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. Graphical Abstract: [Figure not available: see fulltext.]

Genchi, A., Semerano, A., Schwarz, G., Dell'Acqua, B., Gullotta, G., Sampaolo, M., et al. (2022). Neutrophils predominate the immune signature of cerebral thrombi in COVID-19 stroke patients. ACTA NEUROPATHOLOGICA COMMUNICATIONS, 10(1 (December 2022)) [10.1186/s40478-022-01313-y].

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

Diamanti S.;Ferrarese C.;
2022

Abstract

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. Graphical Abstract: [Figure not available: see fulltext.]
Articolo in rivista - Articolo scientifico
COVID-19; Endovascular treatment; Ischemic stroke; Neutrophils; SARS-CoV2; Thrombosis;
English
Genchi, A., Semerano, A., Schwarz, G., Dell'Acqua, B., Gullotta, G., Sampaolo, M., et al. (2022). Neutrophils predominate the immune signature of cerebral thrombi in COVID-19 stroke patients. ACTA NEUROPATHOLOGICA COMMUNICATIONS, 10(1 (December 2022)) [10.1186/s40478-022-01313-y].
Genchi, A; Semerano, A; Schwarz, G; Dell'Acqua, B; Gullotta, G; Sampaolo, M; Boeri, E; Quattrini, A; Sanvito, F; Diamanti, S; Bergamaschi, A; Grassi, S; Podini, P; Panni, P; Michelozzi, C; Simionato, F; Scomazzoni, F; Remida, P; Valvassori, L; Falini, A; Ferrarese, C; Michel, P; Saliou, G; Hajdu, S; Beretta, S; Roveri, L; Filippi, M; Strambo, D; Martino, G; Bacigaluppi, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/362595
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