Umbilical Cord Mesenchymal Stromal Cells as Critical COVID-19 Adjuvant Therapy: A Randomized Controlled Trial

Abstract

One of the main causes of acute respiratory distress syndrome in coronavirus disease 2019 (COVID-19) is cytokine storm, although the exact cause is still unknown. Umbilical cord mesenchymal stromal cells (UC-MSCs) influence proinflammatory T-helper 2 (Th 2 ) cells to shift to an anti-inflammatory agent. To investigate efficacy of UC-MSC administration as adjuvant therapy in critically ill patients with COVID-19, we conducted a double-blind, multicentered, randomized controlled trial at four COVID-19 referral hospitals in Jakarta, Indonesia. This study included 40 randomly allocated critically ill patients with COVID-19; 20 patients received an intravenous infusion of 1 Â 10 6 /kg body weight UC-MSCs in 100 ml saline (0.9%) solution (SS) and 20 patients received 100 ml 0.9% SS as the control group. All patients received standard therapy. The primary outcome was measured by survival rate and/or length of ventilator usage. The secondary outcome was measured by clinical and laboratory improvement, with serious adverse events. Our study showed the survival rate in the UC-MSCs group was 2.5 times higher than that in the control group (P = .047), which is 10 patients and 4 patients in the UC-MSCs and control groups, respectively. In patients with comorbidities, UC-MSC administration increased the survival rate by 4.5 times compared with controls. The length of stay in the intensive care unit and ventilator usage were not statistically significant, and no adverse events were reported. The application of infusion UC-MSCs significantly decreased interleukin 6 in the recovered patients (P = .023). Therefore, application of intravenous UC-MSCs as adjuvant treatment for critically ill patients with COVID-19 increases the survival rate by modulating the immune system toward an antiinflammatory state.

Antibody and cellular therapies for treatment of covid-19: a living systematic review and network meta-analysis

“…After screening 52350 titles and abstracts and 1029 full texts, 47 unique randomised controlled trials that evaluated antiviral antibody or cellular treatments were identified as of 21 July 2021 (fig 1). 43444546474849505152535455565758596061626364656667686970717273747576777879808182838485868788 A table of excluded full texts is provided in the supplementary data on bmj.com. Searches of living evidence retrieval services identified 11 publications of eligible randomised trials, which were reconciled with our formal search strategy when necessary 222324254549566466676875838688.…”

“…One randomised trial was identified after the data analysis: Dilogo 202153 (registration No NCT04457609), a trial of umbilical cord mesenchymal stromal cells versus placebo in 40 participants. It will be included in the next update.…”

Effectivity of mesenchymal stem cells for bleomycin-induced pulmonary fibrosis: a systematic review and implication for clinical application

“…Phase I and II clinical studies have shown that MSCs transplantation is a safe and potentially effective method for the treatment of moderate to severe ARDS [63,64]. Besides, recent exploratory clinical studies showed that MSCs treatment was associated with improvements in mortality, dyspnea and chest imaging findings for severe and critically ill COVID-19 patients [65][66][67][68][69]. And phase I and II clinical trials have also shown that intravenous MSCs infusion in patients with moderate and severe COVID-19 is safe and well tolerated [70,71].…”

Umbilical cord tissue-derived mesenchymal stem cells should be considered as adjuvant therapy for COVID-19 treatment: An opinion from pooled clinical evidence

“…In some case reports, the UC- MSC transplantation also improved lung inflammation based on lung CT images 32,34,35, 38 . The laboratory tests showed that almost all patients treated with UC-MSC transplantation had decreased CRP, IL-6, and TNF-α 5,26-28, 31 , and this reduction could be detected early in days 2 -3 post-transplantation [31,40] or later at 7 -14 days post-transplantation 26,28 . However, Wei et al (2021) showed that although there were significant improvements in symptoms, the biomarkers of CRP, IL-6, and TNF-α were not significantly reduced after 1 -3, 5 -8, and 12 -16 days following UC-MSC infusion 24 in a study of 12 patients.…”