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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 1 2 3 , Aurora Semerano 1 2 , Ghil Schwarz 2 4 , Beatrice Dell'Acqua 1 2 3 , Giorgia Serena Gullotta 1 3 , Michela Sampaolo 5 , Enzo Boeri 5 , Angelo Quattrini 2 , Francesca Sanvito 6 , Susanna Diamanti 7 , Andrea Bergamaschi 1 , Stefano Grassi 8 , Paola Podini 6 , Pietro Panni 9 , Caterina Michelozzi 9 , Franco Simionato 9 , Francesco Scomazzoni 9 , Paolo Remida 10 , Luca Valvassori 10 , Andrea Falini 3 9 , Carlo Ferrarese 7 , Patrik Michel 11 , Guillaume Saliou 12 , Steven Hajdu 12 , Simone Beretta 7 , Luisa Roveri 2 , Massimo Filippi # 2 3 , Davide Strambo # 11 , Gianvito Martino # 1 3 , Marco Bacigaluppi # 13 14 15
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+ 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.