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      Potenciales mecanismos de neuroinvasión del SARS-CoV-2: una revisión de la literatura actual. Translated title: Potential neuroinvasion pathways of SARS-CoV-2: a review of the current literature.

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          Abstract

          RESUMEN Desde su inicio, en diciembre del 2019, la pandemia causada por el nuevo coronavirus 2019 (COVID-19), ha infectado a más de 116 millones de personas. A las bien documentadas manifestaciones respiratorias causadas por el SARS-CoV-2, se está añadiendo un creciente número de manifestaciones neurológicas y psiquiátricas entre los pacientes afectados y sobrevivientes. En este artículo se revisan y describen los potenciales mecanismos de invasión del virus al sistema nervioso. Sobre la base de estudios precedentes en coronavirus similares (MERS-CoV y SARS-CoV) y la evidencia actual, se plantea que las posibles rutas de neuroinvasión que emplea el SARS-CoV-2 son la transneuronal (vía axonal retrógrada, a través de los nervios periféricos), la hematógena/linfática (libre a través de la sangre y linfa o en el interior de las células inmunes) y la digestiva (mediante disrupción de la barrera intestinal). Si bien es necesario conducir más investigaciones en varias áreas, dilucidar las rutas de neuroinvasión, así como las capacidades neurotrópicas del virus, son puntos de vital importancia para entender y tratar las múltiples manifestaciones neurológicas y psiquiátricas, así como las potenciales secuelas a largo plazo que los pacientes infectados puedan desarrollar.

          Translated abstract

          SUMMARY Since its beginning, in December 2019, the pandemic caused by the coronavirus disease 2019 (COVID-19) has infected more than 116 millions of people. In addition to the well-documented respiratory manifestations caused by SARS-CoV-2, an increasing number of neurological and psychiatric manifestations are being reported among affected individuals and survivors. In this article we describe the potential invasion mechanisms of SARS-CoV-2 to the nervous system. On the basis of preceding studies on similar coronaviruses (MERS-CoV and SARS-CoV) and current evidence, three possible neuroinvasion routes used by SARS-CoV-2 are suggested: the transneuronal pathway (retrograde axonal pathway through the peripheral nerves), the hematogenous / lymphatic pathway (free through the blood and lymph or inside immune cells), and the digestive pathway (through disruption of the intestinal barrier). Although more research is needed in several areas, the elucidation of neuroinvasion routes and of the neurotropic capacities of the virus, are vital to understand and treat the multiple neurological and psychiatric manifestations as well as the long-term sequelae that the infected patients may potentially develop.

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          Most cited references49

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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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              Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China

              The outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, is serious and has the potential to become an epidemic worldwide. Several studies have described typical clinical manifestations including fever, cough, diarrhea, and fatigue. However, to our knowledge, it has not been reported that patients with COVID-19 had any neurologic manifestations.
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                Author and article information

                Journal
                rnp
                Revista de Neuro-Psiquiatría
                Rev Neuropsiquiatr
                Universidad Peruana Cayetano Heredia. Facultad de Medicina (Lima, , Peru )
                0034-8597
                January 2021
                : 84
                : 1
                : 25-32
                Affiliations
                [1] Lima Lima orgnameUniversidad de Piura orgdiv1Facultad de Medicina Humana Peru
                [2] Lima orgnameUniversidad de San Martín de Porres orgdiv1Facultad de Medicina orgdiv2Centro de Investigación en Salud Pública Peru
                [3] Lima orgnameEsSalud orgdiv1Hospital Nacional Guillermo Almenara Irigoyen orgdiv2Departamento de Psiquiatría Perú
                Article
                S0034-85972021000100025 S0034-8597(21)08400100025
                10.20453/rnp.v84i1.3935
                1817606a-6f6e-4629-a2ca-b0e0c3cb455d

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 16 March 2021
                : 05 December 2020
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 49, Pages: 8
                Product

                SciELO Peru

                Categories
                Artículos de revisión

                SARS-CoV-2,coronavirus,COVID-19,neuropsychiatry,pathophysiology,nervous system,neuropsiquiatría,fisiopatología,sistema nervioso

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