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Adipose-derived mesenchymal stromal cells for the treatment of patients with
severe SARS-CoV-2 pneumonia requiring mechanical ventilation A proof of concept
study
#MMPMID32838232
Sánchez-Guijo F
; García-Arranz M
; López-Parra M
; Monedero P
; Mata-Martínez C
; Santos A
; Sagredo V
; Álvarez-Avello JM
; Guerrero JE
; Pérez-Calvo C
; Sánchez-Hernández MV
; Del-Pozo JL
; Andreu EJ
; Fernández-Santos ME
; Soria-Juan B
; Hernández-Blasco LM
; Andreu E
; Sempere JM
; Zapata AG
; Moraleda JM
; Soria B
; Fernández-Avilés F
; García-Olmo D
; Prósper F
EClinicalMedicine
2020[Aug]; 25
(?): 100454
PMID32838232
show ga
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 × 10(6) (IQR
0.50 × 10(6)) 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.
FUNDING: None.