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Targeting potential drivers of COVID-19: Neutrophil extracellular traps
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Coronavirus disease 2019 (COVID-19) is a novel, viral-induced respiratory disease that in ∼10–15% of patients progresses to acute respiratory distress syndrome (ARDS) triggered by a cytokine storm. In this Perspective, autopsy results and literature are presented supporting the hypothesis that a little known yet powerful function of neutrophils—the ability to form neutrophil extracellular traps (NETs)—may contribute to organ damage and mortality in COVID-19. We show lung infiltration of neutrophils in an autopsy specimen from a patient who succumbed to COVID-19. We discuss prior reports linking aberrant NET formation to pulmonary diseases, thrombosis, mucous secretions in the airways, and cytokine production. If our hypothesis is correct, targeting NETs directly and/or indirectly with existing drugs may reduce the clinical severity of COVID-19.
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“Excessive NETosis has been implicated in the development of cytokine storms and thrombosis.259”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [259]
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Metadata
- Authors
- Barnes, B. J., Adrover, J. M., Baxter-Stoltzfus, A., Borczuk, A., Cools-Lartigue, J., Crawford, J. M., Daßler-Plenker, J., Guerci, P., Huynh, C., Knight, J. S., Loda, M., Looney, M. R., McAllister, F., Rayes, R., Renaud, S., Rousseau, S., Salvatore, S., Schwartz, R. E., Spicer, J. D., Yost, C. C., Weber, A., Zuo, Y., & Egeblad, M.
- Affiliations
- Feinstein Institute for Medical Research (US)
- Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 2
- Weill Cornell Medicine (US)
- Division of Thoracic and Upper GI Surgery, Department of Surgery, Montreal, Canada 4
- Hofstra University (US)
- Centre Hospitalier Régional et Universitaire de Nancy (FR)
- McGill University (CA)
- University of Michigan (US)
- University of California, San Francisco (US)
- The University of Texas MD Anderson Cancer Center (US)
- Centre Hospitalier Universitaire de Nancy, Nancy, France 6
- Research Institute of the McGill University Health Centre (CA)
- University of Utah (US)
- Northwell Health (US)
- Cold Spring Harbor Laboratory (US)
- Corresponding author
- Barnes, Betsy J.
- Egeblad, Mikala
- ORCID
- Barnes, Betsy J.
- Baxter-Stoltzfus, Amelia
- Borczuk, Alain
- Crawford, James M.
- Guerci, Philippe
- Huynh, Caroline
- Knight, Jason S.
- Loda, Massimo
- Looney, Mark R.
- McAllister, Florencia
- Rayes, Roni
- Rousseau, Simon
- Salvatore, Steven
- Schwartz, Robert E.
- Spicer, Jonathan D.
- Yost, Christian C.
- Weber, Andrew
- Zuo, Yu
- Egeblad, Mikala
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2020-04-16
- Volume
- 217
- Issue
- 6
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC7161085
- OpenAlex
- W3016393661
- Cited by
- 1,486
- References
- 84
- Citations by year
- 2026: 34 · 2025: 70 · 2024: 124 · 2023: 150 · 2022: 288 · 2021: 438 · 2020: 378
- FWCI
- 110.17
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Experimental Medicine (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- eScholarship@McGill (McGill) (submittedVersion)
- Funders
- National Institutes of Health (5p30ca045508-35)
- National Heart, Lung, and Blood Institute (R01HL130324, R01HL134846)
- National Cancer Institute (P30-CA045508)
- National Institute of Allergy and Infectious Diseases (R01AI125445)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK121072)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR076242)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD093826)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Keywords
- COVID-19 pandemic, neutrophil extracellular traps, neutrophils, acute respiratory distress syndrome, cytokine storm, lung infiltration, organ damage, thrombosis, airway mucus secretion, targeted drug delivery, autopsy findings
- MeSH terms
- Betacoronavirus, COVID-19, SARS-CoV-2, Humans, Lung Diseases, Neutrophils, Pneumonia, Viral, Cytokines, Coronavirus Infections, Pandemics, Extracellular Traps
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