Myeloid phenotypes in severe COVID-19 predict secondary infection and mortality: a pilot study
Clémence Marais, Caroline Claude, Nada Semaan, Ramy Charbel, Simon Barreault, Brendan Travert, Jean‐Eudes Piloquet, Zoé Demailly, Luc Morin, Zied Merchaoui, Jean–Louis Teboul, Philippe Durand, Jordi Miatello, Pierre Tissières, Simon Barreault, Simon Barreault, Mélissa Beggaz, Ramy Charbel, Caroline Claude, Philippe Durand, Philippe Durand, Gaspard Gerschenfeld, Jessica Giraldi, Matteo Guerra, Manon Hily, Martin Journaux, Christopher Lai, Pauline Leroux, Zied Merchaoui, Zied Merchaoui, Jordi Miatello, Clarisse Niçaise, Melissa Ren, Melissa Ren, Marie Simbozel, Nada Semaan, Jean–Louis Teboul, Pierre Tissières
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.