Neutrophils predominate the immune signature of cerebral thrombi in COVID-19 stroke patients.
Details
Serval ID
serval:BIB_C808421C9184
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Neutrophils predominate the immune signature of cerebral thrombi in COVID-19 stroke patients.
Journal
Acta neuropathologica communications
ISSN
2051-5960 (Electronic)
ISSN-L
2051-5960
Publication state
Published
Issued date
01/02/2022
Peer-reviewed
Oui
Volume
10
Number
1
Pages
14
Language
english
Notes
Publication types: Journal Article ; Multicenter Study
Publication Status: epublish
Publication Status: epublish
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
Aged, Aged, 80 and over, Angiotensin-Converting Enzyme 2/blood, Angiotensin-Converting Enzyme 2/genetics, Angiotensin-Converting Enzyme 2/immunology, Brain Ischemia/blood, Brain Ischemia/genetics, Brain Ischemia/immunology, COVID-19/blood, COVID-19/genetics, COVID-19/immunology, Female, Humans, Immunity, Cellular/physiology, Intracranial Thrombosis/blood, Intracranial Thrombosis/genetics, Intracranial Thrombosis/immunology, Male, Mechanical Thrombolysis/methods, Middle Aged, Neutrophils/immunology, Neutrophils/metabolism, Prospective Studies, SARS-CoV-2/genetics, SARS-CoV-2/immunology, SARS-CoV-2/metabolism, Stroke/blood, Stroke/genetics, Stroke/immunology, COVID-19, Endovascular treatment, Ischemic stroke, Neutrophils, SARS-CoV2, Thrombosis
Pubmed
Web of science
Open Access
Yes
Create date
08/02/2022 9:32
Last modification date
23/11/2022 8:15