
CITA DEL ARTÍCULO EClinicalMedicine https://doi.org/10.1016/j.eclinm.2020.100454