Emergence of dysfunctional neutrophils with a defect in arginase-1 release in severe COVID-19

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 fea...

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Published in:	JCI insight Vol. 9; no. 17
Main Authors:	Dwivedi, Amrita, Ui Mhaonaigh, Aisling, Carroll, Makala, Khosravi, Bahareh, Batten, Isabella, Ballantine, Robert Seán, Hendricken Phelan, Stuart, O'Doherty, Laura, George, Angel Mary, Sui, Jacklyn, Hawerkamp, Heike C, Fallon, Padraic G, Noppe, Elnè, Mason, Sabina, Conlon, Niall, Ni Cheallaigh, Clíona, Finlay, Conor M, Little, Mark A, Bioresource, On Behalf Of The St James's And Tallaght Trinity Allied Researchers Sttar
Format:	Journal Article
Language:	English
Published:	United States American Society for Clinical Investigation 10-09-2024
Subjects:	Adult Aged Arginase - metabolism COVID-19 - blood COVID-19 - immunology Extracellular Traps - immunology Extracellular Traps - metabolism Female Humans Male Middle Aged Neutrophil Activation Neutrophils - immunology Neutrophils - metabolism Reactive Oxygen Species - metabolism SARS-CoV-2 - immunology Severity of Illness Index T-Lymphocytes - immunology T-Lymphocytes - metabolism COVID-19 Immunology Neutrophils
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Authorship note: AD and AUM are co–first authors. CMF and MAL contributed equally to this work.
ISSN:	2379-3708 2379-3708
DOI:	10.1172/jci.insight.171659