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      Randomized elimination and prolongation of ACE inhibitors and ARBs in coronavirus 2019 (REPLACE COVID) Trial Protocol

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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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            Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention

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              An interactive web-based dashboard to track COVID-19 in real time

              In December, 2019, a local outbreak of pneumonia of initially unknown cause was detected in Wuhan (Hubei, China), and was quickly determined to be caused by a novel coronavirus, 1 namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The outbreak has since spread to every province of mainland China as well as 27 other countries and regions, with more than 70 000 confirmed cases as of Feb 17, 2020. 2 In response to this ongoing public health emergency, we developed an online interactive dashboard, hosted by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University, Baltimore, MD, USA, to visualise and track reported cases of coronavirus disease 2019 (COVID-19) in real time. The dashboard, first shared publicly on Jan 22, illustrates the location and number of confirmed COVID-19 cases, deaths, and recoveries for all affected countries. It was developed to provide researchers, public health authorities, and the general public with a user-friendly tool to track the outbreak as it unfolds. All data collected and displayed are made freely available, initially through Google Sheets and now through a GitHub repository, along with the feature layers of the dashboard, which are now included in the Esri Living Atlas. The dashboard reports cases at the province level in China; at the city level in the USA, Australia, and Canada; and at the country level otherwise. During Jan 22–31, all data collection and processing were done manually, and updates were typically done twice a day, morning and night (US Eastern Time). As the outbreak evolved, the manual reporting process became unsustainable; therefore, on Feb 1, we adopted a semi-automated living data stream strategy. Our primary data source is DXY, an online platform run by members of the Chinese medical community, which aggregates local media and government reports to provide cumulative totals of COVID-19 cases in near real time at the province level in China and at the country level otherwise. Every 15 min, the cumulative case counts are updated from DXY for all provinces in China and for other affected countries and regions. For countries and regions outside mainland China (including Hong Kong, Macau, and Taiwan), we found DXY cumulative case counts to frequently lag behind other sources; we therefore manually update these case numbers throughout the day when new cases are identified. To identify new cases, we monitor various Twitter feeds, online news services, and direct communication sent through the dashboard. Before manually updating the dashboard, we confirm the case numbers with regional and local health departments, including the respective centres for disease control and prevention (CDC) of China, Taiwan, and Europe, the Hong Kong Department of Health, the Macau Government, and WHO, as well as city-level and state-level health authorities. For city-level case reports in the USA, Australia, and Canada, which we began reporting on Feb 1, we rely on the US CDC, the government of Canada, the Australian Government Department of Health, and various state or territory health authorities. All manual updates (for countries and regions outside mainland China) are coordinated by a team at Johns Hopkins University. The case data reported on the dashboard aligns with the daily Chinese CDC 3 and WHO situation reports 2 for within and outside of mainland China, respectively (figure ). Furthermore, the dashboard is particularly effective at capturing the timing of the first reported case of COVID-19 in new countries or regions (appendix). With the exception of Australia, Hong Kong, and Italy, the CSSE at Johns Hopkins University has reported newly infected countries ahead of WHO, with Hong Kong and Italy reported within hours of the corresponding WHO situation report. Figure Comparison of COVID-19 case reporting from different sources Daily cumulative case numbers (starting Jan 22, 2020) reported by the Johns Hopkins University Center for Systems Science and Engineering (CSSE), WHO situation reports, and the Chinese Center for Disease Control and Prevention (Chinese CDC) for within (A) and outside (B) mainland China. Given the popularity and impact of the dashboard to date, we plan to continue hosting and managing the tool throughout the entirety of the COVID-19 outbreak and to build out its capabilities to establish a standing tool to monitor and report on future outbreaks. We believe our efforts are crucial to help inform modelling efforts and control measures during the earliest stages of the outbreak.
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                Author and article information

                Contributors
                (View ORCID Profile)
                (View ORCID Profile)
                Journal
                The Journal of Clinical Hypertension
                J Clin Hypertens
                Wiley
                1524-6175
                1751-7176
                September 16 2020
                Affiliations
                [1 ]Renal‐Electrolyte and Hypertension Division Perelman School of Medicine University of Pennsylvania Philadelphia PA USA
                [2 ]Department of Biostatistics, Epidemiology, and Informatics Perelman School of Medicine University of Pennsylvania Philadelphia PA USA
                [3 ]Division of Cardiovascular Medicine Hospital of the University of Pennsylvania and Perelman School of MedicineUniversity of Pennsylvania Philadelphia PA USA
                [4 ]Division of Infectious Diseases University of Ottawa and The Ottawa Hospital Research Institute Ottawa ON Canada
                [5 ]Division of Cardiology University of Arizona Tucson AZ USA
                [6 ]Hypertension Unit Department of Pathology Hospital Español de Mendoza National University of CuyoIMBECU‐CONICET Mendoza Argentina
                [7 ]Department of Medicine Hospital Nacional Carlos Alberto Seguín EscobedoEsSalud Arequipa Perú
                [8 ]Department of Nephrology Hospital Nacional Alberto Sabogal SologurenEsSalud Lima Perú
                [9 ]Department of Clinical Sciences Danderyd University HospitalKarolinska Institutet Stockholm Sweden
                [10 ]Universidad de Guadalajara Guadalajara Mexico
                [11 ]Division of Nephrology Stanford University School of Medicine Stanford CA USA
                [12 ]Universidad Católica de Buenos Aires Buenos Aires Argentina
                [13 ]Division of Cardiology Department of Medicine Duke University School of Medicine Durham NC USA
                [14 ]Cardiology Division University of Miami Miller School of Medicine Miami FL USA
                [15 ]Department of Nephrology Hospital Nacional Edgardo Rebagliati MartinsEsSalud Lima Perú
                [16 ]Department of Surgery Hospital of the University of PennsylvaniaUniversity of Pennsylvania Philadelphia PA USA
                [17 ]Palliative and Advanced Illness Research (PAIR) Center and Pulmonary and Critical Care Division Department of Medicine Perelman School of Medicine University of Pennsylvania Philadelphia PA USA
                [18 ]Division of Cardiovascular Medicine University of Michigan Medical School Ann Arbor MI USA
                [19 ]Division of Nephrology Department of Medicine Duke University School of Medicine Durham NC USA
                Article
                10.1111/jch.14011
                bab8e9df-2df3-47ff-bf3f-7f6dcbf2a495
                © 2020

                http://onlinelibrary.wiley.com/termsAndConditions#vor

                http://doi.wiley.com/10.1002/tdm_license_1.1

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