key: cord-0801612-2fqr4792
authors: Stancu, Patrick; Uginet, Marjolaine; Assal, Frederic; Allali, Gilles; Lovblad, Karl-Olof
title: COVID-19 associated stroke and cerebral endotheliitis
date: 2021-02-04
journal: J Neuroradiol
DOI: 10.1016/j.neurad.2021.01.012
sha: a743c143d71f8a7572e0fc46fff3eb73d0eba6a2
doc_id: 801612
cord_uid: 2fqr4792

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He was admitted November 11, 2020 to our institution for fever, dry cough and dyspnea.

Chest CT showed ground-glass opacifications with light pleural effusion. The diagnosis of SARS-CoV-2 was ultimately confirmed by reverse transcriptase-polymerase chain reaction Due to the distribution of the stroke and the absence of necks vessels stenosis, anticoagulation treatment was maintained, with a switch to low molecular weight heparin.

Blood work showed an inflammatory syndrome with an elevated C-reactive protein (100mg/L), fibrinogen (6.9g/l) and coagulation activation with lightly elevated D-dimer (716ng/ml). Platelets count was normal and antiphospholipid antibodies were negative.

Transthoracic echocardiography did not detect a cardiac source of embolism.

Because of a deteriorating respiratory status with higher amounts of oxygen needed, the patient was transferred to the intermediate care unit for an acute respiratory distress syndrome and the patient unfortunately died a few days later from a cardiac arrest. Autopsy was denied by the family.

Acute cerebrovascular disease is a frequent manifestation of systemic COVID-19 disease [3] [4] [5] [6] [7] [8] . Although the mechanism of injury remains hypothetical, evidence of a SARS-CoV-2 mediated endotheliopathy is emerging [8] . Our case supports the hypothesis of cerebral COVID-19-associated endotheliopathy leading to stroke. In our patient, neuroimaging findings show diffuse multi territorial and border zones ischemic lesions, despite the absence of vessels neck stenosis or evidence of decreased arterial pressure ( Figure A [5] . Another study showed vessel wall enhancement with a different pattern than in our case [11] . A mechanism of direct virus-or/and indirect immune-mediated endothelial injury is considered [5] . SARS-CoV-2 uses a spike protein, the angiotensin converting enzyme 2 (ACE2) receptor to infect the host. ACE2 receptors are expressed ubiquitously in organs and tissues, among which endothelial cells [6] . Hence, our findings are supportive of an inflammation of cerebral arteries consistent with endothelial J o u r n a l P r e -p r o o f dysfunction leading to stroke. Additionally, even if vasa vasorum enhancement cannot be formally excluded, the morphology observed in our case is quite different: it is circumferential and not nodular; also arteriosclerotic enhancement is not usually circumferential and our case has no stenosis on TOF MRA.

The association of ischemic lesions in the same vascular territory is suggestive of an inflammatory vascular wall pathology that may participate to the mechanisms of COVID-19 cerebrovascular disorders. Hanafi et al. described the case of a COVID-19 patient with diffuse periventricular ischemic lesions and postcontrast enhancement pattern consistent with small vessel involvement [4] . Hypoxic-ischemic injury and a pro-thrombotic state was not considered a likely causative etiology and because of a characteristic combined imaging pattern of ischemia, hemorrhage and punctuate contrast enhancement, a SARS-CoV-2 induced endotheliitis was retained.

In conclusion, this case with an endotheliopathy suggestive an endotheliitis with multiple stroke supports the hypothesis of an inflammatory pathophysiological mechanism of brain vessels associated with stroke in COVID-19 patients. Future neuroimaging studies should include a systematic evaluation of brain vessel wall imaging in COVID-19 patients with stroke.

The authors declare that they have no competing interest.

J o u r n a l P r e -p r o o f

Large-Vessel Stroke as a Presenting Feature of Covid-19 in the Young

COVID-19 is Associated with an Unusual Pattern of Brain Microbleeds in Critically Ill Patients

COVID-19-related encephalopathy responsive to high-dose glucocorticoids

Neurologic Complication with CNS Vasculitis-Like Pattern

Large and Small Cerebral Vessel Involvement in Severe COVID-19: Detailed Clinical Workup of a Case Series

Endothelial cell infection and endotheliitis in COVID-19

Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease

Cerebrovascular disease in patients with COVID-19: neuroimaging, histological and clinical description

Intracranial Vessel Wall MRI: Principles and Expert Consensus Recommendations of the American Society of Neuroradiology

Intracranial vasa vasorum: insights and implications for imaging

imaging of the patient: diffusion-weighted images show hyperintensities in both hemispheres (A, B). Contrast-enhanced vessel wall imaging

of the right MCA (E). the TOF MRA show no stenosis or occlusion