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      Severe acute respiratory syndrome coronavirus 2 infection reaches the human nervous system: How?

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          Abstract

          Without protective and/or therapeutic agents the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection known as coronavirus disease 2019 is quickly spreading worldwide. It has surprising transmissibility potential, since it could infect all ages, gender, and human sectors. It attacks respiratory, gastrointestinal, urinary, hepatic, and endovascular systems and can reach the peripheral nervous system (PNS) and central nervous system (CNS) through known and unknown mechanisms. The reports on the neurological manifestations and complications of the SARS‐CoV‐2 infection are increasing exponentially. Herein, we enumerate seven candidate routes, which the mature or immature SARS‐CoV‐2 components could use to reach the CNS and PNS, utilizing the within‐body cross talk between organs. The majority of SARS‐CoV‐2–infected patients suffer from some neurological manifestations (e.g., confusion, anosmia, and ageusia). It seems that although the mature virus did not reach the CNS or PNS of the majority of patients, its unassembled components and/or the accompanying immune‐mediated responses may be responsible for the observed neurological symptoms. The viral particles and/or its components have been specifically documented in endothelial cells of lung, kidney, skin, and CNS. This means that the blood–endothelial barrier may be considered as the main route for SARS‐CoV‐2 entry into the nervous system, with the barrier disruption being more logical than barrier permeability, as evidenced by postmortem analyses.

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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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              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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                Author and article information

                Contributors
                vuversky@usf.edu
                lradwan@kau.edu.sa
                Journal
                J Neurosci Res
                J Neurosci Res
                10.1002/(ISSN)1097-4547
                JNR
                Journal of Neuroscience Research
                John Wiley and Sons Inc. (Hoboken )
                0360-4012
                1097-4547
                20 November 2020
                : 10.1002/jnr.24752
                Affiliations
                [ 1 ] Biological Science Department Faculty of Science King Abdulaziz University Jeddah Saudi Arabia
                [ 2 ] Department of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine University of South Florida Tampa FL USA
                [ 3 ] Institute for Biological Instrumentation of the Russian Academy of Sciences Federal Research Center “Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences” Pushchino Russia
                [ 4 ] Department of Endemic Medicine and Hepatogastroenterology Kasr Alainy School of Medicine Cairo University Cairo Egypt
                [ 5 ] Interdisciplinary Biotechnology Unit Aligarh Muslim University Aligarh India
                Author notes
                [*] [* ] Correspondence

                Vladimir N. Uversky and Elrashdy M. Redwan, Biological Science Department, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah, 21589, Saudi Arabia.

                Email: vuversky@ 123456usf.edu (V. N. U.) and lradwan@ 123456kau.edu.sa (E. M. R.)

                Author information
                https://orcid.org/0000-0002-4037-5857
                https://orcid.org/0000-0001-8246-0075
                Article
                JNR24752
                10.1002/jnr.24752
                7753416
                33217763
                75714924-4d5e-4c92-af9f-32a2f43c6a31
                © 2020 Wiley Periodicals LLC

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                : 17 August 2020
                : 19 October 2020
                : 21 October 2020
                Page count
                Figures: 3, Tables: 1, Pages: 28, Words: 68816
                Categories
                Review
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                Custom metadata
                2.0
                corrected-proof
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.6 mode:remove_FC converted:22.12.2020

                Neurosciences
                blood–brain barrier,bloodcerebrospinal‐fluid‐barrier,blood–nerve barrier,blood–nervous system barrier,covid‐19,double membrane vesicles cargo route,lymphatic brain drainage route,macrophage/monocytes cargo route,neurotropic virus,nicotinic acetylcholine receptor,olfactory route,peripheral nerve or neuronal retrograde route,sars‐cov‐2

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