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      A first case of meningitis/encephalitis associated with SARS-Coronavirus-2

      case-report
      a , * , b , a , a , a , a , a , a , a , a , c , d , e , f , g , h , i , g , j , k , k , l , l , l , m , n , k , k , o
      International Journal of Infectious Diseases
      The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
      SARS-CoV-2, COVID-19, Meningitis, Infections, Polymerase chain reaction

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          Highlights

          • Novel coronavirus (SARS-Coronavirus-2:SARS-CoV-2) which emerged in Wuhan, China, has spread to multiple countries rapidly.

          • This is the first case of meningitis associated with SARS-CoV-2 who was brought in by ambulance.

          • The specific SARS-CoV-2 RNA was not detected in the nasopharyngeal swab but was detected in a CSF.

          • This case warns the physicians of patients who have CNS symptoms.

          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 (day 2 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.

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          Most cited references8

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          Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China

          In December 2019, novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited.
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            Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding

            Summary Background In late December, 2019, patients presenting with viral pneumonia due to an unidentified microbial agent were reported in Wuhan, China. A novel coronavirus was subsequently identified as the causative pathogen, provisionally named 2019 novel coronavirus (2019-nCoV). As of Jan 26, 2020, more than 2000 cases of 2019-nCoV infection have been confirmed, most of which involved people living in or visiting Wuhan, and human-to-human transmission has been confirmed. Methods We did next-generation sequencing of samples from bronchoalveolar lavage fluid and cultured isolates from nine inpatients, eight of whom had visited the Huanan seafood market in Wuhan. Complete and partial 2019-nCoV genome sequences were obtained from these individuals. Viral contigs were connected using Sanger sequencing to obtain the full-length genomes, with the terminal regions determined by rapid amplification of cDNA ends. Phylogenetic analysis of these 2019-nCoV genomes and those of other coronaviruses was used to determine the evolutionary history of the virus and help infer its likely origin. Homology modelling was done to explore the likely receptor-binding properties of the virus. Findings The ten genome sequences of 2019-nCoV obtained from the nine patients were extremely similar, exhibiting more than 99·98% sequence identity. Notably, 2019-nCoV was closely related (with 88% identity) to two bat-derived severe acute respiratory syndrome (SARS)-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21, collected in 2018 in Zhoushan, eastern China, but were more distant from SARS-CoV (about 79%) and MERS-CoV (about 50%). Phylogenetic analysis revealed that 2019-nCoV fell within the subgenus Sarbecovirus of the genus Betacoronavirus, with a relatively long branch length to its closest relatives bat-SL-CoVZC45 and bat-SL-CoVZXC21, and was genetically distinct from SARS-CoV. Notably, homology modelling revealed that 2019-nCoV had a similar receptor-binding domain structure to that of SARS-CoV, despite amino acid variation at some key residues. Interpretation 2019-nCoV is sufficiently divergent from SARS-CoV to be considered a new human-infecting betacoronavirus. Although our phylogenetic analysis suggests that bats might be the original host of this virus, an animal sold at the seafood market in Wuhan might represent an intermediate host facilitating the emergence of the virus in humans. Importantly, structural analysis suggests that 2019-nCoV might be able to bind to the angiotensin-converting enzyme 2 receptor in humans. The future evolution, adaptation, and spread of this virus warrant urgent investigation. Funding National Key Research and Development Program of China, National Major Project for Control and Prevention of Infectious Disease in China, Chinese Academy of Sciences, Shandong First Medical University.
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              Identification of a Novel Coronavirus in Patients with Severe Acute Respiratory Syndrome

              The severe acute respiratory syndrome (SARS) has recently been identified as a new clinical entity. SARS is thought to be caused by an unknown infectious agent. Clinical specimens from patients with SARS were searched for unknown viruses with the use of cell cultures and molecular techniques. A novel coronavirus was identified in patients with SARS. The virus was isolated in cell culture, and a sequence 300 nucleotides in length was obtained by a polymerase-chain-reaction (PCR)-based random-amplification procedure. Genetic characterization indicated that the virus is only distantly related to known coronaviruses (identical in 50 to 60 percent of the nucleotide sequence). On the basis of the obtained sequence, conventional and real-time PCR assays for specific and sensitive detection of the novel virus were established. Virus was detected in a variety of clinical specimens from patients with SARS but not in controls. High concentrations of viral RNA of up to 100 million molecules per milliliter were found in sputum. Viral RNA was also detected at extremely low concentrations in plasma during the acute phase and in feces during the late convalescent phase. Infected patients showed seroconversion on the Vero cells in which the virus was isolated. The novel coronavirus might have a role in causing SARS. Copyright 2003 Massachusetts Medical Society
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                Author and article information

                Contributors
                Journal
                Int J Infect Dis
                Int. J. Infect. Dis
                International Journal of Infectious Diseases
                The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.
                1201-9712
                1878-3511
                3 April 2020
                May 2020
                3 April 2020
                : 94
                : 55-58
                Affiliations
                [a ]Department of Emergency and Critical Care Medicine, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi, 409-3898 Japan
                [b ]Department of Community and Family Medicine, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi, 409-3898 Japan
                [c ]Dean, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi, 409-3898 Japan
                [d ]Department of Urology, University of Yamanashi, Graduate School of Medical Sciences, 1110, Shimokato, Chuo, Yamanashi, 409-3898 Japan
                [e ]Department of Orthopaedic Surgery, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi, 409-3898 Japan
                [f ]Division of Infection Control and Prevention, University of Yamanashi Hospital, 1110, Shimokato, Chuo, Yamanashi, 409-3898 Japan
                [g ]Department of Clinical and Laboratory Medicine, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi, 409-3898 Japan
                [h ]Department of Nursing, University of Yamanashi Hospital, 1110, Shimokato, Chuo, Yamanashi, 409-3898 Japan
                [i ]Central Laboratory Unit/Division of Infection Control and Prevention, University of Yamanashi Hospital, 1110, Shimokato, Chuo, Yamanashi, 409-3898 Japan
                [j ]Department of Neurosurgery, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi, 409-3898 Japan
                [k ]Department of Clinical Quality and Medical Safety Management, University of Yamanashi Hospital, 1110, Shimokato, Chuo, Yamanashi, 409-3898 Japan
                [l ]Department of Radiology, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi, 409-3898 Japan
                [m ]First Department of Internal Medicine, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi, 409-3898 Japan
                [n ]Second Department of Internal medicine, University of Yamanashi, Faculty of Medicine, 1110, Shimokato, Chuo, Yamanashi, 409-3898 Japan
                [o ]President, University of Yamanashi, 1110, Shimokato, Chuo, Yamanashi, 409-3898 Japan
                Author notes
                [* ]Corresponding author. tmoriguchi@ 123456yamanashi.ac.jp
                Article
                S1201-9712(20)30195-8
                10.1016/j.ijid.2020.03.062
                7195378
                32251791
                600f179d-601c-4905-9473-513bbe08e5ab
                © 2020 The Author(s)

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                : 18 March 2020
                : 25 March 2020
                Categories
                Article

                Infectious disease & Microbiology
                sars-cov-2,covid-19,meningitis,infections,polymerase chain reaction

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