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

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State: Public
Version: Final published version
License: CC BY 4.0
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
Author(s)
Genchi A., Semerano A., Schwarz G., Dell'Acqua B., Gullotta G.S., 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.
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
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
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