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. 2021 Apr 1;6(4):469-474.
doi: 10.1001/jamacardio.2020.7308.

Assessment of Neutrophil Extracellular Traps in Coronary Thrombus of a Case Series of Patients With COVID-19 and Myocardial Infarction

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Assessment of Neutrophil Extracellular Traps in Coronary Thrombus of a Case Series of Patients With COVID-19 and Myocardial Infarction

Ana Blasco et al. JAMA Cardiol. .

Abstract

Importance: Severe coronavirus disease 2019 (COVID-19) is characterized by the intense formation of neutrophil extracellular traps (NETs), leading to the occlusion of microvessels, as shown in pulmonary samples. The occurrence of ST-elevated myocardial infarction (STEMI) is a serious cardiac manifestation of COVID-19; the intrinsic mechanism of coronary thrombosis appears to still be unknown.

Objective: To determine the role of NETs in coronary thrombosis in patients with COVID-19.

Design, setting, and participants: This was a consecutive series of patients with COVID-19 at an academic tertiary hospital in Madrid, Spain, who underwent primary coronary interventions for STEMI in which coronary aspirates were obtained in the catheterization laboratory using a thrombus aspiration device. Patients with COVID-19 who experienced a STEMI between March 23 and April 11, 2020, from whom coronary thrombus samples were aspirated during primary coronary intervention, were included in the analysis. These patients were compared with a series conducted from July 2015 to December 2015 of patients with STEMI.

Main outcomes and measures: The presence and quantity of NETs in coronary aspirates from patients with STEMI and COVID-19. The method for the analysis of NETs in paraffin-embedded coronary thrombi was based on the use of confocal microscopy technology and image analysis for the colocalization of myeloperoxidase-DNA complexes and citrullinated histone H3. Immunohistochemical analysis of thrombi was also performed. Clinical and angiographic variables were prospectively collected.

Results: Five patients with COVID-19 were included (4 men [80%]; mean [SD] age, 62 [14] years); the comparison group included 50 patients (44 males [88%]; mean [SD] age, 58 [12] years). NETs were detected in the samples of all 5 patients with COVID-19, and the median density of NETs was 61% (95% CI, 43%-91%). In the historical series of patients with STEMI, NETs were found in 34 of 50 thrombi (68%), and the median NET density was 19% (95% CI, 13%-22%; P < .001). All thrombi from patients with COVID-19 were composed of fibrin and polymorphonuclear cells. None of them showed fragments of atherosclerotic plaque or iron deposits indicative of previous episodes of plaque rupture.

Conclusions and relevance: In this small case series of patients with COVID-19 and myocardial infarction, NETs seem to play a major role in the pathogenesis of STEMI in COVID-19 disease. Our findings support the idea that targeting intravascular NETs might be a relevant goal of treatment and a feasible way to prevent coronary thrombosis in patients with severe COVID-19 disease.

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Conflict of interest statement

Conflict of Interest Disclosures: None reported.

Figures

Figure.
Figure.. Immunofluorescence of Neutrophil Extracellular Traps in Thrombi Aspirated During Primary Coronary Intervention in Patients With ST-Elevated Myocardial Infarction
A-D, Representative images of the coronary aspirate from a patient with ST-elevated myocardial infarction and coronavirus disease 2019. E-H, Representative images of coronary aspirate from a patient with ST-elevated myocardial infarction without coronavirus disease 2019. A and E, DNA stained with TO-PRO for the identification of nuclei. B and F, Neutrophils stained with myeloperoxidase-specific antibody. C and G, Sample stained with citrullinated histone H3–specific antibody. D, Merger of the 3 labels confirms the presence of extracellular traps by colocalization of myeloperoxidase and citrullinated histone H3. H, Merger of the 3 labels showing neutrophil extracellular traps to a lesser extent than in sample D. Bars represent 50 μm.

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