Author:
Zarrabi Morteza,Shahrbaf Mohammad Amin,Nouri Masoumeh,Shekari Faezeh,Hosseini Seyedeh-Esmat,Hashemian Seyed-Mohammad Reza,Aliannejad Rasoul,Jamaati Hamidreza,Khavandgar Naghmeh,Alemi Hediyeh,Madani Hoda,Nazari Abdoreza,Amini Azadeh,Hassani Seyedeh Nafiseh,Abbasi Fatemeh,Jarooghi Neda,Fallah Nasrin,Taghiyar Leila,Ganjibakhsh Meysam,Hajizadeh-Saffar Ensiyeh,Vosough Massoud,Baharvand Hossein
Abstract
Abstract
Background and aims
The main causes of death in patients with severe Coronavirus disease-2019 (COVID-19) are acute respiratory distress syndrome (ARDS) and multiorgan failure caused by a severe inflammatory cascade. Novel treatment strategies, such as stem-cell-based therapy and their derivatives can be used to relieve inflammation in these cases. In this study, we aimed to evaluate the safety and efficacy of therapy using mesenchymal stromal cells (MSCs) and their derived extracellular vesicles in COVID-19 patients.
Materials and methods
COVID-19 patients with ARDS were included in this study and allocated into two study and control groups using block randomization. While all patients received recommended treatment based on guidelines from the national advisory committee for COVID-19 pandemic, the two intervention groups received two consecutive injections of MSCs (100 × 106 cells) or one dose of MSCs (100 × 106 cells) followed by one dose of MSC-derived extracellular vesicles (EVs). Patients were assessed for safety and efficacy by evaluating clinical symptoms, laboratory parameters, and inflammatory markers at baseline and 48 h after the second intervention.
Results
A total number of 43 patients (the MSC alone group = 11, MSC plus EV group = 8, and control group = 24) were included in the final analysis. Mortality was reported in three patients in the MSC alone group (RR: 0.49; 95% CI 0.14–1.11; P = 0.08); zero patient in the MSC plus EV group (RR: 0.08; 95% CI 0.005–1.26; P = 0.07) and eight patients in the control group. MSC infusion was associated with a decrease in inflammatory cytokines such as IL-6 (P = 0.015), TNF-α (P = 0.034), IFN-γ (P = 0.024), and CRP (P = 0.041).
Conclusion
MSCs and their extracellular vesicles can significantly reduce the serum levels of inflammatory markers in COVID-19 patients, with no serious adverse events.
Trial registration IRCT, IRCT registration number: IRCT20200217046526N2. Registered 13th April 2020, http://www.irct.ir/trial/47073.
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Biochemistry, Genetics and Molecular Biology (miscellaneous),Molecular Medicine,Medicine (miscellaneous)
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