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      ACE‐inhibitors and Angiotensin‐2 Receptor Blockers are not associated with severe SARS‐COVID19 infection in a multi‐site UK acute Hospital Trust

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          Abstract

          Aims

          The SARS‐Cov2 virus binds to the ACE2 receptor for cell entry. It has been suggested that ACE‐inhibitors (ACEi) and Angiotensin‐2 Blockers (ARB), which are commonly used in patients with hypertension or diabetes and may raise tissue ACE2 levels, could increase the risk of severe COVID19 infection.

          Methods and Results

          We evaluated this hypothesis in a consecutive cohort of 1200 acute inpatients with COVID19 at two hospitals with a multi‐ethnic catchment population in London (UK). The mean age was 68 ± 17 years (57% male) and 74% of patients had at least 1 comorbidity. 415 patients (34.6%) reached the primary endpoint of death or transfer to a critical care unit for organ support within 21‐days of symptom onset. 399 patients (33.3%) were taking ACEi or ARB. Patients on ACEi/ARB were significantly older and had more comorbidities. The odds ratio (OR) for the primary endpoint in patients on ACEi and ARB, after adjustment for age, sex and co‐morbidities, was 0.63 (CI 0.47–0.84, p < 0.01).

          Conclusions

          There was no evidence for increased severity of COVID19 disease in hospitalised patients on chronic treatment with ACEi or ARB. A trend towards a beneficial effect of ACEi/ARB requires further evaluation in larger meta‐analyses and randomised clinical trials.

          This article is protected by copyright. All rights reserved.

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          Most cited references25

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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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            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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              Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area

              There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19).
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                Author and article information

                Contributors
                daniel.bean@kcl.ac.uk
                ajay.shah@kcl.ac.uk
                jamesteo@nhs.net
                richard.j.dobson@kcl.ac.uk
                Journal
                Eur J Heart Fail
                Eur. J. Heart Fail
                10.1002/(ISSN)1879-0844
                EJHF
                European Journal of Heart Failure
                John Wiley & Sons, Ltd. (Oxford, UK )
                1388-9842
                1879-0844
                02 June 2020
                : 10.1002/ejhf.1924
                Affiliations
                [ 1 ] Department of Biostatistics and Health Informatics Institute of Psychiatry, Psychology and Neuroscience, King's College London London UK
                [ 2 ] Health Data Research UK London, University College London London UK
                [ 3 ] Institute of Health Informatics, University College London London UK
                [ 4 ] NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London London UK
                [ 5 ] King's College Hospital NHS Foundation Trust London UK
                [ 6 ] School of Cardiovascular Medicine & Sciences, King's College London British Heart Foundation Centre of Excellence London UK
                [ 7 ] NIHR Biomedical Research Centre at University College London Hospitals NHS Foundation Trust London UK
                [ 8 ] Dept of Clinical Neuroscience Institute of Psychiatry, Psychology and Neuroscience, King's College London London UK
                Author notes
                [*] [* ] Corresponding author

                Prof Richard Dobson, Dept of Biostatistics and Health Informatics, Institute of Psychiatry, Psychology and Neuroscience, King's College London, 6 De Crespigny Park, London SE5 8AF, UK Email: richard.j.dobson@ 123456kcl.ac.uk .

                Or: Dr Dan Bean Email: daniel.bean@ 123456kcl.ac.uk ; Dr James Teo Email: jamesteo@ 123456nhs.net ; Prof Ajay Shah

                Email: ajay.shah@ 123456kcl.ac.uk

                [†]

                joint author

                Article
                EJHF1924 na
                10.1002/ejhf.1924
                7301045
                32485082
                82ac41cd-5e5b-4ea4-a4f9-a427dc07515d
                This article is protected by copyright. All rights reserved.

                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
                : 09 May 2020
                : 22 May 2020
                : 27 May 2020
                Page count
                Figures: 2, Tables: 2, Pages: 1, Words: 600
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                accepted-manuscript
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.4 mode:remove_FC converted:18.06.2020

                Cardiovascular Medicine
                covid19,angiotensin converting enzyme inhibitors,hypertension,disease outcome

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