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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.
Masso-Silva, Jorge A; Moshensky, Alexander; Lam, Michael T Y; Odish, Mazen F; Patel, Arjun; Xu, Le; Hansen, Emily; Trescott, Samantha; Nguyen, Celina; Kim, Roy; Perofsky, Katherine; Perera, Samantha; Ma, Lauren; Pham, Josephine; Rolfsen, Mark; Olay, Jarod; Shin, John; Dan, Jennifer M; Abbott, Robert K; Ramirez, Sydney; Alexander, Thomas H; Lin, Grace Y; Fuentes, Ana Lucia; Advani, Ira; Gunge, Deepti; Pretorius, Victor; Malhotra, Atul; Sun, Xin; Duran, Jason; Hepokoski, Mark; Crotty, Shane; Coufal, Nicole G; Meier, Angela; Crotty Alexander, Laura E.
  • Masso-Silva JA; Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
  • Moshensky A; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
  • Lam MTY; Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
  • Odish MF; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
  • Patel A; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
  • Xu L; The Salk Institute, La Jolla, California, USA.
  • Hansen E; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
  • Trescott S; Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
  • Nguyen C; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
  • Kim R; Department of Pediatrics, University of California, San Diego , La Jolla, California, USA.
  • Perofsky K; Rady Children's Hospital, San Diego, California, USA.
  • Perera S; Department of Pediatrics, University of California, San Diego , La Jolla, California, USA.
  • Ma L; Rady Children's Hospital, San Diego, California, USA.
  • Pham J; Department of Pediatrics, University of California, San Diego , La Jolla, California, USA.
  • Rolfsen M; Rady Children's Hospital, San Diego, California, USA.
  • Olay J; Department of Pediatrics, University of California, San Diego , La Jolla, California, USA.
  • Shin J; Rady Children's Hospital, San Diego, California, USA.
  • Dan JM; Department of Pediatrics, University of California, San Diego , La Jolla, California, USA.
  • Abbott RK; Rady Children's Hospital, San Diego, California, USA.
  • Ramirez S; Department of Pediatrics, University of California, San Diego , La Jolla, California, USA.
  • Alexander TH; Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
  • Lin GY; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
  • Fuentes AL; Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
  • Advani I; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
  • Gunge D; Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
  • Pretorius V; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
  • Malhotra A; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
  • Sun X; Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
  • Duran J; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
  • Hepokoski M; Pulmonary and Critical Care Section, Veterans Affairs San Diego Healthcare System, La Jolla, California, USA.
  • Crotty S; Division of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of California, San Diego, La Jolla, California, USA.
  • Coufal NG; Division of Infectious Diseases and Global Public Heath, Department of Medicine, University of California, San Diego , La Jolla, California, USA.
  • Meier A; La Jolla Institute for Immunology, La Jolla, California, USA.
  • Crotty Alexander LE; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI), La Jolla , CA 92037, USA.
Clin Infect Dis ; 74(3): 479-489, 2022 02 11.
Article in English | MEDLINE | ID: covidwho-1228461
Semantic information from SemMedBD (by NLM)
1. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
2. Neutrophil Activation PROCESS_OF Patients
Subject
Neutrophil Activation
Predicate
PROCESS_OF
Object
Patients
3. Inflammation COEXISTS_WITH COVID-19
Subject
Inflammation
Predicate
COEXISTS_WITH
Object
COVID-19
4. Respiratory Distress Syndrom COEXISTS_WITH C5203670
Subject
Respiratory Distress Syndrom
Predicate
COEXISTS_WITH
Object
C5203670
5. Inflammatory disorder COEXISTS_WITH COVID-19
Subject
Inflammatory disorder
Predicate
COEXISTS_WITH
Object
COVID-19
6. Infection COEXISTS_WITH COVID-19
Subject
Infection
Predicate
COEXISTS_WITH
Object
COVID-19
7. COVID-19 CAUSES Disease
Subject
COVID-19
Predicate
CAUSES
Object
Disease
8. TNF STIMULATES interleukin-8
Subject
TNF
Predicate
STIMULATES
Object
interleukin-8
9. Granulocyte-Macrophage Colony-Stimulating Factor|CSF2|LAMC2 STIMULATES interleukin-6
Subject
Granulocyte-Macrophage Colony-Stimulating Factor|CSF2|LAMC2
Predicate
STIMULATES
Object
interleukin-6
10. Granulocyte-Macrophage Colony-Stimulating Factor|CSF2|LAMC2 STIMULATES interleukin-8
Subject
Granulocyte-Macrophage Colony-Stimulating Factor|CSF2|LAMC2
Predicate
STIMULATES
Object
interleukin-8
11. interleukin-10 STIMULATES interleukin-8
Subject
interleukin-10
Predicate
STIMULATES
Object
interleukin-8
12. IL1B gene|IL1B STIMULATES interleukin-6
Subject
IL1B gene|IL1B
Predicate
STIMULATES
Object
interleukin-6
13. IL1B gene|IL1B STIMULATES interleukin-8
Subject
IL1B gene|IL1B
Predicate
STIMULATES
Object
interleukin-8
14. interleukin-10 STIMULATES interleukin-6
Subject
interleukin-10
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STIMULATES
Object
interleukin-6
15. TNF STIMULATES interleukin-6
Subject
TNF
Predicate
STIMULATES
Object
interleukin-6
16. Parenchyma PART_OF Lung
Subject
Parenchyma
Predicate
PART_OF
Object
Lung
17. Parenchyma LOCATION_OF Leukocytosis
Subject
Parenchyma
Predicate
LOCATION_OF
Object
Leukocytosis
18. Airway structure LOCATION_OF SPINK5 gene|SPINK5
Subject
Airway structure
Predicate
LOCATION_OF
Object
SPINK5 gene|SPINK5
19. Alveolus LOCATION_OF SPINK5 gene|SPINK5
Subject
Alveolus
Predicate
LOCATION_OF
Object
SPINK5 gene|SPINK5
20. Plasma LOCATION_OF interleukin-8
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Plasma
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LOCATION_OF
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interleukin-8
21. Lung PART_OF Patients
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Lung
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Patients
22. COVID-19 PROCESS_OF Patients
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COVID-19
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PROCESS_OF
Object
Patients
23. Neutrophil Activation PROCESS_OF Patients
Subject
Neutrophil Activation
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PROCESS_OF
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Patients
24. Inflammation COEXISTS_WITH COVID-19
Subject
Inflammation
Predicate
COEXISTS_WITH
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COVID-19
25. Respiratory Distress Syndrome, Adult COEXISTS_WITH COVID-19
Subject
Respiratory Distress Syndrome, Adult
Predicate
COEXISTS_WITH
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COVID-19
26. Inflammatory disorder COEXISTS_WITH COVID-19
Subject
Inflammatory disorder
Predicate
COEXISTS_WITH
Object
COVID-19
27. Infection COEXISTS_WITH COVID-19
Subject
Infection
Predicate
COEXISTS_WITH
Object
COVID-19
28. COVID-19 CAUSES Disease
Subject
COVID-19
Predicate
CAUSES
Object
Disease
29. TNF STIMULATES interleukin-8
Subject
TNF
Predicate
STIMULATES
Object
interleukin-8
30. Granulocyte-Macrophage Colony-Stimulating Factor|CSF2|LAMC2 STIMULATES interleukin-6
Subject
Granulocyte-Macrophage Colony-Stimulating Factor|CSF2|LAMC2
Predicate
STIMULATES
Object
interleukin-6
31. Granulocyte-Macrophage Colony-Stimulating Factor|CSF2|LAMC2 STIMULATES interleukin-8
Subject
Granulocyte-Macrophage Colony-Stimulating Factor|CSF2|LAMC2
Predicate
STIMULATES
Object
interleukin-8
32. interleukin-10 STIMULATES interleukin-8
Subject
interleukin-10
Predicate
STIMULATES
Object
interleukin-8
33. IL1B gene|IL1B STIMULATES interleukin-6
Subject
IL1B gene|IL1B
Predicate
STIMULATES
Object
interleukin-6
34. IL1B gene|IL1B STIMULATES interleukin-8
Subject
IL1B gene|IL1B
Predicate
STIMULATES
Object
interleukin-8
35. interleukin-10 STIMULATES interleukin-6
Subject
interleukin-10
Predicate
STIMULATES
Object
interleukin-6
36. TNF STIMULATES interleukin-6
Subject
TNF
Predicate
STIMULATES
Object
interleukin-6
37. Parenchyma PART_OF Lung
Subject
Parenchyma
Predicate
PART_OF
Object
Lung
38. Parenchyma LOCATION_OF Leukocytosis
Subject
Parenchyma
Predicate
LOCATION_OF
Object
Leukocytosis
39. Airway structure LOCATION_OF SPINK5 gene|SPINK5
Subject
Airway structure
Predicate
LOCATION_OF
Object
SPINK5 gene|SPINK5
40. Alveolus LOCATION_OF SPINK5 gene|SPINK5
Subject
Alveolus
Predicate
LOCATION_OF
Object
SPINK5 gene|SPINK5
41. Plasma LOCATION_OF interleukin-8
Subject
Plasma
Predicate
LOCATION_OF
Object
interleukin-8
42. Lung PART_OF Patients
Subject
Lung
Predicate
PART_OF
Object
Patients
ABSTRACT

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 1ß, 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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Extracellular Traps / COVID-19 Type of study: Prognostic study / Reviews Limits: Humans Language: English Journal: Clin Infect Dis Journal subject: Communicable Diseases Year: 2022 Document Type: Article Affiliation country: Cid

Full text: Available Collection: International databases Database: MEDLINE Main subject: Extracellular Traps / COVID-19 Type of study: Prognostic study / Reviews Limits: Humans Language: English Journal: Clin Infect Dis Journal subject: Communicable Diseases Year: 2022 Document Type: Article Affiliation country: Cid