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

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. This case series study reports formation of neutrophil extracellular traps in 5 patients with coronavirus disease 2019 with ST-elevated myocardial infarction and compares findings with 50 patients who had experienced myocardial infarction before the coronavirus disease 2019 pandemic. 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.

Automated summary

Severe COVID-19 can lead to intense formation of neutrophil extracellular traps (NETs) which occlude microvessels, potentially causing ST-elevated myocardial infarction. In patients with COVID-19, a higher density of NETs was found in coronary thrombi compared to historical patients without COVID-19, suggesting a role of NETs in coronary thrombosis pathogenesis. Targeting intravascular NETs could be a relevant treatment goal for preventing coronary thrombosis in severe COVID-19 cases.