Abstract
The aim of this clinical trial was to control the cytokine storm by administering mesenchymal stem cells (MSCs) to critically-ill COVID-19 patients, to evaluate the healing effect, and to systematically investigate how the treatment works. Patients with moderate and critical COVID-19 clinical manifestations were separated as Group 1 (moderate cases, n = 10, treated conventionally), Group 2 (critical cases, n = 10, treated conventionally), and Group 3 (critical cases, n = 10, treated conventionally plus MSCs transplantation therapy of three consecutive doses on treatment days 0, 3, and 6, (as 3 × 10 6 cells/kg, intravenously). The treatment mechanism of action was investigated with evaluation markers of the cytokine storm, via biochemical parameters, levels of proinflammatory and anti-inflammatory cytokines, analyses of tissue regeneration via the levels of growth factors, apoptosis markers, chemokines, matrix metalloproteinases, and granzyme-B, and by the assessment of the immunomodulatory effects via total oxidant/antioxidant status markers and the levels of lymphocyte subsets. In the assessment of the overall mortality rates of all the cases, six patients in Group-2 and three patients in Group-3 died, and there was no loss in Group-1. Proinflammatory cytokines IFNγ, IL-6, IL-17A, IL-2, IL-12, anti-inflammatory cytokines IL-10, IL-13, IL-1ra, and growth factors TGF-β, VEGF, KGF, and NGF levels were found to be significant in Group-3. When Group-2 and Group-3 were compared, serum ferritin, fibrinogen and CRP levels in Group-3 had significantly decreased. CD45 +, CD3 +, CD4 +, CD8 +, CD19 +, HLA-DR +, and CD16 + / CD56 + levels were evaluated. In the statistical comparison of the groups, significance was only determined in respect of neutrophils. The results demonstrated the positive systematic and cellular effects of MSCs application on critically ill COVID-19 patients in a versatile way. This effect plays an important role in curing and reducing mortality in critically ill patients.
Keywords: COVID-19; cytokines; growth factors; mesenchymal stem cell.
【저자키워드】 COVID-19, Cytokines, Growth factors, mesenchymal stem cell, 【초록키워드】 Treatment, Neutrophils, Apoptosis, Cytokine storm, clinical trial, therapy, Cytokines, IL-17A, IL-6, Lymphocyte subsets, Mesenchymal stem cells, MSCs, cytokine, chemokines, immunomodulatory effects, CD4, CD8, Growth factors, clinical manifestations, lymphocyte, proinflammatory, Critically ill, Patient, fibrinogen, matrix metalloproteinases, IL-10, proinflammatory cytokines, group, mechanism of action, Critical, moderate, HLA-DR, mesenchymal stem cell, critically ill patients, COVID-19 patients, IL-2, marker, IL-13, TGF-β, CD16, cellular, Analysis, dose, MSC, COVID-19 patient, critical cases, critically ill COVID-19 patients, CD19, stem cell, clinical manifestation, Biochemical parameters, Serum ferritin, tissue regeneration, overall mortality, growth, CRP levels, IFNγ, IL-1ra, reducing mortality, VEGF, growth factor, IL-12, CD45, CRP level, CD56, positive, intravenously, immunomodulatory effect, anti-inflammatory cytokines, anti-inflammatory cytokine, Effect, CD3, NGF, Cell, statistical, evaluate, died, significantly, investigated, evaluated, treated, demonstrated, groups, separated, KGF, the cytokine storm, 【제목키워드】 Prospective, mesenchymal stem cell, Effect, STEM, Controlled,