Abstract

Objective: Deficiencies in immune-regulatory mechanisms such as immune activation and T-regulatory cells are classically referred to as cytokine storms. Mesenchymal stem cells (MSCs) act as living anti-inflammatory cells that can rebalance cytokine/immune responses to restore balance in patients with coronavirus disease-2019 (COVID-19) acute respiratory distress syndrome by reducing the activation of T and B cells, and dendritic and natural killer cells. The aim of this study is to provide immune modulation with stem cell transplantation by reducing the damage caused and COVID-19 infection to tissues and organs. Material and Methods: In this prospective randomized single-center clinical trial, patients were divided into 3 groups: intubated without comorbidity (n=7); intubated with comorbidity (n=7); not intubated (n=7). Dosage of MSCs transplantation for each group was 1 million cell/kg intravenous at days 0, 2, and 4. age, gender, APACHE II scores, procalcitonin, C-reactive protein (CRP) and leukocyte values, and cluster of difference 4 (CD4), CD8, interleukin 2 (IL-2), and IL-6 levels, morbidities, number of days in intensive care unit, mortality were recorded. Clinical results, changes in inflammatory and immune function levels, and side effects were evaluated. Each patient's improvement in oxygenation and symptoms were recorded in the days after MSC transplantation. After treatment, lymphocyte, CRP, tumor necrosis factor-α level, and IL-6 levels were recorded. Results: There was no statistically significant difference between the three groups in terms of stem cell therapy patients' age and exit/discharge days and mortality. Patients who were in the group of 'intubated, no comorbidity' had significantly higher CD19 and CD19+HLA-DR+ values compared with patients in the groups of 'intubated with comorbidity' and 'not intubated.' CRP, FiO2, IL-6 and SpO2 values were significantly different across periods. Conclusion: Our study may found a useful effect of MSCs on severe COVID-19 pneumonia and showed reversal of hypoxia and downregulation of cytokine storm in patients with severe COVID-19 following 3 intravenous doses with no adverse effects assignable to the treatment.

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