Association of Neutrophil Activation, More Than Platelet Activation, With Thrombotic Complications in Coronavirus Disease 2019.

Abstract

BACKGROUND:

Severe acute respiratory syndrome coronavirus 2 infection is associated with hypercoagulability, which predisposes to venous thromboembolism (VTE). We analyzed platelet and neutrophil activation in patients with coronavirus disease 2019 (COVID-19) and their association with VTE.

METHODS:

Hospitalized patients with COVID-19 and age- and sex-matched healthy controls were studied. Platelet and leukocyte activation, neutrophil extracellular traps (NETs), and matrix metalloproteinase 9, a neutrophil-released enzyme, were measured. Four patients were restudied after recovery. The activating effect of plasma from patients with COVID-19 on control platelets and leukocytes and the inhibiting activity of common antithrombotic agents on it were studied.

RESULTS:

A total of 36 patients with COVID-19 and 31 healthy controls were studied; VTE developed in 8 of 36 patients with COVID-19 (22.2%). Platelets and neutrophils were activated in patients with COVID-19. NET, but not platelet activation, biomarkers correlated with disease severity and were associated with thrombosis. Plasmatic matrix metalloproteinase 9 was significantly increased in patients with COVID-19. Platelet and neutrophil activation markers, but less so NETs, normalized after recovery. In vitro, plasma from patients with COVID-19 triggered platelet and neutrophil activation and NET formation, the latter blocked by therapeutic-dose low-molecular-weight heparin, but not by aspirin or dypiridamole.

CONCLUSIONS:

Platelet and neutrophil activation are key features of patients with COVID-19. NET biomarkers may help to predict clinical worsening and VTE and may guide low-molecular-weight heparin treatment.

• Authors: Eleonora Petito, Emanuela Falcinelli, Ugo Paliani, Enrica Cesari, Gaetano Vaudo, Manuela Sebastiano, Vittorio Cerotto, Giuseppe Guglielmini, Fabio Gori, Marco Malvestiti, Cecilia Becattini, Francesco Paciullo, Edoardo De Robertis, Loredana Bury, Teseo Lazzarini, Paolo Gresele, COVIR study investigators
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 223 Issue 6 Pg. 933-944 (03 29 2021) ISSN: 1537-6613 [Electronic] United States
• PMID: 33280009 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: [email protected].

Chemical References

• Biomarkers
• Heparin, Low-Molecular-Weight
• Matrix Metalloproteinase 9

Topics

• Adult
• Aged
• Aged, 80 and over
• Biomarkers (blood)
• Blood Platelets (immunology)
• COVID-19 (blood, immunology, virology)
• Extracellular Traps
• Female
• Heparin, Low-Molecular-Weight (blood)
• Humans
• Male
• Matrix Metalloproteinase 9 (blood)
• Middle Aged
• Neutrophil Activation
• Neutrophils (immunology)
• Platelet Activation
• SARS-CoV-2 (isolation & purification)
• Thrombosis (blood, immunology, virology)
• Venous Thromboembolism (blood, immunology, virology)