Neutrophils predominate the immune signature of cerebral thrombi in COVID-19 stroke patients

• Published in: Acta neuropathologica communications 2022-02, Vol.10 (1), p.14-14, Article 14
• Main Authors: Genchi, Angela, Semerano, Aurora, Schwarz, Ghil, Dell'Acqua, Beatrice, Gullotta, Giorgia Serena, Sampaolo, Michela, Boeri, Enzo, Quattrini, Angelo, Sanvito, Francesca, Diamanti, Susanna, Bergamaschi, Andrea, Grassi, Stefano, Podini, Paola, Panni, Pietro, Michelozzi, Caterina, Simionato, Franco, Scomazzoni, Francesco, Remida, Paolo, Valvassori, Luca, Falini, Andrea, Ferrarese, Carlo, Michel, Patrik, Saliou, Guillaume, Hajdu, Steven, Beretta, Simone, Roveri, Luisa, Filippi, Massimo, Strambo, Davide, Martino, Gianvito, Bacigaluppi, Marco
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Algorithms; Angiotensin-Converting Enzyme 2 - blood; Angiotensin-Converting Enzyme 2 - genetics; Angiotensin-Converting Enzyme 2 - immunology; Blood clot; Blood clots; Brain Ischemia - blood; Brain Ischemia - genetics; Brain Ischemia - immunology; Cloning; Coronaviruses; COVID-19; COVID-19 - blood; COVID-19 - genetics; COVID-19 - immunology; Cytokines; Disease transmission; Dyspnea; Endovascular treatment; Female; Fibrin; Health aspects; Histology; Hospitals; Humans; Immunity, Cellular - physiology; Infections; Intracranial Thrombosis - blood; Intracranial Thrombosis - genetics; Intracranial Thrombosis - immunology; Ischemia; Ischemic stroke; Male; Mechanical Thrombolysis - methods; Medical imaging; Microscopy; Middle Aged; Molecular biology; Mortality; Neutrophils; Neutrophils - immunology; Neutrophils - metabolism; Prospective Studies; RNA polymerase; SARS-CoV-2 - genetics; SARS-CoV-2 - immunology; SARS-CoV-2 - metabolism; SARS-CoV2; Severe acute respiratory syndrome coronavirus 2; Stroke; Stroke (Disease); Stroke - blood; Stroke - genetics; Stroke - immunology; Stroke patients; Thrombosis; Von Willebrand factor; X-rays
• ISSN: 2051-5960; 2051-5960
• DOI: 10.1186/s40478-022-01313-y

Coronavirus disease 2019 (COVID-19) is associated with an increased risk of thrombotic events. Ischemic stroke in COVID-19 patients entails high severity and mortality rates. Here we aimed to analyze cerebral thrombi of COVID-19 patients with large vessel occlusion (LVO) acute ischemic stroke to expose molecular evidence for SARS-CoV-2 in the thrombus and to unravel any peculiar immune-thrombotic features. We conducted a systematic pathological analysis of cerebral thrombi retrieved by endovascular thrombectomy in patients with LVO stroke infected with COVID-19 (n = 7 patients) and non-covid LVO controls (n = 23). In thrombi of COVID-19 patients, the SARS-CoV-2 docking receptor ACE2 was mainly expressed in monocytes/macrophages and showed higher expression levels compared to controls. Using polymerase chain reaction and sequencing, we detected SARS-CoV-2 Clade20A, in the thrombus of one COVID-19 patient. Comparing thrombus composition of COVID-19 and control patients, we noted no overt differences in terms of red blood cells, fibrin, neutrophil extracellular traps (NETs), von Willebrand Factor (vWF), platelets and complement complex C5b-9. However, thrombi of COVID-19 patients showed increased neutrophil density (MPO cells) and a three-fold higher Neutrophil-to-Lymphocyte Ratio (tNLR). In the ROC analysis both neutrophils and tNLR had a good discriminative ability to differentiate thrombi of COVID-19 patients from controls. In summary, cerebral thrombi of COVID-19 patients can harbor SARS-CoV2 and are characterized by an increased neutrophil number and tNLR and higher ACE2 expression. These findings suggest neutrophils as the possible culprit in COVID-19-related thrombosis.