Mesenchymal Stem Cells for the Compassionate Treatment of Severe Acute Respiratory Distress Syndrome Due to COVID 19

Abstract

Mesenchymal stem cells (MSC) have received particular attention due to their ability to inhibit inflammation caused by cytokine storm induced by COVID-19. In this way some patients have been treated successfully. The aim of this study was to evaluate the safety and describe the clinical changes after IV administration of allogeneic human umbilical cord MSC (ahUCMSC), in patients with bilateral pneumonia caused by COVID-19, complicated with severe ARDS, as compassionate treatment. This was a pilot, open-label, prospective, longitudinal study. Five patients that did not improve in their clinical conditions after 48 hours of receiving the standard medical management used by the Medical Center and with persistent PaO2/FiO2 less than 100 mmHg were enrolled. ahUCMSC were infused IV, at dose of 1x10 6 per Kg of body weight over 15 minutes. Patients were monitored after the infusion to detect adverse event. Pa02/FiO2, vital signs, D-dimer, C reactive protein and total lymphocytes were monitored for 21 days after the infusion or until the patient was discharged from the hospital. Descriptive statistics were used with means or medians and standard deviation or interquartile range according to the type of variable. The Wilcoxon's rank-sum was used for stationary samples. Adverse events occurred in three patients and were easily and quickly controlled. Immediately after the infusion of ahUCMSC, constant rise of PaO2/FiO2 was observed in all patients during the first 7 days, with statistical significance. Three patients survived and were extubated on the ninth day post-infusion. Two patients died at 13 and 15 days after infusion. The infusion of ahUCMSC in patients with severe ARDS caused by COVID-19, was safe, and demonstrated its anti-inflammatory capacity in the lungs, by improving the respiratory function expressed by PaO2 / FiO2, which allowed the survival of 3 patients, with extubation at 9 days.

The safety and efficacy of mesenchymal stem cells in the treatment of COVID-19-associated pneumonia: a systematic review and meta-analysis

“…Abstract and full-text screening identified 22 studies with 371 patients to be included for the data extraction. All included studies were assessed as good [10,12,[22][23][24][25][26]32,35,36,38,39] or fair [13,[27][28][29][30][31]33,34,37,40] according to the NHLBI quality assessment tool (Table S2).…”

“…Culture-expanded allogeneic MSCs were used in all 22 included studies. Allogeneic umbilical cordderived MSCs were used in studies [22][23][24][25][26]29,30,32,34,[36][37][38][39], Wharton's jelly-derived MSCs in three studies [12,33,40], menstrual blood-or adipose tissue-or placenta-derived MSCs were separately used in one study [10,28,35]. Four studies did not report the tissue origin of the MSCs [13,27,31,37](Table 3).…”

“…Characterization was reported in most studies, with significant differences in details. Characterization of MSCs was reported in 11 studies, with most of the following markers: positive for CD9, CD29, CD44, CD73, CD90, CD105, HLA-ABC, and negative for CD11b, CD14, CD19, CD31, CD34, CD45, CD79α, CD133 and HLA-DR [10,12,13,[22][23][24][25][26]32,35,39]. Viability was reported to be >80% [10,12,[24][25][26][27]32,35,36,39].…”

“…The disease severity of the patient's condition was Critical (n = 63), Severe (n = 260), and Moderate (n = 10) in 19 studies [10,12,13,[22][23][24][25][27][28][29][30][31][32][33][34]36,[38][39][40]; and the patients in one study were divided into "Mild-to-moderate" (n = 6) and "Moderate-to-severe" (n = 18) according to the severity of ARDS [26]. The average age of study participants was 45.1 to 61.0 years for MSCs group and 39.0 to 65.0 years for control group in the comparative studies [13,[22][23][24][25][26][27].…”

“…The most common comorbidities including hypertension (HT, n = 105), diabetes mellitus (DM, n = 61), obesity(n = 19), chronic obstructive pulmonary disease (COPD, n = 11), and heart disease (HD, n = 9) had been reported in 18 studies [10,12,13,22,23,[25][26][27][28][29][30][32][33][34][35][38][39][40]. There were also differences in the follow-up time after MSCs treatment in these studies, ranging from a week to two months, which mainly due to the point when patients were recovery or died and discharge from the hospital (Table 1-2).…”