A specific low-density neutrophil population correlates with hypercoagulation and disease severity in hospitalized COVID-19 patients
SARS coronavirus 2 (SARS-CoV-2) is a novel viral pathogen that causes a clinical disease called coronavirus disease 2019 (COVID-19). Although most COVID-19 cases are asymptomatic or involve mild upper respiratory tract symptoms, a significant number of patients develop severe or critical disease. Pa...
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doaj-cd228fc8771e4fcab54acb1172e0ffbe2021-08-02T22:31:08ZengAmerican Society for Clinical investigationJCI Insight2379-37082021-05-0169A specific low-density neutrophil population correlates with hypercoagulation and disease severity in hospitalized COVID-19 patientsSamantha M. MorrisseyAnne E. GellerXiaoling HuDavid TieriChuanlin DingChristopher K. KlaesElizabeth A. CookeMatthew R. WoesteZachary C. MartinOscar ChenSarah E. BushHuang-ge ZhangRodrigo CavallazziSean P. CliffordJames ChenSmita GhareShirish S. BarveLu CaiMaiying KongEric C. RouchkaKenneth R. McLeishSilvia M. UriarteCorey T. WatsonJiapeng HuangJun YanSARS coronavirus 2 (SARS-CoV-2) is a novel viral pathogen that causes a clinical disease called coronavirus disease 2019 (COVID-19). Although most COVID-19 cases are asymptomatic or involve mild upper respiratory tract symptoms, a significant number of patients develop severe or critical disease. Patients with severe COVID-19 commonly present with viral pneumonia that may progress to life-threatening acute respiratory distress syndrome (ARDS). Patients with COVID-19 are also predisposed to venous and arterial thromboses that are associated with a poorer prognosis. The present study identified the emergence of a low-density inflammatory neutrophil (LDN) population expressing intermediate levels of CD16 (CD16Int) in patients with COVID-19. These cells demonstrated proinflammatory gene signatures, activated platelets, spontaneously formed neutrophil extracellular traps, and enhanced phagocytic capacity and cytokine production. Strikingly, CD16Int neutrophils were also the major immune cells within the bronchoalveolar lavage fluid, exhibiting increased CXCR3 but loss of CD44 and CD38 expression. The percentage of circulating CD16Int LDNs was associated with D-dimer, ferritin, and systemic IL-6 and TNF-α levels and changed over time with altered disease status. Our data suggest that the CD16Int LDN subset contributes to COVID-19–associated coagulopathy, systemic inflammation, and ARDS. The frequency of that LDN subset in the circulation could serve as an adjunct clinical marker to monitor disease status and progression.https://doi.org/10.1172/jci.insight.148435COVID-19Immunology |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Samantha M. Morrissey Anne E. Geller Xiaoling Hu David Tieri Chuanlin Ding Christopher K. Klaes Elizabeth A. Cooke Matthew R. Woeste Zachary C. Martin Oscar Chen Sarah E. Bush Huang-ge Zhang Rodrigo Cavallazzi Sean P. Clifford James Chen Smita Ghare Shirish S. Barve Lu Cai Maiying Kong Eric C. Rouchka Kenneth R. McLeish Silvia M. Uriarte Corey T. Watson Jiapeng Huang Jun Yan |
spellingShingle |
Samantha M. Morrissey Anne E. Geller Xiaoling Hu David Tieri Chuanlin Ding Christopher K. Klaes Elizabeth A. Cooke Matthew R. Woeste Zachary C. Martin Oscar Chen Sarah E. Bush Huang-ge Zhang Rodrigo Cavallazzi Sean P. Clifford James Chen Smita Ghare Shirish S. Barve Lu Cai Maiying Kong Eric C. Rouchka Kenneth R. McLeish Silvia M. Uriarte Corey T. Watson Jiapeng Huang Jun Yan A specific low-density neutrophil population correlates with hypercoagulation and disease severity in hospitalized COVID-19 patients JCI Insight COVID-19 Immunology |
author_facet |
Samantha M. Morrissey Anne E. Geller Xiaoling Hu David Tieri Chuanlin Ding Christopher K. Klaes Elizabeth A. Cooke Matthew R. Woeste Zachary C. Martin Oscar Chen Sarah E. Bush Huang-ge Zhang Rodrigo Cavallazzi Sean P. Clifford James Chen Smita Ghare Shirish S. Barve Lu Cai Maiying Kong Eric C. Rouchka Kenneth R. McLeish Silvia M. Uriarte Corey T. Watson Jiapeng Huang Jun Yan |
author_sort |
Samantha M. Morrissey |
title |
A specific low-density neutrophil population correlates with hypercoagulation and disease severity in hospitalized COVID-19 patients |
title_short |
A specific low-density neutrophil population correlates with hypercoagulation and disease severity in hospitalized COVID-19 patients |
title_full |
A specific low-density neutrophil population correlates with hypercoagulation and disease severity in hospitalized COVID-19 patients |
title_fullStr |
A specific low-density neutrophil population correlates with hypercoagulation and disease severity in hospitalized COVID-19 patients |
title_full_unstemmed |
A specific low-density neutrophil population correlates with hypercoagulation and disease severity in hospitalized COVID-19 patients |
title_sort |
specific low-density neutrophil population correlates with hypercoagulation and disease severity in hospitalized covid-19 patients |
publisher |
American Society for Clinical investigation |
series |
JCI Insight |
issn |
2379-3708 |
publishDate |
2021-05-01 |
description |
SARS coronavirus 2 (SARS-CoV-2) is a novel viral pathogen that causes a clinical disease called coronavirus disease 2019 (COVID-19). Although most COVID-19 cases are asymptomatic or involve mild upper respiratory tract symptoms, a significant number of patients develop severe or critical disease. Patients with severe COVID-19 commonly present with viral pneumonia that may progress to life-threatening acute respiratory distress syndrome (ARDS). Patients with COVID-19 are also predisposed to venous and arterial thromboses that are associated with a poorer prognosis. The present study identified the emergence of a low-density inflammatory neutrophil (LDN) population expressing intermediate levels of CD16 (CD16Int) in patients with COVID-19. These cells demonstrated proinflammatory gene signatures, activated platelets, spontaneously formed neutrophil extracellular traps, and enhanced phagocytic capacity and cytokine production. Strikingly, CD16Int neutrophils were also the major immune cells within the bronchoalveolar lavage fluid, exhibiting increased CXCR3 but loss of CD44 and CD38 expression. The percentage of circulating CD16Int LDNs was associated with D-dimer, ferritin, and systemic IL-6 and TNF-α levels and changed over time with altered disease status. Our data suggest that the CD16Int LDN subset contributes to COVID-19–associated coagulopathy, systemic inflammation, and ARDS. The frequency of that LDN subset in the circulation could serve as an adjunct clinical marker to monitor disease status and progression. |
topic |
COVID-19 Immunology |
url |
https://doi.org/10.1172/jci.insight.148435 |
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