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 × 106 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-ß, 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.
Subject(s)
COVID-19/therapy , Mesenchymal Stem Cell Transplantation , Adult , C-Reactive Protein/analysis , COVID-19/pathology , COVID-19/virology , Critical Illness , Cytokines/blood , Female , Humans , Interferon-gamma/blood , Interleukin-10/blood , Interleukin-8/blood , Leukocyte Common Antigens/metabolism , Lymphocytes/cytology , Lymphocytes/metabolism , Male , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Middle Aged , Prospective Studies , SARS-CoV-2/isolation & purification , Severity of Illness Index , Treatment OutcomeABSTRACT
The aim of this study is to evaluate the therapeutic effect of mesenchymal stem cells (MSCs) in a severe case of brain and multiple organ involvement in a patient with COVID-19. Here, a 51-year-old male patient with multi-organ involvement due to COVID-19 infection and developing cardiac arrest is presented. MSCs were transplanted to the patient four times systematically and once intrathecally. As a result, the application of MSCs has been found to have a healing effect on organs in this patient with severe COVID-19 infection. In addition, transplantation of MSCs both systematically and intrathecally is considered to be effective in the treatment of the central nervous system (Tab. 2, Fig. 2, Ref. 24). Keywords: mesenchymal stem cell, COVID-19, organ involvement.