Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study

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Sánchez Guijo, Fermín and García Arranz, Mariano and López-Parra, Miriam and Monedero, Pablo and Mata-Martínez, Carmen and Santos, Arnoldo and Sagredo, Víctor and Álvarez-Avello, José-Manuel and Guerrero, José Eugenio and Pérez-Calvo, César and Sánchez Hernández, Miguel Vicente and Del-Pozo, José Luis and Andreu, Enrique J. and Fernández-Santos, María-Eugenia and Soria-Juan, Bárbara and Hernández-Blas, Luis-M. and Andreu, Etelvina and Sempere, José M. and Zapata, Agustín M. and Moraleda, Jose María and Soria, Bernat and Fernández-Avilés, Francisco and García-Olmo, Damián and Prósper, Felipe (2020) Adipose-derived mesenchymal stromal cells for the treatment of patients with severe SARS-CoV-2 pneumonia requiring mechanical ventilation. A proof of concept study. EClinicalMedicine, 25 (100454). pp. 1-9. ISSN 2589-5370

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Abstract

Background
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.

Methods
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.

Findings
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.

Interpretation
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.

Resumen (otros idiomas)

El manuscrito es un report sobre el tratamiento de 13 pacientes con Covid-19 severo (todos con ventilación mecánica invasiva) que habían previamente recibido sin resultado los tratamientos convencionales (esteroides, lopinavir/ritonavir, hidroxicloroquina y/o tocilizumab, etc...), mediante la inyección intravascular de MSC adiposas alogénicas. Diez pacientes recibieron dos dosis, otros dos solo una y un tercero, tres. Aparte de evaluar posibles efectos adversos y la evolución de la enfermedad se estudiaron distintos parámetros analíticos, inflamatorios e inmunológicos. No se observaron efectos adversos debido a la vía de inyección, muy importante para la viabilidad de las MSC y su funcionamiento; no obstante, el tratamiento podría favorecer la aparición de infecciones oportunistas (hongos, bacterias), algo que habrá que evaluar con un mayor número de pacientes. Había caída del dímero D y no se observaron episodios trombóticos. Otros parámetros son difíciles de evaluar dado el bajo número de datos. El balance fue de dos personas fallecidas y 11 recuperadas más o menos rápidamente (9 de ellos en un tiempo medio de una semana).

Item Type:Article
Uncontrolled Keywords:COVID-19; SARS-CoV-2; Pneumonia; Mechanical ventilation; Mesenchymal stromal cells; Cellular therapy; Case series
Subjects:Medical sciences > Medicine > Communicable diseases
Medical sciences > Biology > Cytology
ID Code:63535
Deposited On:13 Jan 2021 19:27
Last Modified:14 Jan 2021 08:34

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