Specific Clinical and Immunological Changes Following Mesenchymal Stem Cell Transplantation in COVID-19–induced Acute Respiratory Distress Syndrome Patients: A Phase-I Clinical Trial

Najmeh  Kaffash Farkhad; Alireza  sedaghat; Hamidreza Reihani; Amir Adhami Moghadam; Ahmad  Bagheri Moghadam; Nayereh Khadem Ghaebi; Mohamad Ali Khodadoust; Amin Reza Nikpoor; Jalil  Tavakol-Afshari

doi:10.18502/ijaai.v21i6.11530

Najmeh Kaffash Farkhad Department of Immunology, Immunology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Alireza sedaghat Lung Disease Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Hamidreza Reihani Department of Emergency Medicine, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Amir Adhami Moghadam Department of Internal Medicine and Critical Care, Islamic Azad University, Mashhad, Iran
Ahmad Bagheri Moghadam Department of Anesthesiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Nayereh Khadem Ghaebi Neonatal Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Mohamad Ali Khodadoust Department of Immunology, Immunology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
Amin Reza Nikpoor Molecular Medicine Research Center, Hormozgan Health Institute, Hormozgan University of Medical Sciences, Bandar Abbas, Iran
Jalil Tavakol-Afshari Department of Immunology, Immunology Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

DOI: https://doi.org/10.18502/ijaai.v21i6.11530

Keywords: Acute respiratory distress syndrome; Immunological biomarkers; Inflammation; Lymphopenia; Mesenchymal stem cells

Abstract

Acute respiratory distress syndrome (ARDS) is a systemic inflammation resulting from immune system overactivity. ARDS is also a fatal complication of COVID-19. Mesenchymal stem cells (MSCs) have immune modulatory properties. This study evaluated the safety and efficacy of three times transplantation of umbilical cord-derived MSCs (UC-MSCs) in terms of specific immunological and clinical changes in mild-to-moderate COVID-19-induced ARDS patients.

In this single-center, open-label, phase 1 clinical trial, 20 patients diagnosed with COVID-19 and mild-to-moderate ARDS were included and were divided into two groups: a control group receiving standard care and an intervention group receiving UC-MSC in addition to standard care. Three consecutive intravenous transplants of UC-MSC (1× cells/kg body weight per each transplant) were performed in the intervention group on days 1, 3, and 5. The biological assay was investigated four times (days 0, 5, 10, and 17).

UC-MSCs improved the patients' clinical and paraclinical parameters, including leukocytosis, lymphopenia, thrombocytopenia, and liver enzyme abnormalities compared to the control group. They also decreased pro-inflammatory lymphocytes (TH1 and TH17) and increased anti-inflammatory T lymphocytes. Cell therapy also reduced the mean fluorescence intensity (MFI) in overactivated CD8⁺ T cells.

These findings show that three UC-MSC injections could regulate a hyperactivated immune system in COVID-19-induced ARDS patients by decreasing the inflammatory T lymphocyte subset and can improve the patient's hematological condition and liver function. However, more studies are needed in this area.