| Autor: |
Dwivedi A; Trinity Kidney Centre, School of Medicine, and., Ui Mhaonaigh A; Trinity Kidney Centre, School of Medicine, and., Carroll M; Trinity Kidney Centre, School of Medicine, and., Khosravi B; Trinity Kidney Centre, School of Medicine, and., Batten I; Department of Medical Gerontology, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland., Ballantine RS; Trinity Kidney Centre, School of Medicine, and., Hendricken Phelan S; Wellcome Trust, Clinical Research Facility., O'Doherty L; Wellcome Trust, Clinical Research Facility.; Department of Infectious Diseases; and., George AM; Department of Immunology, St James's Hospital, Dublin, Ireland., Sui J; Department of Medical Gerontology, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland.; Department of Immunology, St James's Hospital, Dublin, Ireland., Hawerkamp HC; School of Medicine, Trinity Biomedical Sciences Institute., Fallon PG; School of Medicine, Trinity Biomedical Sciences Institute.; Department of Immunology, Trinity Translational Medicine Institute; and., Noppe E; Department of Critical Care, Tallaght University Hospital, Trinity College Dublin, Dublin, Ireland., Mason S; Department of Critical Care, Tallaght University Hospital, Trinity College Dublin, Dublin, Ireland., Conlon N; Department of Infectious Diseases; and.; Department of Immunology, St James's Hospital, Dublin, Ireland., Ni Cheallaigh C; Department of Infectious Diseases; and., Finlay CM; Trinity Kidney Centre, School of Medicine, and., Little MA; Trinity Kidney Centre, School of Medicine, and., Bioresource OBOTSJATTARS; The STTAR Bioresource is detailed in Supplemental Acknowledgments. |
| Abstrakt: |
Neutrophilia occurs in patients infected with SARS-CoV-2 (COVID-19) and is predictive of poor outcomes. Here, we link heterogenous neutrophil populations to disease severity in COVID-19. We identified neutrophils with features of cellular aging and immunosuppressive capacity in mild COVID-19 and features of neutrophil immaturity and activation in severe disease. The low-density neutrophil (LDN) number in circulating blood correlated with COVID-19 severity. Many of the divergent neutrophil phenotypes in COVID-19 were overrepresented in the LDN fraction and were less detectable in normal-density neutrophils. Functionally, neutrophils from patients with severe COVID-19 displayed defects in neutrophil extracellular trap formation and reactive oxygen species production. Soluble factors secreted by neutrophils from these patients inhibited T cell proliferation. Neutrophils from patients with severe COVID-19 had increased expression of arginase-1 protein, a feature that was retained in convalescent patients. Despite this increase in intracellular expression, there was a reduction in arginase-1 release by neutrophils into serum and culture supernatants. Furthermore, neutrophil-mediated T cell suppression was independent of arginase-1. Our results indicate the presence of dysfunctional, activated, and immature neutrophils in severe COVID-19. |
