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

Abstract

IMPORTANCESevere coronavirus disease 2019 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 MEASURESThe 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. RESULTSFive 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 RELEVANCEIn 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.

SARS-COV-2 colonizes coronary thrombus and impairs heart microcirculation bed in asymptomatic SARS-CoV-2 positive subjects with acute myocardial infarction

“…Moreover, patient selection is in accordance with the routine clinical practice, as patients underwent thrombus aspiration based on 2017 AHA guidelines [ 36 ] and ESC 2017 [ 37 ] to manage the patient with STEMI. Accordingly, the percentage of patients undergoing thrombus aspiration in our study (176 of 474, 37%) agrees with previous and more numerous observational studies [ 36 – 39 ]. Another limitation of the study was the not fully evaluation of inflammatory markers as pro-inflammatory cytokines.…”

Circulating Calprotectin as a Biomarker of COVID-19 Severity

“…Preliminary data indicate that SARS-CoV-2 can activate NETosis in human neutrophils, potentially due to increased levels of intracellular Reactive Oxygen Species (ROS) [95]. Besides thrombosis, NETosis has also been associated with ST-elevated myocardial infarction (STEMI) in COVID-19 disease [96]. All these data point to a crucial role of NET formation leading to severe pulmonary complications of COVID-19.…”

“…All these data point to a crucial role of NET formation leading to severe pulmonary complications of COVID-19. Based on the growing evidence about the involvement of NETs in the pathogenesis of COVID-19, NET inhibitors have been proposed and are being studied as a feasible way to prevent coronary thrombosis in patients with severe COVID-19 disease [95][96][97][98]. Several intervention trials are currently recruiting with a diversity of study designs and outcome measures.…”

COVID‐19 and immunothrombosis: emerging understanding and clinical management

“…34 Additionally, a small case series of COVID-19 patients undergoing primary coronary interventions for ST elevation MI showed neutrophil extracellular traps (NETs) formation in 68% of thrombi. 35 In addition to larger vessel thromboses, examination of the lung and cutaneous tissue autopsy samples from patients who died from severe COVID-19 infection and respiratory failure demonstrates the presence of microvascular injury with thrombosis. 36,37 Diffuse inflammatory alveolar change with macrophage infiltration has been reported in early pathological studies of patients with COVID-19 pneumonia, alongside extensive vascular congestion.…”

“…A large study of 3334 hospitalised COVID‐19 patients demonstrated MI was the commonest thrombotic event in their cohort, occurring in 8·9% of patients 34 . Additionally, a small case series of COVID‐19 patients undergoing primary coronary interventions for ST elevation MI showed neutrophil extracellular traps (NETs) formation in 68% of thrombi 35 …”