Investigation of phenotypic and functional differences of G-MDSC-like subgroups in COVID-19 positive patients

Myeloid cells represent a diverse range of innate leukocytes. They are critical players for orchestrate initiating and coordinating immune responses against viruses. These cells arise from bone marrow with inflammatory signals and circulate into the bloodstream in mature/immature form. Moreover, they play unique immuno-regulatory roles in post-infection, and are critical for restoring homeostasis. In cases where the balance of the immune system is destroyed, over or insufficient inflammation occurs in response to viruses. Effective and coordinated immune responses control viral replication and prevent the cytokine storms. As a results, this situation would limits immuno-pathology and supports fevribla clinical outcome. In this thesis, we investigated myeloid-derived suppressor cells and other myeloid cell subgroups affect on COVID-19 prognosis. Experiments were performed with peripheral blood samples from both children and adults who were prediagnosed with COVID-19 and disease was confirmed by PCR test. G-MDSC levels of these patients were evaluated phenotypically and functionally, their interactions with other myeloid cells were investigated and overall these resutls were associated with the clinical outcome. High proportion of G-MDSC and E-MDSC was observed in children diagnosed with COVID-19 (0-13 years old), and E-MDSC increased while G-MDSC decreased in acute phase of disease. There was no significant difference was observed in M-MDSC subgroup. These results indicate that MDSCs have two-sided effect on immune responses in children. Despite the presence of a suppressor cell group, especially in acute phase of anti-viral immune responses, the presence of high levels of other pro-inflammatory myeloid cell subgroups is thought to control effective immune response. Consistent with the literature, it was determined that the increasement of M-MDSC in adults diagnosted with COVID-19, is associated with a poor prognosis and these cells were increased in patients with a severe disease. It has been determined that the M-MDSC/G-MDSC ratio ≥1 and low E-MDSC ratio in adults diagnosed with COVID-19 could be a marker for poor prognosis. Keywords: Immune responses of COVID-19, myeloid derived suppressor cells, immune modulation, neutrophils, T cell responses