Increased Peripheral Blood Neutrophil Activation Phenotypes and Neutrophil Extracellular Trap Formation in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients: A Case Series and Review of the Literature.

COVID-19 Critical Illness Extracellular Traps Humans Neutrophil Activation Neutrophils Phenotype SARS-CoV-2
COVID-19 NETosis NETs neutrophil

Journal

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
ISSN: 1537-6591
Titre abrégé: Clin Infect Dis
Pays: United States
ID NLM: 9203213

Informations de publication

Date de publication:
11 02 2022
Historique:
received: 05 03 2021
pubmed: 15 5 2021
medline: 17 2 2022
entrez: 14 5 2021
Statut: ppublish

Résumé

Increased inflammation has been well defined in coronavirus disease 2019 (COVID-19), while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils are known to contribute to immunopathology in infections, inflammatory diseases, and acute respiratory distress syndrome, a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets. Blood was obtained serially from critically ill COVID-19 patients for 11 days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis, and cytokine levels were assessed. Lung tissue was obtained immediately postmortem for immunostaining. PubMed searches for neutrophils, lung, and COVID-19 yielded 10 peer-reviewed research articles in English. Elevations in neutrophil-associated cytokines interleukin 8 (IL-8) and interleukin 6, and general inflammatory cytokines IFN-inducible protien-19, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin 1β, interleukin 10, and tumor necrosis factor, were identified both at first measurement and across hospitalization (P < .0001). COVID-19 neutrophils had exaggerated oxidative burst (P < .0001), NETosis (P < .0001), and phagocytosis (P < .0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected lungs available for examination (2 of 5). While elevations in IL-8 and absolute neutrophil count correlated with disease severity, plasma IL-8 levels alone correlated with death. Literature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. Importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data show that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst.

Sections du résumé

BACKGROUND
Increased inflammation has been well defined in coronavirus disease 2019 (COVID-19), while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils are known to contribute to immunopathology in infections, inflammatory diseases, and acute respiratory distress syndrome, a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets.
METHODS
Blood was obtained serially from critically ill COVID-19 patients for 11 days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis, and cytokine levels were assessed. Lung tissue was obtained immediately postmortem for immunostaining. PubMed searches for neutrophils, lung, and COVID-19 yielded 10 peer-reviewed research articles in English.
RESULTS
Elevations in neutrophil-associated cytokines interleukin 8 (IL-8) and interleukin 6, and general inflammatory cytokines IFN-inducible protien-19, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin 1β, interleukin 10, and tumor necrosis factor, were identified both at first measurement and across hospitalization (P < .0001). COVID-19 neutrophils had exaggerated oxidative burst (P < .0001), NETosis (P < .0001), and phagocytosis (P < .0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected lungs available for examination (2 of 5). While elevations in IL-8 and absolute neutrophil count correlated with disease severity, plasma IL-8 levels alone correlated with death.
CONCLUSIONS
Literature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. Importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data show that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst.

Identifiants

DOI: 10.1093/cid/ciab437 PMID: 33988226 PMC: PMC8241438
pubmed: 33988226
pii: 6275596
doi: 10.1093/cid/ciab437
pmc: PMC8241438
doi:

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

479-489

Subventions

Organisme : NIAID NIH HHS
ID : R25 AI147376
Pays : United States
Organisme : BLRD VA
ID : I01 BX004767
Pays : United States
Organisme : NHLBI NIH HHS
ID : T32 HL134632
Pays : United States
Organisme : NCATS NIH HHS
ID : KL2 TR001444
Pays : United States
Organisme : NIAID NIH HHS
ID : K99 AI145762
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI135193
Pays : United States
Organisme : NHLBI NIH HHS
ID : K24 HL155884
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL137052
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI142742
Pays : United States

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Published by Oxford University Press for the Infectious Diseases Society of America 2021.

Auteurs

Jorge A Masso-Silva (JA)

Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.

Alexander Moshensky (A)

Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.

Michael T Y Lam (MTY)

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
The Salk Institute, La Jolla, California, USA.

Mazen F Odish (MF)

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.

Arjun Patel (A)

Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.

Le Xu (L)

Department of Pediatrics, University of California, San Diego , La Jolla, California, USA.

Emily Hansen (E)

Rady Children's Hospital, San Diego, California, USA.
Department of Pediatrics, University of California, San Diego , La Jolla, California, USA.

Samantha Trescott (S)

Rady Children's Hospital, San Diego, California, USA.
Department of Pediatrics, University of California, San Diego , La Jolla, California, USA.

Celina Nguyen (C)

Rady Children's Hospital, San Diego, California, USA.
Department of Pediatrics, University of California, San Diego , La Jolla, California, USA.

Roy Kim (R)

Rady Children's Hospital, San Diego, California, USA.
Department of Pediatrics, University of California, San Diego , La Jolla, California, USA.

Katherine Perofsky (K)

Rady Children's Hospital, San Diego, California, USA.
Department of Pediatrics, University of California, San Diego , La Jolla, California, USA.

Samantha Perera (S)

Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.

Lauren Ma (L)

Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.

Josephine Pham (J)

Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.

Mark Rolfsen (M)

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.

Jarod Olay (J)

Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.

John Shin (J)

Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.

Jennifer M Dan (JM)

Division of Infectious Diseases and Global Public Heath, Department of Medicine, University of California, San Diego , La Jolla, California, USA.
La Jolla Institute for Immunology, La Jolla, California, USA.

Robert K Abbott (RK)

Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla , CA 92037, USA.
Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute, La Jolla , CA 92037, USA.

Sydney Ramirez (S)

Division of Infectious Diseases and Global Public Heath, Department of Medicine, University of California, San Diego , La Jolla, California, USA.
La Jolla Institute for Immunology, La Jolla, California, USA.

Thomas H Alexander (TH)

Division of Head and Neck Surgery, Scripps Clinic , La Jolla, California, USA.

Grace Y Lin (GY)

Department of Pathology, University of California, San Diego , La Jolla, California, USA.

Ana Lucia Fuentes (AL)

Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.

Ira Advani (I)

Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.

Deepti Gunge (D)

Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.

Victor Pretorius (V)

Division of Cardiovascular and Thoracic Surgery, Department of Surgery, University of California, San Diego, La Jolla, California, USA.

Atul Malhotra (A)

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.

Xin Sun (X)

Department of Pediatrics, University of California, San Diego , La Jolla, California, USA.

Jason Duran (J)

Division of Cardiology, Department of Medicine, University of California, San Diego , La Jolla, California, USA.

Mark Hepokoski (M)

Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.

Shane Crotty (S)

Division of Infectious Diseases and Global Public Heath, Department of Medicine, University of California, San Diego , La Jolla, California, USA.
La Jolla Institute for Immunology, La Jolla, California, USA.

Nicole G Coufal (NG)

Rady Children's Hospital, San Diego, California, USA.
Department of Pediatrics, University of California, San Diego , La Jolla, California, USA.

Angela Meier (A)

Department of Anesthesiology, Division of Critical Care, University of California, San Diego , La Jolla, California, USA.

Laura E Crotty Alexander (LE)

Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.

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Classifications MeSH

questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › Increased Peripheral Blood Neutrophil...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Maladie grave › Increased Peripheral Blood Neutrophil...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace extracellulaire › Pièges extracellulaires › Increased Peripheral Blood Neutrophil...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Increased Peripheral Blood Neutrophil...
questionsmedicales.fr › Phénomènes du système immunitaire › Activation des neutrophiles › Increased Peripheral Blood Neutrophil...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Granulocytes neutrophiles › Increased Peripheral Blood Neutrophil...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › Increased Peripheral Blood Neutrophil...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN à brin positif › Nidovirales › Coronaviridae › Coronavirus › Betacoronavirus › Virus du SRAS › SARS-CoV-2 › Increased Peripheral Blood Neutrophil...