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Comparative Study
. 2021 Feb;51(2):446-453.
doi: 10.1007/s11239-020-02324-z. Epub 2020 Nov 5.

Neutrophil extracellular traps and thrombosis in COVID-19

Yu Zuo  1 , Melanie Zuo  2 , Srilakshmi Yalavarthi  1 , Kelsey Gockman  1 , Jacqueline A Madison  1 , Hui Shi  1   3 , Wrenn Woodard  4 , Sean P Lezak  4 , Njira L Lugogo  5 , Jason S Knight  6 , Yogendra Kanthi  7   8
Affiliations
Comparative Study

Neutrophil extracellular traps and thrombosis in COVID-19

Yu Zuo et al. J Thromb Thrombolysis. 2021 Feb.

Abstract

Studies of patients with COVID-19 have demonstrated markedly dysregulated coagulation and a high risk of morbid arterial and venous thrombotic events. Elevated levels of blood neutrophils and neutrophil extracellular traps (NETs) have recently been described in patients with COVID-19. However, their potential role in COVID-19-associated thrombosis remains incompletely understood. In order to elucidate the potential role of hyperactive neutrophils and NET release in COVID-19-associated thrombosis, we conducted a case-control study of patients hospitalized with COVID-19 who developed thrombosis, as compared with gender- and age-matched COVID-19 patients without clinical thrombosis. We found that remnants of NETs (cell-free DNA, myeloperoxidase-DNA complexes, and citrullinated histone H3) and neutrophil-derived S100A8/A9 (calprotectin) in patient sera were associated with higher risk of morbid thrombotic events in spite of prophylactic anticoagulation. These observations underscore the need for urgent investigation into the potential relationship between NETs and unrelenting thrombosis in COVID-19, as well as novel approaches for thrombosis prevention.

Keywords: Blood coagulation; COVID-19; Calprotectin; Extracellular traps; Neutrophils; Venous thrombosis.

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Conflict of interest statement

YK has received consulting fees from Surface Oncology, and has a pending patent on the use of biogases in vascular disease. JSK has received grant support from Jazz Pharmaceuticals.

Figures

Fig. 1
Fig. 1
Elevated levels of NETs in the blood of COVID-19 patients diagnosed with a thrombotic event, as compared with matched controls. Serum was tested for calprotectin (a), cell-free DNA (b), myeloperoxidase-DNA complexes (c), and citrullinated histone H3 (d). N = 33 for the control group and n = 11 for the thrombosis group. Comparisons were by Mann–Whitney test; *p < 0.05, **p < 0.01, and ***p < 0.001
Fig. 2
Fig. 2
Association between peak levels of clinical biomarkers and diagnosis of a thrombotic event. Clinical testing is reported for D-dimer (a), troponin (b), C-reactive protein (c), ferritin (d), absolute neutrophil count (e), and absolute platelet count (f). N = 33 for the control group and n = 11 for the thrombosis group. Comparisons were by Mann–Whitney test; *p < 0.05 and **p < 0.01. Comparisons for peak troponin and peak neutrophil count were not statistically significant
Fig. 3
Fig. 3
Correlation between neutrophil activation markers and D-dimer. Calprotectin (a) and cell-free DNA (b) were compared to peak D-dimer levels. Data were analyzed by Pearson’s method
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