Clémence Marais1,2, Caroline Claude1,2, Nada Semaan1,2, Ramy Charbel1, Simon Barreault1,2, Brendan Travert1,3, Jean-Eudes Piloquet1,3, Zoé Demailly4, Luc Morin1,2, Zied Merchaoui1, Jean-Louis Teboul4, Philippe Durand1, Jordi Miatello1,2, Pierre Tissières5,6,7. 1. Pediatric « Adult COVID-19-Converted » Intensive Care and Neonatal Medicine, AP-HP Paris Saclay University, Bicêtre Hospital, 78, Rue du Général Leclerc, 94275, Le Kremlin-Bicêtre, France. 2. Institute of Integrative Biology of the Cell, CNRS, CEA, Univ. Paris Saclay, Gif-sur-Yvette, France. 3. Pediatric Intensive Care, Nantes University Hospital, Nantes, France. 4. Medical Intensive Care, AP-HP Paris Saclay University, Bicêtre Hospital, Le Kremlin-Bicêtre, France. 5. Pediatric « Adult COVID-19-Converted » Intensive Care and Neonatal Medicine, AP-HP Paris Saclay University, Bicêtre Hospital, 78, Rue du Général Leclerc, 94275, Le Kremlin-Bicêtre, France. pierre.tissieres@aphp.fr. 6. Institute of Integrative Biology of the Cell, CNRS, CEA, Univ. Paris Saclay, Gif-sur-Yvette, France. pierre.tissieres@aphp.fr. 7. FHU SEPSIS, AP-HP/Université Paris Saclay/Inserm, Le Kremlin-Bicêtre, France. pierre.tissieres@aphp.fr.
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.
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-19critically illpatients. 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 illCOVID-19patients may be associated with development of secondary infection, 28- and 60-day mortality.
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