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.
Subject(s)
Brain Ischemia/immunology , COVID-19/immunology , Immunity, Cellular/physiology , Intracranial Thrombosis/immunology , Neutrophils/immunology , Stroke/immunology , 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 , COVID-19/blood , COVID-19/genetics , Female , Humans , Intracranial Thrombosis/blood , Intracranial Thrombosis/genetics , Male , Mechanical Thrombolysis/methods , Middle Aged , Neutrophils/metabolism , Prospective Studies , SARS-CoV-2/genetics , SARS-CoV-2/immunology , SARS-CoV-2/metabolism , Stroke/blood , Stroke/geneticsABSTRACT
Ten days after SARS-Cov2 reinfection with mild gastrointestinal symptoms and headache that occurred 2 months after an initial infection, a previously healthy 37-year-old woman developed fluctuating facial and upper limb paresthesia and weakness. Diffusion-weighted magnetic resonance imaging revealed ischemic lesions in the right parietal region of different stages within the same vascular territory. A cerebral angiography demonstrated an isolated focal arteriopathy with no other arterial involvement. Focal cerebral arteriopathy is exceedingly rare among adults and most commonly triggered by varicella-zoster virus reactivation. We present a case of focal cerebral arteriopathy in a patient with a recent reinfection with SARS-CoV-2.