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

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME
Key Points

Question  What is the role of neutrophil extracellular traps in coronary thrombosis in patients with coronavirus disease 2019 (COVID-19) and myocardial infarction?

Findings  This case series report demonstrated a high burden of neutrophil extracellular traps (median density, 61%) in the coronary thrombi of 5 patients with ST-elevated myocardial infarction and COVID-19, compared with a historical series of 50 patients without COVID-19 (median NET density, 19%), which was a significant difference.

Meaning  Targeting intravascular neutrophil extracellular traps might be a relevant goal of treatment and a feasible way to prevent coronary thrombosis in patients with severe COVID-19.


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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Article Information

Accepted for Publication: December 2, 2020.

Published Online: December 29, 2020. doi:10.1001/jamacardio.2020.7308

Corresponding Author: Ana Blasco, MD, PhD, Cardiology Department, Hospital Universitario Puerta de Hierro–Majadahonda, C/Manuel de Falla 1, 28222 Majadahonda, Madrid, Spain (ablasc@gmail.com).

Author Contributions: Dr Blasco had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Blasco, Goicolea, Del Trigo, Ortega, Silva, Bellas.

Acquisition, analysis, or interpretation of data: Blasco, Coronado, Hernandez-Terciado, Martín, Royuela, Ramil, García, Goicolea, Escudier, Bellas.

Drafting of the manuscript: Blasco, Ramil, García, Del Trigo, Silva.

Critical revision of the manuscript for important intellectual content: Coronado, Hernandez-Terciado, Martín, Royuela, Goicolea, Ortega, Escudier, Bellas.

Statistical analysis: Blasco, Royuela.

Obtained funding: Blasco.

Administrative, technical, or material support: Coronado, Hernandez-Terciado, Martín, Royuela, Ramil, García, Del Trigo, Ortega, Escudier.

Supervision: Royuela, Goicolea, Silva, Bellas.

Conflict of Interest Disclosures: None reported.

Funding/Support: This work was supported by a grant of the Spanish Society of Cardiology.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: The authors wish to thank the donors and the Biobank Hospital Universitario Puerta de Hierro–Majadahonda and Instituto de Investigación Sanitaria Puerta de Hierro–Segovia de Arana (PT17/0015/0020 in the Spanish National Biobanks Network) for the human specimens used in this study. Our sincere thanks to the staff members and the nursing team at the Interventional Cardiology Unit, who collected the patient samples, and the cardiology physicians on duty at the Coronary Unit, who participated in the compilation of the clinical information of patients. This work had not been possible without their invaluable assistance.

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