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[Preprint]. 2020 May 5:2020.04.30.20086736.
doi: 10.1101/2020.04.30.20086736.

Neutrophil extracellular traps and thrombosis in COVID-19

Yu Zuo, Melanie Zuo, Srilakshmi Yalavarthi, Kelsey Gockman, Jacqueline A Madison, Hui Shi, Wrenn Woodard, Sean P Lezak, Njira L Lugogo, Jason S Knight, Yogendra Kanthi

Neutrophil extracellular traps and thrombosis in COVID-19

Yu Zuo et al. medRxiv. .

Update in

  • Neutrophil extracellular traps in COVID-19.
    Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M, Madison JA, Blair C, Weber A, Barnes BJ, Egeblad M, Woods RJ, Kanthi Y, Knight JS. Zuo Y, et al. JCI Insight. 2020 Jun 4;5(11):e138999. doi: 10.1172/jci.insight.138999. JCI Insight. 2020. PMID: 32329756 Free PMC article.

Abstract

Background: Early studies of patients with COVID-19 have demonstrated markedly dysregulated coagulation and a high risk of morbid arterial and venous thrombotic events. While elevated levels of blood neutrophils and neutrophil extracellular traps (NETs) have been described in patients with COVID-19, their potential role in COVID-19-associated thrombosis remains unknown.

Objectives: To elucidate the potential role of hyperactive neutrophils and NET release in COVID-19-associated thrombosis.

Patients/methods: This is a retrospective, case-control study of patients hospitalized with COVID-19 who developed thrombosis (n=11), as compared with gender- and age-matched COVID-19 patients without clinical thrombosis (n=33). In addition to capturing clinical data, we measured remnants of NETs (cell-free DNA, myeloperoxidase-DNA complexes, and citrullinated histone H3) and neutrophil-derived S100A8/A9 (calprotectin) in patient sera.

Results: The majority of patients (9/11) were receiving at least prophylactic doses of heparinoids at the time thrombosis was diagnosed. As compared with controls, patients with COVID-19-associated thrombosis had significantly higher blood levels of markers of NETs (cell-free DNA, myeloperoxidase-DNA complexes, citrullinated histone H3) and neutrophil activation (calprotectin). The thrombosis group also had higher levels of D-dimer, CRP, ferritin, and platelets, but not troponin or neutrophils. Finally, there were strong associations between markers of hyperactive neutrophils (calprotectin and cell-free DNA) and D-dimer.

Conclusion: Elevated levels of neutrophil activation and NET formation in patients hospitalized with COVID-19 are associated with higher risk of morbid thrombotic complications. These observations underscore the need for urgent investigation into the potential relationship between NETs and unrelenting thrombosis in COVID-19.

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