#Encephalitic #syndrome and #anosmia in #COVID19: do these clinical presentations really reflect #SARS‐CoV‐2 #neurotropism? A theory based on the review of 25 COVID‐19 cases (J Med Virol., abstract)

[Source: Journal of Medical Virology, full page: (LINK). Abstract, edited.]

Encephalitic syndrome and anosmia in COVID‐19: do these clinical presentations really reflect SARS‐CoV‐2 neurotropism? A theory based on the review of 25 COVID‐19 cases

Lydia Pouga MD Virology PhD Neurosciences

First published: 16 July 2020 | DOI:  https://doi.org/10.1002/jmv.26309

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/jmv.26309

 

Abstract

Since the discovery of COVID‐19, a disease caused by the new coronavirus SARS‐CoV‐2, the pathology showed different faces. There is an increasing number of cases described as (meningo)encephalitis although evidence often lacks. Anosmia, another atypical form of COVID‐19, has been considered as testimony of the potential of neuroinvasiveness of SARS‐CoV‐2, though this hypothesis remains highly speculative. We did a review of the cases reported as brain injury caused by SARS‐CoV‐2. Over 98 papers found, 21 were analyzed. Only four publications provided evidence of the presence of SARS‐CoV‐2 within the CNS. When facing acute neurological abnormalities during an infectious episode it is often difficult to disentangle neurological symptoms induced by the brain infection and those due to the impact of host immune response on the CNS. Cytokines release can disturb neural cells functioning and can have in the most severe cases vascular and cytotoxic effects. An inappropriate immune response can lead to the production of auto‐antibodies directed toward CNS components. In the case of proven SARS‐CoV‐2 brain invasion, the main hypothesis found in the literature focus on a neural pathway, especially the direct route via the nasal cavity, although the virus is likely to reach the CNS using other routes. Our ability to come up with hypotheses about the mechanisms by which the virus might interact with the CNS may help to keep in mind that all neurological symptoms observed during COVID‐19 do not always rely on CNS viral invasion.

This article is protected by copyright. All rights reserved.

Keywords: SARS-CoV-2; COVID-19; Neuroinvasion; Encephalitis; Anosmia; Neurology.

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The emerging #spectrum of #COVID19 #neurology: #clinical, #radiological and #laboratory findings (Brain, abstract)

[Source: Brain, full page: (LINK). Abstract, edited.]

The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings

Ross W Paterson, Rachel L Brown, Laura Benjamin, Ross Nortley, Sarah Wiethoff, Tehmina Bharucha, Dipa L Jayaseelan, Guru Kumar, Rhian E Raftopoulos, Laura Zambreanu … et al.

Brain, awaa240, https://doi.org/10.1093/brain/awaa240

Published: 08 July 2020

 

Abstract

Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms, which will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.

COVID-19, SARS-CoV-2, encephalitis, ADEM

Issue Section: Original Article

This content is only available as a PDF.

© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords: SARS-CoV-2; COVID-19; Encephalitis; Encephalopathy; GBS; Stroke; Neurology.

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#Neurological and #neuropsychiatric #complications of #COVID19 in 153 patients: a #UK-wide surveillance study (Lancet Psychiatry, abstract)

[Source: Lancet Psychiatry, full page: (LINK). Abstract, edited.]

Neurological and neuropsychiatric complications of COVID-19 in 153 patients: a UK-wide surveillance study

Aravinthan Varatharaj, MRCP, Naomi Thomas, MRCPCH, Mark A Ellul, MRCP, Nicholas W S Davies, PhD, Thomas A Pollak, MRCP, Elizabeth L Tenorio, PhD, Mustafa Sultan, Ava Easton, PhD, Prof Gerome Breen, PhD, Michael Zandi, PhD, Prof Jonathan P Coles, PhD, Hadi Manji, FRCP, Prof Rustam Al-Shahi Salman, PhD, Prof David K Menon, PhD, Timothy R Nicholson, PhD, Laura A Benjamin, PhD, Prof Alan Carson, PhD, Prof Craig Smith, MD, Prof Martin R Turner, PhD, Prof Tom Solomon, PhD, Rachel Kneen, MRCPCH, Prof Sarah L Pett, PhD, Ian Galea, PhD *, Rhys H Thomas, PhD *, Benedict D Michael, PhD  *, on behalf of the CoroNerve Study Group †

Published: June 25, 2020 | DOI: https://doi.org/10.1016/S2215-0366(20)30287-X

 

Summary

Background

Concerns regarding potential neurological complications of COVID-19 are being increasingly reported, primarily in small series. Larger studies have been limited by both geography and specialty. Comprehensive characterisation of clinical syndromes is crucial to allow rational selection and evaluation of potential therapies. The aim of this study was to investigate the breadth of complications of COVID-19 across the UK that affected the brain.

Methods

During the exponential phase of the pandemic, we developed an online network of secure rapid-response case report notification portals across the spectrum of major UK neuroscience bodies, comprising the Association of British Neurologists (ABN), the British Association of Stroke Physicians (BASP), and the Royal College of Psychiatrists (RCPsych), and representing neurology, stroke, psychiatry, and intensive care. Broad clinical syndromes associated with COVID-19 were classified as a cerebrovascular event (defined as an acute ischaemic, haemorrhagic, or thrombotic vascular event involving the brain parenchyma or subarachnoid space), altered mental status (defined as an acute alteration in personality, behaviour, cognition, or consciousness), peripheral neurology (defined as involving nerve roots, peripheral nerves, neuromuscular junction, or muscle), or other (with free text boxes for those not meeting these syndromic presentations). Physicians were encouraged to report cases prospectively and we permitted recent cases to be notified retrospectively when assigned a confirmed date of admission or initial clinical assessment, allowing identification of cases that occurred before notification portals were available. Data collected were compared with the geographical, demographic, and temporal presentation of overall cases of COVID-19 as reported by UK Government public health bodies.

Findings

The ABN portal was launched on April 2, 2020, the BASP portal on April 3, 2020, and the RCPsych portal on April 21, 2020. Data lock for this report was on April 26, 2020. During this period, the platforms received notification of 153 unique cases that met the clinical case definitions by clinicians in the UK, with an exponential growth in reported cases that was similar to overall COVID-19 data from UK Government public health bodies. Median patient age was 71 years (range 23–94; IQR 58–79). Complete clinical datasets were available for 125 (82%) of 153 patients. 77 (62%) of 125 patients presented with a cerebrovascular event, of whom 57 (74%) had an ischaemic stroke, nine (12%) an intracerebral haemorrhage, and one (1%) CNS vasculitis. 39 (31%) of 125 patients presented with altered mental status, comprising nine (23%) patients with unspecified encephalopathy and seven (18%) patients with encephalitis. The remaining 23 (59%) patients with altered mental status fulfilled the clinical case definitions for psychiatric diagnoses as classified by the notifying psychiatrist or neuropsychiatrist, and 21 (92%) of these were new diagnoses. Ten (43%) of 23 patients with neuropsychiatric disorders had new-onset psychosis, six (26%) had a neurocognitive (dementia-like) syndrome, and four (17%) had an affective disorder. 18 (49%) of 37 patients with altered mental status were younger than 60 years and 19 (51%) were older than 60 years, whereas 13 (18%) of 74 patients with cerebrovascular events were younger than 60 years versus 61 (82%) patients older than 60 years.

Interpretation

To our knowledge, this is the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19. Altered mental status was the second most common presentation, comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients. This study provides valuable and timely data that are urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy.

Funding

None.

Keywords: SARS-CoV-2; COVID-19; Psychiatry; Neurology; Encephalitis; Encephalopathy.

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#COVID 19: a #global #threat to the #nervous system (Ann Neurol., abstract)

[Source: Annals of Neurology, full page: (LINK). Abstract, edited.]

COVID ‐19: a global threat to the nervous system

Igor. J Koralnik M.D.,  Kenneth L. Tyler M.D.

First published: 07 June 2020 | DOI:  https://doi.org/10.1002/ana.25807

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/ana.25807.

 

Abstract

In less than 6 months, the severe acute respiratory syndrome‐coronavirus type 2 (SARS‐CoV‐2) has spread worldwide infecting nearly 6 million people and killing over 350,000. Initially thought to be restricted to the respiratory system, we now understand that coronavirus disease 2019 (COVID‐19) also involves multiple other organs including the central and peripheral nervous system. The number of recognized neurologic manifestations of SARS‐CoV‐2 infection is rapidly accumulating. These may result from a variety of mechanisms including virus‐induced hyper‐inflammatory and hypercoagulable states, direct virus infection of the CNS, and post‐infectious immune mediated processes. Example of COVID‐19 CNS disease include encephalopathy, encephalitis, acute disseminated encephalomyelitis, meningitis, ischemic and hemorrhagic stroke, venous sinus thrombosis and endothelialitis. In the peripheral nervous system COVID‐19 is associated with dysfunction of smell and taste, muscle injury, the Guillain‐Barre syndrome and its variants. Due to its worldwide distribution and multifactorial pathogenic mechanisms, COVID‐19 poses a global threat to the entire nervous system. While our understanding of SARS‐CoV‐2 neuropathogenesis is still incomplete and our knowledge is evolving rapidly, we hope that this review will provide a useful framework and help neurologists in understanding the many neurologic facets of COVID‐19.

Keywords: SARS-CoV-2; COVID-19; Encephalopathy; Encephalitis; GBS; Neurology.

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#Encephalopathy and #Encephalitis Associated with #CSF #Cytokine #Alterations and #Coronavirus Disease, #Atlanta, #Georgia, #USA, 2020 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 26, Number 9—September 2020 | Synopsis

Encephalopathy and Encephalitis Associated with Cerebrospinal Fluid Cytokine Alterations and Coronavirus Disease, Atlanta, Georgia, USA, 2020

Karima Benameur1  , Ankita Agarwal1, Sara C. Auld, Matthew P. Butters, Andrew S. Webster, Tugba Ozturk, J. Christina Howell, Leda C. Bassit, Alvaro Velasquez, Raymond F. Schinazi, Mark E. Mullins, and William T. Hu

Author affiliations: Emory University School of Medicine, Atlanta, Georgia, USA

 

Abstract

There are few detailed investigations of neurologic complications in severe acute respiratory syndrome coronavirus 2 infection. We describe 3 patients with laboratory-confirmed coronavirus disease who development of encephalopathy and encephalitis. Neuroimaging showed nonenhancing unilateral, bilateral, and midline changes not readily attributable to vascular causes. All 3 patients had increased cerebrospinal fluid (CSF) levels of anti-S1 IgM. One patient who died also had increased levels of anti-envelope protein IgM. CSF analysis also showed markedly increased levels of interleukin (IL)-6, IL-8, and IL-10, but severe acute respiratory syndrome coronavirus 2 was not identified in any CSF sample. These changes provide evidence of CSF periinfectious/postinfectious inflammatory changes during coronavirus disease with neurologic complications.

Keywords: SARS-CoV-2; COVID-19; Cytokines; Encephalitis; Encephalopathy; USA; Georgia; Neurology.

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#Steroid‐responsive #encephalitis in #Covid19 disease (Ann Neurol., abstract)

[Source: Annals of Neurology, full page: (LINK). Abstract, edited.]

Steroid‐responsive encephalitis in Covid‐19 disease

Andrea Pilotto MD, Silvia Odolini MD,  S Stefano Masciocchi MD,  Agnese Comelli MD, Irene Volonghi MD,  Stefano Gazzina MD,  Sara Nocivelli Psy,  Alessandro Pezzini MD

First published: 17 May 2020 | DOI:  https://doi.org/10.1002/ana.25783

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/ana.25783.

 

Abstract

Covid‐19 infection has the potential for targeting the central nervous system and several neurological symptoms have been described in patients with severe respiratory distress. Here we described the case of a 60‐year old subject with SARS‐CoV‐2 infection but only mild respiratory abnormalities who developed an akinetic mutism due to encephalitis. MRI was negative whereas EEG showed generalized theta slowing. CSF analyses during the acute stage were negative for SARS‐CoV‐2, positive for pleocytosis and hyperproteinorrachia, and showed increased IL‐8 and TNF‐α concentrations while other infectious or autoimmune disorders were excluded. A progressive clinical improvement along with a reduction of CSF parameters was observed after high‐dose steroid treatment, thus arguing for an inflammatory‐mediated brain involvement related to Covid‐19.

This article is protected by copyright. All rights reserved.

Keywords: SARS-CoV-2; COVID-19; Encephalitis; Corticosteroids.

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The Use of Large-Particle #Aerosol #Exposure to #Nipah Virus to Mimic Human #Neurological Disease Manifestations in the African Green #Monkey (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

The Use of Large-Particle Aerosol Exposure to Nipah Virus to Mimic Human Neurological Disease Manifestations in the African Green Monkey

Ji Hyun Lee, Dima A Hammoud, Yu Cong, Louis M Huzella, Marcelo A Castro, Jeffrey Solomon, Joseph Laux, Matthew Lackemeyer, J Kyle Bohannon, Oscar Rojas, Russ Byrum, Ricky Adams, Danny Ragland, Marisa St Claire, Vincent Munster, Michael R Holbrook

The Journal of Infectious Diseases, Volume 221, Issue Supplement_4, 1 May 2020, Pages S419–S430, https://doi.org/10.1093/infdis/jiz502

Published: 05 November 2019

 

Abstract

Nipah virus (NiV) is an emerging virus associated with outbreaks of acute respiratory disease and encephalitis. To develop a neurological model for NiV infection, we exposed 6 adult African green monkeys to a large-particle (approximately 12 μm) aerosol containing NiV (Malaysian isolate). Brain magnetic resonance images were obtained at baseline, every 3 days after exposure for 2 weeks, and then weekly until week 8 after exposure. Four of six animals showed abnormalities reminiscent of human disease in brain magnetic resonance images. Abnormalities ranged from cytotoxic edema to vasogenic edema. The majority of lesions were small infarcts, and a few showed inflammatory or encephalitic changes. Resolution or decreased size in some lesions resembled findings reported in patients with NiV infection. Histological lesions in the brain included multifocal areas of encephalomalacia, corresponding to known ischemic foci. In other regions of the brain there was evidence of vasculitis, with perivascular infiltrates of inflammatory cells and rare intravascular fibrin thrombi. This animal model will help us better understand the acute neurological features of NiV infection and develop therapeutic approaches for managing disease caused by NiV infection.

Issue Section: supplement articles

Keywords: Nipah virus; Encephalitis; Animal models.

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#Neurological #Complications Associated With #Influenza in Season 2017/18 in #Austria- A Retrospective Single Center Study (J Clin Virol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Clin Virol. 2020 Mar 30;127:104340. doi: 10.1016/j.jcv.2020.104340. Online ahead of print.

Neurological Complications Associated With Influenza in Season 2017/18 in Austria- A Retrospective Single Center Study

Eirini Mylonaki 1, Andrea Harrer 2, Georg Pilz 2, Patrick Stalzer 3, Ferdinand Otto 2, Eugen Trinka 4, Peter Wipfler 2

Affiliations: 1 Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Ignaz-Harrer-Straße 79, 5020, Salzburg, Austria. Electronic address: e.mylonaki@salk.at. 2 Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Ignaz-Harrer-Straße 79, 5020, Salzburg, Austria. 3 Department of Infection Control and Hospital Epidemiology, Paracelsus Medical University, Müllner Hauptstraße 48, 5020, Salzburg, Austria. 4 Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Ignaz-Harrer-Straße 79, 5020, Salzburg, Austria; Centre of Neuroscience, Christian Doppler University Hospital Salzburg, Austria; Department of Public Health, Health Services Research and Health Technology Assessment, UMIT – University for Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria.

PMID: 32302952 DOI: 10.1016/j.jcv.2020.104340

 

Abstract

Background:

Neurological complications associated with influenza (NCI) are rare events in adults with seasonal influenza. Information about the characteristics of neurological complications and the burden of disease has been limited to case reports, mainly during the pandemic 2009. Influenza-associated encephalopathy/encephalitis (IAE) is one of the most severe and frequently reported NCI, mostly caused by influenza A. Isolated case reports exist about NCI caused by influenza B.

Objectives:

The aim of this single center retrospective study is the better understanding of the frequency and the characteristics of NCI in adults in season 2017-2018, depending on the influenza subtype A or B.

Study design:

We reviewed 874 adult patients with laboratory confirmed influenza admitted to the Christian Doppler University Hospital Salzburg, Austria from December 2017 until March 2018 looking for NCI.

Results:

37 (4 %) of the 874 patients with confirmed influenza had NCI. 4 (11 %) had influenza A and 33 (89 %) had influenza B. IAE was the most frequent complication diagnosed in 24 (65 %) patients, of whom all but one had influenza B and 3 (13 %) had neurological residuals. Moreover 6 (16 %) had isolated epileptic seizures, 2 (5 %) had acute inflammatory demyelinating polyneuropathy (AIDP), and 5 (14 %) were classified as having infection-associated stroke.

Conclusions:

We report an incidence of 4 % for NCI and a high frequency of IAE caused by subtype B. Therefore, we recommend considering both influenza A and B as an etiologic factor of encephalopathy and other neurological disease in adults.

Keywords: Influenza B; Influenza neurological complications; Influenza-associated encephalopathy.

Copyright © 2020 Elsevier B.V. All rights reserved.

Conflict of interest statement: Declaration of Competing Interest: Andrea Harrer, Georg Pilz and Patrick Stalzer authors declare that there is no conflict of interest. Eirini Mylonaki received funding for travel expenses and admission fees from Novartis. Ferdinand Otto received travel support from Novartis, Biogen, Merck Serono, Bayer, Teva, and Genzyme. Eugen Trinka reports personal fees from Eisai, personal fees from Everpharma, grants and personal fees from Biogen Idec, personal fees from Medtronics, personal fees from Bial, personal fees from Newbridge, grants and personal fees from UCB Pharma and Eisai, personal fees from GL Pharma, personal fees from GlaxoSmithKline, personal fees from Boehringer, personal fees from Viropharma, from Actavis, grants from Red Bull, grants from Merck, grants from European Union, grants from FWF Österreichischer Fond zur Wissenschaftsförderung, grants from Bundesministerium für Wissenschaft und Forschung, and grants from the Jubiläumsfond der Österreichischen Nationalbank, outside the submitted work. Peter Wipfler received a speaker’s honoraria/research funding/travel support from Novartis, Biogen, Merck Serono, Bayer, Teva, and Genzyme.

Keywords: Seasonal Influenza; Neurology; Encephalitis; Encephalopathy; Austria.

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A First Case of #Meningitis / #Encephalitis Associated With #SARS-Coronavirus-2 (Int J Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

 Int J Infect Dis 2020 Apr 3 [Online ahead of print]

A First Case of Meningitis/Encephalitis Associated With SARS-Coronavirus-2

Takeshi Moriguchi 1, Norikazu Harii 2, Junko Goto 3, Daiki Harada 3, Hisanori Sugawara 3, Junichi Takamino 3, Masateru Ueno 3, Hiroki Sakata 3, Kengo Kondo 3, Natsuhiko Myose 3, Atsuhito Nakao 4, Masayuki Takeda 5, Hirotaka Haro 6, Osamu Inoue 7, Katsue Suzuki-Inoue 8, Kayo Kubokawa 9, Shinji Ogihara 10, Tomoyuki Sasaki 8, Hiroyuki Kinouchi 11, Hiroyuki Kojin 12, Masami Ito 12, Hiroshi Onishi 13, Tatsuya Shimizu 13, Yu Sasaki 13, Nobuyuki Enomoto 14, Hiroshi Ishihara 15, Shiomi Furuya 12, Tomoko Yamamoto 12, Shinji Shimada 16

Affiliations: 1 Department of Emergency and Critical Care Medicine, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan. Electronic address: tmoriguchi@yamanashi.ac.jp. 2 Department of Community and Family Medicine, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan. 3 Department of Emergency and Critical Care Medicine, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan. 4 Dean, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi, 409-3898 Japan. 5 Department of Urology, University of Yamanashi, Graduate School of Medical Sciences, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan. 6 Department of Orthopaedic Surgery, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan. 7 Division of Infection Control and Prevention, University of Yamanashi Hospital, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan. 8 Department of Clinical and Laboratory Medicine, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan. 9 Department of Nursing, University of Yamanashi Hospital, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan. 10 Central Laboratory Unit / Division of Infection Control and Prevention, University of Yamanashi Hospital, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan. 11 Department of Neurosurgery, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan. 12 Department of Clinical Quality and Medical Safety Management, University of Yamanashi Hospital, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan. 13 Department of Radiology, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan. 14 First Department of Internal Medicine, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan. 15 Second Department of Internal medicine, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan. 16 President, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898, Japan.

PMID: 32251791 DOI: 10.1016/j.ijid.2020.03.062

 

Abstract

Novel coronavirus (SARS-Coronavirus-2:SARS-CoV-2) which emerged in Wuhan, China, has spread to multiple countries rapidly. We report the first case of meningitis associated with SARS-CoV-2 who was brought in by ambulance due to a convulsion accompanied by unconsciousness. He had never been to any foreign countries. He felt generalized fatigue and fever (day 1). He saw doctors nearby twice (day2 and 5) and was prescribed Laninamivir and antipyretic agents, His family visited his home and found that he was unconsciousness and lying on the floor in his vomit. He was immediately transported to this hospital by ambulance (day 9). Under emergency transport, he had transient generalized seizures that lasted about a minute. He had obvious neck stiffness. The specific SARS-CoV-2 RNA was not detected in the nasopharyngeal swab but was detected in a CSF. Anti- HSV 1 and varicella-zoster IgM antibodies were not detected in serum samples. A brain MRI showed hyperintensity along the wall of right lateral ventricle and hyperintense signal changes in the right mesial temporal lobe and hippocampus, suggesting the possibility of SARS-CoV-2 meningitis. This case warns the physicians of patients who have CNS symptoms.

Keywords: COVID-19; SARS-CoV-2; infections; meningitis; polymerase chain reaction.

Copyright © 2020. Published by Elsevier Ltd.

Keywords: SARS-CoV-2; COVID-19; Encephalitis; Meningitis; Neuroinvasion.

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#Zoonotic #spillover #infections with #Borna disease virus 1 leading to #fatal #human #encephalitis, 1999–2019: an epidemiological investigation (J Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Zoonotic spillover infections with Borna disease virus 1 leading to fatal human encephalitis, 1999–2019: an epidemiological investigation

Hans Helmut Niller, MD †, Klemens Angstwurm, MD †, Dennis Rubbenstroth, DVM †, Kore Schlottau, PhD, Arnt Ebinger, MSc, Sebastian Giese, PhD, Silke Wunderlich, MD, Prof Bernhard Banas, MD, Leonie F Forth, PhD, Donata Hoffmann, DVM, Dirk Höper, PhD, Prof Martin Schwemmle, PhD, Prof Dennis Tappe, MD, Prof Jonas Schmidt-Chanasit, MD, Daniel Nobach, DVM, Prof Christiane Herden, DVM, Prof Christoph Brochhausen, MD, Natalia Velez-Char, MD, Andreas Mamilos, MD, Kirsten Utpatel, MD, Prof Matthias Evert, MD, Saida Zoubaa, MD, Prof Markus J Riemenschneider, MD, Viktoria Ruf, MD, Prof Jochen Herms, MD, Georg Rieder, MD, Mario Errath, MD, Prof Kaspar Matiasek, DVM, Prof Jürgen Schlegel, MD, Friederike Liesche-Starnecker, MD, Bernhard Neumann, MD, Kornelius Fuchs, MD, Prof Ralf A Linker, MD, Prof Bernd Salzberger, MD, Tobias Freilinger, MD, Lisa Gartner, MD, Prof Jürgen J Wenzel, MD, Prof Udo Reischl, PhD, Prof Wolfgang Jilg, MD, Prof André Gessner, MD, Prof Jonathan Jantsch, MD, Prof Martin Beer, DVM  †, Prof Barbara Schmidt, MD †

Published: January 07, 2020 / DOI: https://doi.org/10.1016/S1473-3099(19)30546-8

 

Summary

Background

In 2018–19, Borna disease virus 1 (BoDV-1), the causative agent of Borna disease in horses, sheep, and other domestic mammals, was reported in five human patients with severe to fatal encephalitis in Germany. However, information on case frequencies, clinical courses, and detailed epidemiological analyses are still lacking. We report the occurrence of BoDV-1-associated encephalitis in cases submitted to the Institute of Clinical Microbiology and Hygiene, Regensburg University Hospital, Regensburg, Germany, and provide a detailed description of newly identified cases of BoDV-1-induced encephalitis.

Methods

All brain tissues from 56 encephalitis cases from Bavaria, Germany, of putative viral origin (1999–2019), which had been submitted for virological testing upon request of the attending clinician and stored for stepwise diagnostic procedure, were systematically screened for BoDV-1 RNA. Two additional BoDV-1-positive cases were contributed by other diagnostic centres. Positive results were confirmed by deep sequencing, antigen detection, and determination of BoDV-1-reactive antibodies in serum and cerebrospinal fluid. Clinical and epidemiological data from infected patients were collected and analysed.

Findings

BoDV-1 RNA and bornavirus-reactive antibodies were detected in eight newly analysed encephalitis cases and the first human BoDV-1 isolate was obtained from an unequivocally confirmed human BoDV-1 infection from the endemic area. Six of the eight BoDV-1-positive patients had no record of immunosuppression before the onset of fatal disease, whereas two were immunocompromised after solid organ transplantation. Typical initial symptoms were headache, fever, and confusion, followed by various neurological signs, deep coma, and severe brainstem involvement. Seven of nine patients with fatal encephalitis of unclear cause were BoDV-1 positive within one diagnostic centre. BoDV-1 sequence information and epidemiological analyses indicated independent spillover transmissions most likely from the local wild animal reservoir.

Interpretation

BoDV-1 infection has to be considered as a potentially lethal zoonosis in endemic regions with reported spillover infections in horses and sheep. BoDV-1 infection can result in fatal encephalitis in immunocompromised and apparently healthy people. Consequently, all severe encephalitis cases of unclear cause should be tested for bornaviruses especially in endemic regions.

Funding

German Federal Ministry of Education and Research.

Keywords: Borna Disease Virus 1; Encephalitis; Human; Germany.

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