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

Acta Neuropathologica Communications

Susanna Diamanti¹  Carlo Ferrarese¹  Simone Beretta¹  Enzo Boeri²  Michela Sampaolo²  Luisa Roveri³  Angelo Quattrini³  Ghil Schwarz⁴  Massimo Filippi⁵  Luca Valvassori⁶  Paolo Remida⁶  Caterina Michelozzi⁷  Francesco Scomazzoni⁷  Pietro Panni⁷  Franco Simionato⁷  Stefano Grassi⁸  Andrea Bergamaschi⁹  Aurora Semerano^1,10  Angela Genchi^1,11  Beatrice Dell’Acqua^1,11  Marco Bacigaluppi^1,11  Gianvito Martino^1,12  Giorgia Serena Gullotta^1,12  Paola Podini^1,13  Francesca Sanvito^1,13  Steven Hajdu^1,14  Guillaume Saliou^1,14  Davide Strambo^1,15  Patrik Michel^1,15  Andrea Falini^1,16 

[1] Department of Medicine and Surgery, San Gerardo Hospital and Milano–Bicocca University, Milan, Italy;Department of Microbiology and Virology, San Raffaele Hospital, Milan, Italy;Department of Neurology, San Raffaele Hospital, Milan, Italy;Department of Neurology, San Raffaele Hospital, Milan, Italy;Department of Neurology and Stroke Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy;Department of Neurology, San Raffaele Hospital, Milan, Italy;University Vita-Salute San Raffaele, Milan, Italy;Department of Neuroradiology, San Gerardo Hospital, Monza, Italy;Department of Neuroradiology, San Raffaele Hospital, Milan, Italy;Department of Pathology, San Raffaele Hospital, Milan, Italy;Neuroimmunology Unit, Institute of Experimental Neurology, San Raffaele Hospital, Via Olgettina 60, 20132, Milan, Italy;Neuroimmunology Unit, Institute of Experimental Neurology, San Raffaele Hospital, Via Olgettina 60, 20132, Milan, Italy;Department of Neurology, San Raffaele Hospital, Milan, Italy;Neuroimmunology Unit, Institute of Experimental Neurology, San Raffaele Hospital, Via Olgettina 60, 20132, Milan, Italy;Department of Neurology, San Raffaele Hospital, Milan, Italy;University Vita-Salute San Raffaele, Milan, Italy;Neuroimmunology Unit, Institute of Experimental Neurology, San Raffaele Hospital, Via Olgettina 60, 20132, Milan, Italy;University Vita-Salute San Raffaele, Milan, Italy;Neuropathology Unit, San Raffaele Hospital, Milan, Italy;Service of Diagnostic and Interventional Radiology, Interventional Neuroradiological Unit, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland;Stroke Center, Neurology Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland;University Vita-Salute San Raffaele, Milan, Italy;Department of Neuroradiology, San Raffaele Hospital, Milan, Italy;

关键词: SARS-CoV2;    COVID-19;    Thrombosis;    Neutrophils;    Ischemic stroke;    Endovascular treatment;   

DOI  :  10.1186/s40478-022-01313-y

来源: Springer

【 摘 要 】

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

【 授权许可】

CC BY