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

      research-article
      a1 , a2 , a3 , a4 , a1 , a5 , a6 , a7 , a1 , a8 , a1 , a9 , a1 , a10 , a2 , a11 , a1 , a10 , a9 , a9 , a8 , a8 , a8 , a8 , a9 , a9 , a1 , a9 , a9 , a9 , a9 , a9 , a1 , a12 , a1 , a12 , a1 , a10 , a9 , a13 , a14 , a14 , a14 , a15 , a16 , a11 , a11 , a1 , a6 , a6 , a6 , a9 , a9 , a9 , a9 , a9 , a1 , a1 , a9 , a17 , a9 , a17 , a1 , a18 , a6 , a9 , a1 , a1 , a9 , a1 , a9 , the UCL Queen Square National Hospital for Neurology and Neurosurgery COVID-19 Study Group
      Brain
      Oxford University Press
      COVID-19, SARS-CoV-2, encephalitis, ADEM

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          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.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical Characteristics of Coronavirus Disease 2019 in China

            Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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              Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study

              Summary Background In December, 2019, a pneumonia associated with the 2019 novel coronavirus (2019-nCoV) emerged in Wuhan, China. We aimed to further clarify the epidemiological and clinical characteristics of 2019-nCoV pneumonia. Methods In this retrospective, single-centre study, we included all confirmed cases of 2019-nCoV in Wuhan Jinyintan Hospital from Jan 1 to Jan 20, 2020. Cases were confirmed by real-time RT-PCR and were analysed for epidemiological, demographic, clinical, and radiological features and laboratory data. Outcomes were followed up until Jan 25, 2020. Findings Of the 99 patients with 2019-nCoV pneumonia, 49 (49%) had a history of exposure to the Huanan seafood market. The average age of the patients was 55·5 years (SD 13·1), including 67 men and 32 women. 2019-nCoV was detected in all patients by real-time RT-PCR. 50 (51%) patients had chronic diseases. Patients had clinical manifestations of fever (82 [83%] patients), cough (81 [82%] patients), shortness of breath (31 [31%] patients), muscle ache (11 [11%] patients), confusion (nine [9%] patients), headache (eight [8%] patients), sore throat (five [5%] patients), rhinorrhoea (four [4%] patients), chest pain (two [2%] patients), diarrhoea (two [2%] patients), and nausea and vomiting (one [1%] patient). According to imaging examination, 74 (75%) patients showed bilateral pneumonia, 14 (14%) patients showed multiple mottling and ground-glass opacity, and one (1%) patient had pneumothorax. 17 (17%) patients developed acute respiratory distress syndrome and, among them, 11 (11%) patients worsened in a short period of time and died of multiple organ failure. Interpretation The 2019-nCoV infection was of clustering onset, is more likely to affect older males with comorbidities, and can result in severe and even fatal respiratory diseases such as acute respiratory distress syndrome. In general, characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia. Further investigation is needed to explore the applicability of the MuLBSTA score in predicting the risk of mortality in 2019-nCoV infection. Funding National Key R&D Program of China.
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                Author and article information

                Journal
                Brain
                Brain
                brainj
                Brain
                Oxford University Press
                0006-8950
                1460-2156
                08 July 2020
                : awaa240
                Affiliations
                [a1 ]University College London, Queen Square Institute of Neurology , London, UK
                [a2 ] Darent Valley Hospital , Dartford, Kent, UK
                [a3 ] UK Dementia Research Institute , London, UK
                [a4 ] UK Dementia Research Institute
                [a5 ] UCL Institute of Immunity and Transplantation , London, UK
                [a6 ] UCL Institute of Neurology , Stroke Research Centre, Russell Square House, London, UK
                [a7 ] University of Liverpool, Brain Infections Group , Liverpool, Merseyside, UK
                [a8 ] Wexham Park Hospital , Berkshire, UK
                [a9 ]National Hospital for Neurology and Neurosurgery, University College London Hospitals NHS Foundation Trust , Queen Square, London, UK
                [a10 ] Watford General Hospital , Watford, Hertfordshire, UK
                [a11 ] King’s College Hospital , Denmark Hill, London, UK
                [a12 ] Northwick Park Hospital , Harrow, London, UK
                [a13 ] Lister Hospital , Stevenage, Hertfordshire, UK
                [a14 ] Imperial College London , London, UK
                [a15 ] Barts and The London NHS Trust , London, UK
                [a16 ] UCL , Department of Physiology, London, UK
                [a17 ] Guy’s and Saint Thomas' Hospitals NHS Trust , London, UK
                [a18 ] University of Oxford, Nuffield Department of Clinical Neurosciences , John Radcliffe Hospital, Oxford, UK
                Author notes

                Ross W. Paterson, Rachel L. Brown, Hadi Manji, Michael S. Zandi. Contributed equally to this work.

                Correspondence to: Dr Michael S. Zandi PhD FRCP, University College London Queen Square Institute of Neurology, London, WC1N 3BG, UK. E-mail: m.zandi@ 123456ucl.ac.uk
                Article
                awaa240
                10.1093/brain/awaa240
                7454352
                32637987
                3011ecdd-0810-4c1b-8f3c-5bd1bec68210
                © 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.

                History
                : 01 June 2020
                : 29 June 2020
                : 30 June 2020
                Page count
                Pages: 36
                Categories
                Original Article
                Custom metadata
                accepted-manuscript
                PAP

                Neurosciences
                covid-19,sars-cov-2,encephalitis,adem
                Neurosciences
                covid-19, sars-cov-2, encephalitis, adem

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