tetano
Editor, Senior Moderator
Acta Neuropathol Commun
. 2022 Feb 1;10(1):14.
doi: 10.1186/s40478-022-01313-y.
Neutrophils predominate the immune signature of cerebral thrombi in COVID-19 stroke patients
Angela Genchi[SUP] 1 2 3 [/SUP], Aurora Semerano[SUP] 1 2 [/SUP], Ghil Schwarz[SUP] 2 4 [/SUP], Beatrice Dell'Acqua[SUP] 1 2 3 [/SUP], Giorgia Serena Gullotta[SUP] 1 3 [/SUP], Michela Sampaolo[SUP] 5 [/SUP], Enzo Boeri[SUP] 5 [/SUP], Angelo Quattrini[SUP] 2 [/SUP], Francesca Sanvito[SUP] 6 [/SUP], Susanna Diamanti[SUP] 7 [/SUP], Andrea Bergamaschi[SUP] 1 [/SUP], Stefano Grassi[SUP] 8 [/SUP], Paola Podini[SUP] 6 [/SUP], Pietro Panni[SUP] 9 [/SUP], Caterina Michelozzi[SUP] 9 [/SUP], Franco Simionato[SUP] 9 [/SUP], Francesco Scomazzoni[SUP] 9 [/SUP], Paolo Remida[SUP] 10 [/SUP], Luca Valvassori[SUP] 10 [/SUP], Andrea Falini[SUP] 3 9 [/SUP], Carlo Ferrarese[SUP] 7 [/SUP], Patrik Michel[SUP] 11 [/SUP], Guillaume Saliou[SUP] 12 [/SUP], Steven Hajdu[SUP] 12 [/SUP], Simone Beretta[SUP] 7 [/SUP], Luisa Roveri[SUP] 2 [/SUP], Massimo Filippi[SUP] #[/SUP][SUP] 2 3 [/SUP], Davide Strambo[SUP] #[/SUP][SUP] 11 [/SUP], Gianvito Martino[SUP] #[/SUP][SUP] 1 3 [/SUP], Marco Bacigaluppi[SUP] #[/SUP][SUP] 13 14 15 [/SUP]
Affiliations
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[SUP]+[/SUP] 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.
Keywords: COVID-19; Endovascular treatment; Ischemic stroke; Neutrophils; SARS-CoV2; Thrombosis.
. 2022 Feb 1;10(1):14.
doi: 10.1186/s40478-022-01313-y.
Neutrophils predominate the immune signature of cerebral thrombi in COVID-19 stroke patients
Angela Genchi[SUP] 1 2 3 [/SUP], Aurora Semerano[SUP] 1 2 [/SUP], Ghil Schwarz[SUP] 2 4 [/SUP], Beatrice Dell'Acqua[SUP] 1 2 3 [/SUP], Giorgia Serena Gullotta[SUP] 1 3 [/SUP], Michela Sampaolo[SUP] 5 [/SUP], Enzo Boeri[SUP] 5 [/SUP], Angelo Quattrini[SUP] 2 [/SUP], Francesca Sanvito[SUP] 6 [/SUP], Susanna Diamanti[SUP] 7 [/SUP], Andrea Bergamaschi[SUP] 1 [/SUP], Stefano Grassi[SUP] 8 [/SUP], Paola Podini[SUP] 6 [/SUP], Pietro Panni[SUP] 9 [/SUP], Caterina Michelozzi[SUP] 9 [/SUP], Franco Simionato[SUP] 9 [/SUP], Francesco Scomazzoni[SUP] 9 [/SUP], Paolo Remida[SUP] 10 [/SUP], Luca Valvassori[SUP] 10 [/SUP], Andrea Falini[SUP] 3 9 [/SUP], Carlo Ferrarese[SUP] 7 [/SUP], Patrik Michel[SUP] 11 [/SUP], Guillaume Saliou[SUP] 12 [/SUP], Steven Hajdu[SUP] 12 [/SUP], Simone Beretta[SUP] 7 [/SUP], Luisa Roveri[SUP] 2 [/SUP], Massimo Filippi[SUP] #[/SUP][SUP] 2 3 [/SUP], Davide Strambo[SUP] #[/SUP][SUP] 11 [/SUP], Gianvito Martino[SUP] #[/SUP][SUP] 1 3 [/SUP], Marco Bacigaluppi[SUP] #[/SUP][SUP] 13 14 15 [/SUP]
Affiliations
- PMID: 35105380
- DOI: 10.1186/s40478-022-01313-y
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[SUP]+[/SUP] 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.
Keywords: COVID-19; Endovascular treatment; Ischemic stroke; Neutrophils; SARS-CoV2; Thrombosis.