Coronavirus Disease 2019 (COVID-19) Coronary Vascular Thrombosis: Correlation with Neutrophil but Not Endothelial Activation

• Main Authors: Jane-Wit, D. (Author), Johnson, J.E (Author), Libby, P. (Author), McGuone, D. (Author), Mitchell, R.N (Author), Pober, J.S (Author), Xu, M.L (Author)
• Format: Article
• Language: English
• Published: Elsevier Inc. 2022
• Subjects: adult; aged; Aged; Aged, 80 and over; anticoagulant agent; anticoagulant therapy; Article; autopsy; Blood Platelets; blood vessel; cardiac muscle; cardiovascular disease; cell activation; cell death; clinical article; cohort analysis; controlled study; coronary artery thrombosis; coronary blood vessel; Coronary Vessels; coronavirus disease 2019; correlational study; COVID-19; endothelium; Endothelium, Vascular; extracellular trap; female; Female; fluorescence microscopy; gene expression; gene expression regulation; Gene Expression Regulation; heart tissue; human; human cell; human tissue; Humans; ICAM 1 gene; immunofluorescence; intercellular adhesion molecule 1; leukocyte activation; male; Male; metabolism; middle aged; Middle Aged; mortality; myocarditis; Myocarditis; Myocardium; neutrophil; Neutrophil Activation; Neutrophils; pandemic; pathology; Platelet Aggregation; RelA gene; SARS-CoV-2; STAT1 gene; STAT1 protein; STAT3 gene; STAT3 protein; TF gene; thrombocyte; thrombocyte aggregation; thromboplastin; thrombosis; Thrombosis; transcription factor RelA; vascular cell adhesion molecule 1; vascular endothelium; very elderly; von Willebrand factor; VWF gene
• Online Access: View Fulltext in Publisher

 Severe coronavirus disease 2019 (COVID-19) increases the risk of myocardial injury that contributes to mortality. This study used multiparameter immunofluorescence to extensively examine heart autopsy tissue of 7 patients who died of COVID-19 compared to 12 control specimens, with or without cardiovascular disease. Consistent with prior reports, no evidence of viral infection or lymphocytic infiltration indicative of myocarditis was found. However, frequent and extensive thrombosis was observed in large and small vessels in the hearts of the COVID-19 cohort, findings that were infrequent in controls. The endothelial lining of thrombosed vessels typically lacked evidence of cytokine-mediated endothelial activation, assessed as nuclear expression of transcription factors p65 (RelA), pSTAT1, or pSTAT3, or evidence of inflammatory activation assessed by expression of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tissue factor, or von Willebrand factor (VWF). Intimal EC lining was also generally preserved with little evidence of cell death or desquamation. In contrast, there were frequent markers of neutrophil activation within myocardial thrombi in patients with COVID-19, including neutrophil-platelet aggregates, neutrophil-rich clusters within macrothrombi, and evidence of neutrophil extracellular trap (NET) formation. These findings point to alterations in circulating neutrophils rather than in the endothelium as contributors to the increased thrombotic diathesis in the hearts of COVID-19 patients. © 2022 American Society for Investigative Pathology