key: cord-1020980-de97wi66 authors: Paniz‐Mondolfi, Alberto; Bryce, Clare; Grimes, Zachary; Gordon, Ronald E; Reidy, Jason; Lednicky, John; Sordillo, Emilia Mia; Fowkes, Mary title: Central Nervous System Involvement by Severe Acute Respiratory Syndrome Coronavirus ‐2 (SARS‐CoV‐2) date: 2020-04-21 journal: J Med Virol DOI: 10.1002/jmv.25915 sha: 4ae60ab3c27ec3cb8747f557872030adbd7b00b9 doc_id: 1020980 cord_uid: de97wi66 Neurologic sequelae can be devastating complications of respiratory viral infections. We report the presence of virus in neural and capillary endothelial cells in frontal lobe tissue obtained at postmortem examination from a patient infected with Severe Acute Respiratory Syndrome Coronavirus‐2 (SARS‐CoV‐2). Our observations of virus in neural tissue, in conjunction with clinical correlates of worsening neurologic symptoms, pave the way to a closer understanding of the pathogenic mechanisms underlying CNS involvement by SARS‐CoV‐2. This article is protected by copyright. All rights reserved. 38.9°C, thrombocytopenia (122,000/µL, reference range 150,000-450,000/µL), and SpO2 = 94% on room air. Chest radiography showed an enlarged cardiac silhouette and tortuous aorta, but no infiltrates. Findings on computerized tomography of the head were nonspecific with patchy subcortical and periventricular hypodensities unchanged from a scan 6 months earlier. Treatment with oral hydroxychloroquine and subcutaneous enoxaparin was initiated. Over the next 4 days he was intermittently alert and at times agitated and combative. He was persistently febrile, with episodes of hypotension and progressively worsening SpO2. On day 5, he developed new onset atrial fibrillation with a rapid ventricular rate and QTc prolongation to 515ms. His blood pressure improved after a bolus of intravenous fluid and initiation of amiodarone, with reversion to normal sinus rhythm. Hydroxychloroquine was discontinued, and intravenous tocilizumab and metoprolol were started. Repeat chest radiography showed new left basilar densities consistent with left lower lobe consolidation and a component of pleural fluid, right basilar densities, and patchy densities in the right midlung. He continued to decompensate clinically and expired on day 11. During the hospital course, the inflammatory markers C-reactive protein (CRP) and ferritin rose to peak on day 7 at 183.5 mg/L (CRP reference range 0.0-5.0 mg/L) and 2837 ng/mL (ferritin reference range 30-400 ng/mL), respectively, then declined to 10.7 mg/L and 1063 ng/mL by day 11. The D-dimer level rose from 0.74 µg/mL FEU (reference range 0.00-0.50 µg/mL FEU) on day 3, to 5.85 µg/mL FEU at day 10. The clinical spectrum of SARS-CoV-2 infection continues to broaden, raising crucial fundamental questions regarding its cellular tropism and pathogenic mechanisms. Our observations provide first evidence for the direct propagation and presence of SARS-CoV-2 in human brain tissue; hematogenous dissemination and brain capillary endothelial cells of the brain-blood-barrier in SARS-CoV-2-infected individuals are hypothesized to enable pathogen entry into the CNS, and consequent virus-induced neuropathic effects. In addition, our observations of virus in neural tissue, in conjunction with clinical correlates of worsening neurologic symptoms, pave the way to a closer understanding of the pathogenic mechanisms underlying CNS involvement. However, these results should be interpreted with caution. Further immunohistochemistry, in situ hybridization and ultrastructural studies including immuno-labeling will enable better assessment of SARS-CoV-2 distribution and help Accepted Article to elucidate the early events driving its potential neurovirulence and neuroinvasiveness. 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