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      Position Paper of the Department of Hypertension of the Brazilian Society of Nephrology: Use of renin-angiotensin system blockers during the course of Covid-19 infection Translated title: Posicionamento do Departamento de Hipertensão da Sociedade Brasileira de Nefrologia: Bloqueadores do sistema renina-angiotensina durante o curso de infecção pela Covid-19

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          ABSTRACT

          This position statement of the Department of Hypertension of the Brazilian Society of Nephrology (SBN) addresses the controversy surrounding the use or suspension/replacement of the renin-angiotensin-aldosterone system blockers (particularly inhibitors of the angiotensin-converting enzyme or angiotensin II AT1 receptor blockers) prophylactically in individuals using these drugs, due to the possibility of allegedly worsening the prognosis of hypertensive patients infected with SARS-CoV-2. The SBN Hypertension Department recommends individualizing treatment and maintaining these medications until better scientific evidence is available.

          RESUMO

          Este posicionamento do Departamento de Hipertensão da Sociedade Brasileira de Nefrologia (SBN) trata da polêmica gerada em torno do uso ou da suspensão/substituição dos bloqueadores do sistema renina-angiotensina-aldosterona (particularmente inibidores da enzima de conversão da angiotensina ou bloqueadores dos receptores AT 1da angiotensina II) profilaticamente em indivíduos que utilizam esses medicamentos, devido à possibilidade de supostamente piorar o prognóstico de pacientes hipertensos infectados pelo SARS-CoV-2. O Departamento de Hipertensão da SBN recomenda a individualização do tratamento e a manutenção dessas medicações até que melhores evidências científicas estejam disponíveis.

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          Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?

          The most distinctive comorbidities of 32 non-survivors from a group of 52 intensive care unit patients with novel coronavirus disease 2019 (COVID-19) in the study by Xiaobo Yang and colleagues 1 were cerebrovascular diseases (22%) and diabetes (22%). Another study 2 included 1099 patients with confirmed COVID-19, of whom 173 had severe disease with comorbidities of hypertension (23·7%), diabetes mellitus (16·2%), coronary heart diseases (5·8%), and cerebrovascular disease (2·3%). In a third study, 3 of 140 patients who were admitted to hospital with COVID-19, 30% had hypertension and 12% had diabetes. Notably, the most frequent comorbidities reported in these three studies of patients with COVID-19 are often treated with angiotensin-converting enzyme (ACE) inhibitors; however, treatment was not assessed in either study. Human pathogenic coronaviruses (severe acute respiratory syndrome coronavirus [SARS-CoV] and SARS-CoV-2) bind to their target cells through angiotensin-converting enzyme 2 (ACE2), which is expressed by epithelial cells of the lung, intestine, kidney, and blood vessels. 4 The expression of ACE2 is substantially increased in patients with type 1 or type 2 diabetes, who are treated with ACE inhibitors and angiotensin II type-I receptor blockers (ARBs). 4 Hypertension is also treated with ACE inhibitors and ARBs, which results in an upregulation of ACE2. 5 ACE2 can also be increased by thiazolidinediones and ibuprofen. These data suggest that ACE2 expression is increased in diabetes and treatment with ACE inhibitors and ARBs increases ACE2 expression. Consequently, the increased expression of ACE2 would facilitate infection with COVID-19. We therefore hypothesise that diabetes and hypertension treatment with ACE2-stimulating drugs increases the risk of developing severe and fatal COVID-19. If this hypothesis were to be confirmed, it could lead to a conflict regarding treatment because ACE2 reduces inflammation and has been suggested as a potential new therapy for inflammatory lung diseases, cancer, diabetes, and hypertension. A further aspect that should be investigated is the genetic predisposition for an increased risk of SARS-CoV-2 infection, which might be due to ACE2 polymorphisms that have been linked to diabetes mellitus, cerebral stroke, and hypertension, specifically in Asian populations. Summarising this information, the sensitivity of an individual might result from a combination of both therapy and ACE2 polymorphism. We suggest that patients with cardiac diseases, hypertension, or diabetes, who are treated with ACE2-increasing drugs, are at higher risk for severe COVID-19 infection and, therefore, should be monitored for ACE2-modulating medications, such as ACE inhibitors or ARBs. Based on a PubMed search on Feb 28, 2020, we did not find any evidence to suggest that antihypertensive calcium channel blockers increased ACE2 expression or activity, therefore these could be a suitable alternative treatment in these patients. © 2020 Juan Gaertner/Science Photo Library 2020 Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
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            Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19

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              Angiotensin receptor blockers as tentative SARS‐CoV‐2 therapeutics

              Abstract At the time of writing this commentary (February 2020), the coronavirus COVID‐19 epidemic has already resulted in more fatalities compared with the SARS and MERS coronavirus epidemics combined. Therapeutics that may assist to contain its rapid spread and reduce its high mortality rates are urgently needed. Developing vaccines against the SARS‐CoV‐2 virus may take many months. Moreover, vaccines based on viral‐encoded peptides may not be effective against future coronavirus epidemics, as virus mutations could make them futile. Indeed, new Influenza virus strains emerge every year, requiring new immunizations. A tentative suggestion based on existing therapeutics, which would likely be resistant to new coronavirus mutations, is to use available angiotensin receptor 1 (AT1R) blockers, such as losartan, as therapeutics for reducing the aggressiveness and mortality from SARS‐CoV‐2 virus infections. This idea is based on observations that the angiotensin‐converting enzyme 2 (ACE2) very likely serves as the binding site for SARS‐CoV‐2, the strain implicated in the current COVID‐19 epidemic, similarly to strain SARS‐CoV implicated in the 2002–2003 SARS epidemic. This commentary elaborates on the idea of considering AT1R blockers as tentative treatment for SARS‐CoV‐2 infections, and proposes a research direction based on datamining of clinical patient records for assessing its feasibility.
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                Author and article information

                Journal
                J Bras Nefrol
                J Bras Nefrol
                jbn
                Jornal Brasileiro de Nefrologia
                Sociedade Brasileira de Nefrologia
                0101-2800
                2175-8239
                26 August 2020
                2020
                : 42
                : 2 Suppl 1
                : 47-48
                Affiliations
                [1 ]Pontifícia Universidade Católica de São Paulo, Faculdade de Ciências Médicas e da Saúde, São Paulo, SP, Brazil.
                [2 ]Sociedade Brasileira de Nefrologia, Departamento de Hipertensão, São Paulo, SP, Brazil.
                Author notes
                Correspondence to: Cibele Isaac Saad Rodrigues E-mail: cisaad@ 123456pucsp.br ; cibele.sr@ 123456gmail.com
                Author information
                http://orcid.org/0000-0001-9490-7997
                Article
                2175-8239-JBN-2020-S112
                10.1590/2175-8239-JBN-2020-S112
                7479982
                e5c38a0a-c032-4708-abe8-fb93ee69164d

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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                coronavirus infections,hypertension,renin-angiotensin system,infecções por coronavírus,hipertensão,sistema renina-angiotensina

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