Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 May 20;22(10):5368.
doi: 10.3390/ijms22105368.

The Emerging Role of Neutrophils in the Pathogenesis of Thrombosis in COVID-19

Valeria Iliadi  1 , Ina Konstantinidou  2 , Konstantina Aftzoglou  3 , Sergios Iliadis  1 , Theocharis G Konstantinidis  4 , Christina Tsigalou  5
Affiliations
Review

The Emerging Role of Neutrophils in the Pathogenesis of Thrombosis in COVID-19

Valeria Iliadi et al. Int J Mol Sci. .

Abstract

Previous studies have shown that COVID-19 leads to thrombotic complications, which have been associated with high morbidity and mortality rates. Neutrophils are the largest population of white blood cells and play a pivotal role in innate immunity. During an infection, neutrophils migrate from circulation to the infection site, contributing to killing pathogens. This mechanism is regulated by chemokines such as IL-8. Moreover, it was shown that neutrophils play an important role in thromboinflammation. Through a diverse repertoire of mechanisms, neutrophils, apart from directly killing pathogens, are able to activate the formation of thrombi. In COVID-19 patients, neutrophil activation promotes neutrophil extracellular trap (NET) formation, platelet aggregation, and cell damage. Furthermore, neutrophils participate in the pathogenesis of endothelitis. Overall, this review summarizes recent progress in research on the pathogenesis of COVID-19, highlighting the role of the prothrombotic action of neutrophils in NET formation.

Keywords: COVID-19; NETs; SARS CoV-2; immunothrombosis.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Neutrophil and thromboinflammation in COVID-19. Host–virus interplay includes virus-related alveolar macrophage activation, which leads to a cascade of inflammatory stimuli, cell activation, and migration. Signals from different chemokines induce neutrophil–endothelium interactions, allowing neutrophil to crawl and arrest along the endothelium. Neutrophils accomplish their extravasation predominantly via endothelial cell–cell junctions. At the site of infection, neutrophils activate phagocytosis, degranulation, and NET formation, which can protect the host during its virus response. On the other hand, neutrophils can exacerbate lung hyperinflammation and cytokine storm in COVID-19 patients. Ultimately, NETs interact with the platelets and complements, thereby causing endothelial cell damage and triggering thrombi formation. Hyperinflammation and Inflammatory microvascular thrombi then lead to system inflammation, which affects kidney, gut, liver, and heart function. Abbreviations: SARS-CoV-2: severe acute respiratory syndrome coronavirus 2; PAMP: pathogen-associated molecular pattern; DAMP: danger-associated molecular pattern; NETs: neutrophil extracellular traps.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Zhu N., Zhang D., Wang W., Li X., Yang B., Song J., Zhao X., Huang B., Shi W., Lu R., et al. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N. Engl. J. Med. 2020;382:727–733. doi: 10.1056/NEJMoa2001017. - DOI - PMC - PubMed
    1. WHO Coronavirus (COVID-19) Dashboard. [(accessed on 28 March 2021)]; Available online: https://covid19.who.int.
    1. Guo Y.-R., Cao Q.-D., Hong Z.-S., Tan Y.-Y., Chen S.-D., Jin H.-J., Tan K.-S., Wang D.-Y., Yan Y. The Origin, Transmission and Clinical Therapies on Coronavirus Disease 2019 (COVID-19) Outbreak-an Update on the Status. Mil Med. Res. 2020;7:11. doi: 10.1186/s40779-020-00240-0. - DOI - PMC - PubMed
    1. Zuo Y., Yalavarthi S., Shi H., Gockman K., Zuo M., Madison J.A., Blair C., Weber A., Barnes B.J., Egeblad M., et al. Neutrophil Extracellular Traps in COVID-19. JCI Insight. 2020;5:e138999. doi: 10.1172/jci.insight.138999. - DOI - PMC - PubMed
    1. Ibañez C., Perdomo J., Calvo A., Ferrando C., Reverter J.C., Tassies D., Blasi A. High D Dimers and Low Global Fibrinolysis Coexist in COVID19 Patients: What Is Going on in There? J. Thromb. Thrombolysis. 2020;51:308–312. doi: 10.1007/s11239-020-02226-0. - DOI - PMC - PubMed

MeSH terms