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      Disease-modifying therapies and SARS-CoV-2 vaccination in multiple sclerosis: an expert consensus

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          Abstract

          Coronavirus disease (COVID-19) appeared in December 2019 in the Chinese city of Wuhan and has quickly become a global pandemic. The disease is caused by the severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2), an RNA beta coronavirus phylogenetically similar to SARS coronavirus. To date, more than 132 million cases of COVID19 have been recorded in the world, of which over 2.8 million were fatal ( https://coronavirus.jhu.edu/map.html). A huge vaccination campaign has started around the world since the end of 2020. The availability of vaccines has raised some concerns among neurologists regarding the safety and efficacy of vaccination in patients with multiple sclerosis (MS) taking immunomodulatory or immunosuppressive therapies.

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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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            SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

            Summary The recent emergence of the novel, pathogenic SARS-coronavirus 2 (SARS-CoV-2) in China and its rapid national and international spread pose a global health emergency. Cell entry of coronaviruses depends on binding of the viral spike (S) proteins to cellular receptors and on S protein priming by host cell proteases. Unravelling which cellular factors are used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal therapeutic targets. Here, we demonstrate that SARS-CoV-2 uses the SARS-CoV receptor ACE2 for entry and the serine protease TMPRSS2 for S protein priming. A TMPRSS2 inhibitor approved for clinical use blocked entry and might constitute a treatment option. Finally, we show that the sera from convalescent SARS patients cross-neutralized SARS-2-S-driven entry. Our results reveal important commonalities between SARS-CoV-2 and SARS-CoV infection and identify a potential target for antiviral intervention.
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              Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

              A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1-3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1-3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.
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                Author and article information

                Contributors
                filippi.massimo@hsr.it
                Journal
                J Neurol
                J Neurol
                Journal of Neurology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0340-5354
                1432-1459
                12 April 2021
                12 April 2021
                : 1-8
                Affiliations
                [1 ]GRID grid.6530.0, ISNI 0000 0001 2300 0941, Department of Systems Medicine, , Tor Vergata University, ; Rome, Italy
                [2 ]GRID grid.419543.e, ISNI 0000 0004 1760 3561, Unit of Neurology, , IRCCS Neuromed, ; Pozzilli (IS), Italy
                [3 ]GRID grid.18887.3e, ISNI 0000000417581884, MS Center and Neurology Unit, , IRCCS San Raffaele Scientific Institute, ; Via Olgettina, 60, 20132 Milan, Italy
                [4 ]GRID grid.18887.3e, ISNI 0000000417581884, Neurorehabilitation Unit, , IRCCS San Raffaele Scientific Institute, ; Milan, Italy
                [5 ]GRID grid.18887.3e, ISNI 0000000417581884, Neurophysiology Service, , IRCCS San Raffaele Scientific Institute, ; Milan, Italy
                [6 ]GRID grid.18887.3e, ISNI 0000000417581884, Neuroimaging Research Unit, Division of Neuroscience, , IRCCS San Raffaele Scientific Institute, ; Milan, Italy
                [7 ]GRID grid.15496.3f, Vita-Salute San Raffaele University, ; Milan, Italy
                [8 ]GRID grid.416308.8, ISNI 0000 0004 1805 3485, Department of Neurosciences, , San Camillo Forlanini Hospital, ; Rome, Italy
                [9 ]GRID grid.6612.3, ISNI 0000 0004 1937 0642, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), , Departments of Medicine, Clinical Research and Biomedicine and Biomedical Engineering, University Hospital and University of Basel, ; Basel, Switzerland
                [10 ]Department of Neurology, Medical Faculty, Heinrich-Heine University, University Hospital Duesseldorf, Düsseldorf, Germany
                [11 ]GRID grid.1013.3, ISNI 0000 0004 1936 834X, Brain and Mind Centre, , University of Sydney, ; Sydney, Australia
                [12 ]GRID grid.22937.3d, ISNI 0000 0000 9259 8492, Department of Neurology, , Medical University of Vienna, ; Wien, Austria
                [13 ]GRID grid.475435.4, Danish Multiple Sclerosis Center, Department of Neurology, , Copenhagen University Hospital, Rigshospitalet, ; Copenhagen, Denmark
                [14 ]GRID grid.411068.a, ISNI 0000 0001 0671 5785, Department of Neurology, , Hospital Clínico San Carlos, IdISSC, ; Madrid, Spain
                [15 ]GRID grid.4795.f, ISNI 0000 0001 2157 7667, Departamento de Medicina, Facultad de Medicina, , Universidad Complutense de Madrid (UCM), ; Madrid, Spain
                [16 ]GRID grid.7644.1, ISNI 0000 0001 0120 3326, Neurology and Neurophysiopathology Unit, Department of Basic Medical Sciences, Neuroscience and Sense Organs, , University of Bari “Aldo Moro”, ; Bari, Italy
                [17 ]GRID grid.16149.3b, ISNI 0000 0004 0551 4246, Department of Neurology, , University Hospital Münster, ; Münster, Germany
                Author information
                http://orcid.org/0000-0002-5485-0479
                Article
                10545
                10.1007/s00415-021-10545-2
                8038920
                33844056
                5b78ad79-acbf-4784-a58f-b50e2c243972
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 17 February 2021
                : 1 April 2021
                : 3 April 2021
                Categories
                Original Communication

                Neurology
                multiple sclerosis,disease-modifying treatments,vaccine,covid-19 pandemic
                Neurology
                multiple sclerosis, disease-modifying treatments, vaccine, covid-19 pandemic

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