Research Article Volume 4 • Issue 4 152 The Importance of Timing in the Application of Mesenchymal Stem Cells in Critically Ill Patients with COVID-19 infection (Retrospective study) Rabia Yilmaz 1* , Zafer Çukurova 1 , Gülsüm Oya Hergünsel 1 , Sinan Aşar 1 , Erdal Karaöz 2,4 , Nilgün Işiksaçan 5 , Gökhan Tolga Adaş 6,7 Afliation: 1 Department of Anesthesia and Intensive Care, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Seciences, Istanbul/ Turkey 2 Liv Hospital, Center for Regenerative Medicine and Stem Cell Manufacturing, Istanbul/Turkey 3 Istinye University, Faculty of Medicine, Department of Histology&Embryology, Istanbul/Turkey 4 Istinye University, Center for Stem Cell and Tissue Engineering Research&Practice, Istanbul/Turkey 5 Department of Biochemistry and Immunology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Seciences, Istanbul/ Turkey 6 Department of Surgery, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Seciences, Istanbul/Turkey 7 Head of Stem Cell and Gene Therapies Application and Research Center, University of Health Seciences, Istanbul/Turkey Corresponding author: Rabia Yilmaz, Department of Anesthesiology, Division of Intensive Care, Bakirkoy Dr. Sadi Konuk Trainig and Research Hospital, Istanbul, Turkey Citation: Rabia Yilmaz, Zafer Çukurova, Gülsüm Oya Hergünsel, Sinan Aşar, Erdal Karaöz, Nilgün Işiksaçan, Gökhan Tolga Adaş, José RA Azevedo. The Importance of Timing in the Application of Mesenchymal Stem Cells in Critically Ill Patients with COVID-19 infection (Retrospective study). Anesthesia and Critical care 4 (2022): 152-159 Received: July 30, 2022 Accepted: August 09 2022 Published: October 25, 2022 Abstract Background: The aim of this study is to control the disease by administering MSC treatment to COVID-19 patients who are taken into intensive care unit, and to assess at what time period the MSC transplant has a more positive curative efect on COVID-19 infection. Methods: Group 1 (n=32): the frst administration of MSCs was started within 1-4 days, Group 2 (n=36): the frst administration of MSCs was started within 4-8 days, Group 3 (n=36): the frst administration of MSCs was started within 8-12 days. The main parameters investigated: COVID-19 infammation markers, length of hospital stay, and mortality rates. Results: In our study, 54 (52%) of 104 patients died and 50 patients (48%) were discharged with recovery. When we evaluated the mortality rates between the groups, 10 patients (31%) in group-, 20 patients (56%) in group-2 and 24 patients (67%) in group-3 died, respectively. The groups were compared statistically, the mortality rate was signifcant in favor of group-1 (p<0,05). When the groups were compared in terms of COVID-19 infammation markers, CRP and D-dimer levels of group-1 were found to be lower than the other groups (p<0.05). Conclusions: Administration of MSCs in the early time period reduces mortality in critically ill patients with COVID-19. Keywords: MSCs timing; COVID-19; Intensive Care Introduction COVID-19 virus enters the human cell binding, through its S spike protein, to Angiotensin-Converting Enzyme-2 (ACE2) receptor present on type-2 alveoli cells, endothelial cells, heart, kidney, liver and other organs [1]. A rapid and well-coordinated innate immune response is the frst line of defense against viral infections, but dysregulated and excessive immune responses may cause immunopathology [2,3]. Mesenchymal stem cells (MSCs) can act as immunosuppressants or immunostimulators. In a cell anergy context, they could exhibit a pro-infammatory phenotype, MSC-1, making it possible to reduce apoptosis and promote T-cell survival. On the other hand, in case of infammation, they could adoptan immunosuppressive and anti-infammatory phenotype, called MSC-2 [4]. Previous studies have shown that MSCs plays a role as an immune modulator in cytokine storm developing due to infammation. Exogenous MSCs have been used as immunomodulators in cytokine storm in conditions such as acute pancreatitis, acute and chronic lung diseases [5,6]. MSCs application proved therapeutic efciency during