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Neutrophils predominate the immune signature of cerebral thrombi in COVID-19 stroke patients.
Genchi, Angela; Semerano, Aurora; Schwarz, Ghil; Dell'Acqua, Beatrice; Gullotta, Giorgia Serena; Sampaolo, Michela; Boeri, Enzo; Quattrini, Angelo; Sanvito, Francesca; Diamanti, Susanna; Bergamaschi, Andrea; Grassi, Stefano; Podini, Paola; Panni, Pietro; Michelozzi, Caterina; Simionato, Franco; Scomazzoni, Francesco; Remida, Paolo; Valvassori, Luca; Falini, Andrea; Ferrarese, Carlo; Michel, Patrik; Saliou, Guillaume; Hajdu, Steven; Beretta, Simone; Roveri, Luisa; Filippi, Massimo; Strambo, Davide; Martino, Gianvito; Bacigaluppi, Marco.
  • Genchi A; Neuroimmunology Unit, Institute of Experimental Neurology, San Raffaele Hospital, Via Olgettina 60, 20132, Milan, Italy.
  • Semerano A; Department of Neurology, San Raffaele Hospital, Milan, Italy.
  • Schwarz G; University Vita-Salute San Raffaele, Milan, Italy.
  • Dell'Acqua B; Neuroimmunology Unit, Institute of Experimental Neurology, San Raffaele Hospital, Via Olgettina 60, 20132, Milan, Italy.
  • Gullotta GS; Department of Neurology, San Raffaele Hospital, Milan, Italy.
  • Sampaolo M; Department of Neurology, San Raffaele Hospital, Milan, Italy.
  • Boeri E; Department of Neurology and Stroke Unit, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy.
  • Quattrini A; Neuroimmunology Unit, Institute of Experimental Neurology, San Raffaele Hospital, Via Olgettina 60, 20132, Milan, Italy.
  • Sanvito F; Department of Neurology, San Raffaele Hospital, Milan, Italy.
  • Diamanti S; University Vita-Salute San Raffaele, Milan, Italy.
  • Bergamaschi A; Neuroimmunology Unit, Institute of Experimental Neurology, San Raffaele Hospital, Via Olgettina 60, 20132, Milan, Italy.
  • Grassi S; University Vita-Salute San Raffaele, Milan, Italy.
  • Podini P; Department of Microbiology and Virology, San Raffaele Hospital, Milan, Italy.
  • Panni P; Department of Microbiology and Virology, San Raffaele Hospital, Milan, Italy.
  • Michelozzi C; Department of Neurology, San Raffaele Hospital, Milan, Italy.
  • Simionato F; Neuropathology Unit, San Raffaele Hospital, Milan, Italy.
  • Scomazzoni F; Department of Medicine and Surgery, San Gerardo Hospital and Milano-Bicocca University, Milan, Italy.
  • Remida P; Neuroimmunology Unit, Institute of Experimental Neurology, San Raffaele Hospital, Via Olgettina 60, 20132, Milan, Italy.
  • Valvassori L; Department of Pathology, San Raffaele Hospital, Milan, Italy.
  • Falini A; Neuropathology Unit, San Raffaele Hospital, Milan, Italy.
  • Ferrarese C; Department of Neuroradiology, San Raffaele Hospital, Milan, Italy.
  • Michel P; Department of Neuroradiology, San Raffaele Hospital, Milan, Italy.
  • Saliou G; Department of Neuroradiology, San Raffaele Hospital, Milan, Italy.
  • Hajdu S; Department of Neuroradiology, San Raffaele Hospital, Milan, Italy.
  • Beretta S; Department of Neuroradiology, San Gerardo Hospital, Monza, Italy.
  • Roveri L; Department of Neuroradiology, San Gerardo Hospital, Monza, Italy.
  • Filippi M; University Vita-Salute San Raffaele, Milan, Italy.
  • Strambo D; Department of Neuroradiology, San Raffaele Hospital, Milan, Italy.
  • Martino G; Department of Medicine and Surgery, San Gerardo Hospital and Milano-Bicocca University, Milan, Italy.
  • Bacigaluppi M; Stroke Center, Neurology Service, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Acta Neuropathol Commun ; 10(1): 14, 2022 02 01.
Article in English | MEDLINE | ID: covidwho-1690864
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Brain Ischemia / Stroke / Intracranial Thrombosis / COVID-19 / Immunity, Cellular / Neutrophils Type of study: Cohort study / Observational study / Prognostic study / Systematic review/Meta Analysis Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: Acta Neuropathol Commun Year: 2022 Document Type: Article Affiliation country: S40478-022-01313-y

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Brain Ischemia / Stroke / Intracranial Thrombosis / COVID-19 / Immunity, Cellular / Neutrophils Type of study: Cohort study / Observational study / Prognostic study / Systematic review/Meta Analysis Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: Acta Neuropathol Commun Year: 2022 Document Type: Article Affiliation country: S40478-022-01313-y