Myeloid phenotypes in severe COVID-19 predict secondary infection and mortality: a pilot study

Abstract

Background De-regulated host response to severe coronavirus disease 2019 (COVID-19), directly referring to the concept of sepsis-associated immunological dysregulation, seems to be a strong signature of severe COVID-19. Myeloid cells phenotyping is well recognized to diagnose critical illness-induced immunodepression in sepsis and has not been well characterized in COVID-19. The aim of this study is to review phenotypic characteristics of myeloid cells and evaluate their relations with the occurrence of secondary infection and mortality in patients with COVID-19 admitted in an intensive care unit. Methods Retrospective analysis of the circulating myeloid cells phenotypes of adult COVID-19 critically ill patients. Phenotyping circulating immune cells was performed by flow cytometry daily for routine analysis and twice weekly for lymphocytes and monocytes subpopulations analysis, as well as monocyte human leukocyte antigen (mHLA)-DR expression. Results Out of the 29 critically ill adult patients with severe COVID-19 analyzed, 12 (41.4%) developed secondary infection and six patients died during their stay. Monocyte HLA-DR kinetics was significantly different between patients developing secondary infection and those without, respectively, at day 5–7 and 8–10 following admission. The monocytes myeloid-derived suppressor cells to total monocytes ratio was associated with 28- and 60-day mortality. Those myeloid characteristics suggest three phenotypes: hyperactivated monocyte/macrophage is significantly associated with mortality, whereas persistent immunodepression is associated with secondary infection occurrence compared to transient immunodepression. Conclusions Myeloid phenotypes of critically ill COVID-19 patients may be associated with development of secondary infection, 28- and 60-day mortality.

Low Levels of Granulocytic Myeloid-Derived Suppressor Cells May Be a Good Marker of Survival in the Follow-Up of Patients With Severe COVID-19

“…In line with this, it has been found that cells with MDSC features are implicated in COVID-19, and several reports have described the accumulation of potent immunosuppressive M-MDSCs and G-MDSCs in the disease (4,27,28). In fact, a high M-MDSC/monocyte ratio has been associated with secondary infections and death due to the disease (29); the granulocytic subset has also been associated with mortality in severe COVID-19 (7). We aimed to analyze MDSCs, namely, the monocytic (M-MDSCs) and granulocytic (G-MDSCs) subsets, and the lymphocyte subpopulations in patients with severe COVID-19 from admission into the ICU and during the follow-up until discharge or death.…”

Integrated Single Cell and Bulk RNA-Seq Analysis Revealed Immunomodulatory Effects of Ulinastatin in Sepsis: A Multicenter Cohort Study

“…While neutrophil fraction was significantly reduced with UTI treatment , the MDSC fraction was significantly expanded in the UTI group (-1.22, -0.66); p = 0.002]. MDSCs constitute a heterogeneous population of immature myeloid cells that potently suppress immune responses, and is enriched in sepsis ( 42 – 44 ). However, the regulatory mechanism of MDSC expansion in sepsis is unknown.…”

Myeloid-derived suppressor cells in COVID-19: A review

“…Specifically in the respiratory tract, viral destruction of alveolar cells and bronchial epithelial cells, along with mass production of cytokines, leads to pneumonia and, in severe cases, acute respiratory distress syndrome (ARDS) [ 45 , 46 ]. Although the full picture of COVID-19 pathogenesis remains to be investigated, it is now clear that the cytokine and chemokine profile observed in COVID-19 patients promotes profound changes in myeloid cells that appear to be able to determine the outcome of infection [ 5 , 47 ].…”