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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">TkxNRNcrXLxdmGBX5YqjFMF</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2020000600823</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2020005007206</article-id>
      <article-id pub-id-type="publisher-id">abc.20200215</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20200215</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Ponto de Vista</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>COVID-19: Dados Atualizados e sua Rela&#231;&#227;o Com o Sistema Cardiovascular</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0001-6929-8392</contrib-id>
          <name>
            <surname>Ferrari</surname>
            <given-names>Filipe</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgdiv2">Programa de P&#243;s-Gradua&#231;&#227;o em Cardiologia e Ci&#234;ncias Cardiovasculares</institution>
        <institution content-type="orgname">Universidade Federal do Rio Grande do Sul</institution>
        <institution content-type="orgdiv1">Hospital de Cl&#237;nicas de Porto Alegre</institution>
        <addr-line>
          <named-content content-type="city">Porto Alegre</named-content>
          <named-content content-type="state">RS</named-content>
        </addr-line>
        <country country="BR">Brasil</country>
        <institution content-type="original">Programa de P&#243;s-Gradua&#231;&#227;o em Cardiologia e Ci&#234;ncias Cardiovasculares, Universidade Federal do Rio Grande do Sul, Hospital de Cl&#237;nicas de Porto Alegre, Porto Alegre, RS &#8211; Brasil</institution>
      </aff>
      <author-notes>
        <corresp id="c01"> Correspond&#234;ncia: Filipe Ferrari &#8226; Universidade Federal do Rio Grande do Sul - Rua Mariana Prezzi, 617, 43B. CEP 95034460, Caxias do Sul, RS - Brasil E-mail: <email>ferrari.filipe88@gmail.com</email>
				</corresp>
        <fn fn-type="con">
          <p>Contribui&#231;&#227;o dos autores</p>
          <p>Concep&#231;&#227;o e desenho da pesquisa, Obten&#231;&#227;o de dados, An&#225;lise e interpreta&#231;&#227;o dos dados, Reda&#231;&#227;o do manuscrito e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Ferrari F.</p>
        </fn>
        <fn fn-type="conflict">
          <p>Potencial conflito de interesses</p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>11</day>
        <month>05</month>
        <year>2020</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>05</month>
        <year>2020</year>
      </pub-date>
      <volume>114</volume>
      <issue>5</issue>
      <fpage>823</fpage>
      <lpage>826</lpage>
      <history>
        <date date-type="received">
          <day>19</day>
          <month>03</month>
          <year>2020</year>
        </date>
        <date date-type="rev-recd">
          <day>03</day>
          <month>04</month>
          <year>2020</year>
        </date>
        <date date-type="accepted">
          <day>03</day>
          <month>04</month>
          <year>2020</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p> 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. </license-p>
        </license>
      </permissions>
      <abstract>
        <title>Resumo</title>
        <p>Em dezembro de 2019, um novo coronav&#237;rus humano, chamado s&#237;ndrome respirat&#243;ria aguda grave do coronav&#237;rus 2 (SARS-CoV-2) ou nomeado doen&#231;a de coronav&#237;rus (COVID-19) pela Organiza&#231;&#227;o Mundial da Sa&#250;de, surgiu na cidade de Wuhan, China. Difundido globalmente, &#233; atualmente considerado pand&#234;mico, com aproximadamente 3 milh&#245;es de casos no mundo no final de abril. Seus sintomas incluem febre, tosse, dor de cabe&#231;a e falta de ar, esse &#250;ltimo considerado o sintoma principal. Por sua vez, acredita-se que haja uma rela&#231;&#227;o entre o COVID-19 e danos ao m&#250;sculo card&#237;aco, e pacientes com hipertens&#227;o e diabetes, por exemplo, parecem apresentar progn&#243;stico pior. Portanto, o COVID-19 pode piorar em indiv&#237;duos com condi&#231;&#245;es adversas subjacentes. Um n&#250;mero n&#227;o negligenci&#225;vel de pacientes internados com este v&#237;rus tinham doen&#231;as cardiovasculares ou cerebrovasculares. A resposta inflamat&#243;ria sist&#234;mica e dist&#250;rbios do sistema imunol&#243;gico durante a progress&#227;o da doen&#231;a podem estar por tr&#225;s dessa associa&#231;&#227;o. Al&#233;m disso, o v&#237;rus usa os receptores da enzima conversora da angiotensina (ECA), mais especificamente da ECA2, para penetrar nas c&#233;lulas; portanto, o uso de f&#225;rmacos inibidores de ECA e bloqueadores de receptores de angiotensina pode causar um aumento nestes receptores, assim facilitando a entrada do v&#237;rus na c&#233;lula. No entanto, n&#227;o h&#225; evid&#234;ncias cient&#237;ficas que ap&#243;iem a interrup&#231;&#227;o desses medicamentos. Considerando que s&#227;o fundamentais para o manejo de certas doen&#231;as cr&#244;nicas, os riscos e benef&#237;cios da sua retirada devem ser cuidadosamente ponderados neste cen&#225;rio. Finalmente, cardiologistas e profissionais de sa&#250;de devem estar cientes dos riscos de infec&#231;&#227;o e se proteger o m&#225;ximo poss&#237;vel, dormindo adequadamente e evitando longos turnos de trabalho.</p>
      </abstract>
      <kwd-group xml:lang="pt">
        <kwd>Coronavirus</kwd>
        <kwd>COVID-19</kwd>
        <kwd>S&#237;ndrome Respirat&#243;ria Aguda</kwd>
        <kwd>Doen&#231;as Cardiovasculares/complica&#231;&#245;es</kwd>
        <kwd>Miocardite</kwd>
        <kwd>Doen&#231;as Infecciosas</kwd>
        <kwd>Fatores de Risco/preven&#231;&#227;o e controle</kwd>
      </kwd-group>
      <counts>
        <fig-count count="0"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="25"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>Em dezembro 2019, na cidade de Wuhan, China, houve uma explos&#227;o de casos de pneumonia causados por um novo coronav&#237;rus, chamado s&#237;ndrome respirat&#243;ria aguda grave do coronav&#237;rus 2 (SARS-CoV-2),<sup><xref ref-type="bibr" rid="B1">1</xref></sup> identificado como o agente que causa a doen&#231;a de coronav&#237;rus (COVID-19), nome oficialmente adotado pela Organiza&#231;&#227;o Mundial da Sa&#250;de. O COVID-19 &#233; uma condi&#231;&#227;o que pode afetar os pulm&#245;es, o trato respirat&#243;rio e outros sistemas. Dados filogen&#233;ticos sugerem uma origem zoon&#243;tica,<sup><xref ref-type="bibr" rid="B2">2</xref></sup> e tem sido demonstrado que a transmiss&#227;o do v&#237;rus se d&#225; de pessoa para pessoa. Tem sido detectado em escarro, saliva, e zaragatoas da garganta e nasofar&#237;ngeas.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Portanto, pode espalhar-se por meio de pequenas got&#237;culas liberadas pelo nariz e pela boca de indiv&#237;duos infectados. Os sintomas mais observados incluem febre, fadiga, tosse seca, congest&#227;o das vias a&#233;reas superiores, produ&#231;&#227;o de escarro, mialgia/artralgia com linfopenia e tempo prolongado de protrombina.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> No entanto, um dos sintomas principais &#233; falta de ar.</p>
      <p>Embora ainda sejam pouco conhecidas as evid&#234;ncias sobre os efeitos espec&#237;ficos do COVID-19 no sistema cardiovascular, h&#225; relatos de arritmias, les&#227;o card&#237;aca aguda, taquicardia e uma alta carga de doen&#231;a cardiovascular concomitantes nos indiv&#237;duos infectados, particularmente naqueles com mais comorbidades e fatores de risco que necessitam cuidados mais intensivos.<sup><xref ref-type="bibr" rid="B5">5</xref></sup></p>
      <p>O diagn&#243;stico de SARS-CoV-2 pode ser feito pela morfologia microsc&#243;pica, mas o m&#233;todo atualmente considerado o padr&#227;o-ouro &#233; a detec&#231;&#227;o de &#225;cido nucl&#233;ico em zaragatoa nasal, amostras da garganta ou outras amostras do trato respirat&#243;rio por rea&#231;&#227;o em cadeia da polimerase (RCP) em tempo real, que &#233; subsequentemente confirmado pelo sequenciamento de pr&#243;xima gera&#231;&#227;o.<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
      <p>Finalmente, &#233; necess&#225;rio observar que o melhor tratamento continua sendo a preven&#231;&#227;o, e medidas simples, tais como lavar as m&#227;os com sab&#227;o, utilizar &#225;lcool em gel e desinfetar superf&#237;cies como celulares, desempenham um papel essencial na redu&#231;&#227;o da propaga&#231;&#227;o do v&#237;rus.</p>
      <sec>
        <title>Epidemiologia</title>
        <sec>
          <title>Adultos e Idosos</title>
          <p>Dados mais recentes indicam que at&#233; o dia 23 de abril o n&#250;mero de casos confirmados de COVID-19 excediam 2.700.000 no mundo.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> Em 30 de janeiro de 2020, 9.976 casos de COVID-19 haviam sido relatados em pelo menos 21 pa&#237;ses.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> Um m&#234;s depois, foram confirmados 83.652 casos, com 2.791 &#243;bitos (mortalidade de 3,4%).<sup><xref ref-type="bibr" rid="B9">9</xref></sup> Foram relatados casos em 24 pa&#237;ses, em 5 continentes.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> No Brasil, especificamente, at&#233; 3 de mar&#231;o, haviam sido registrados 488 casos suspeitos, em 23 estados.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> Adicionalmente, at&#233; 23 de abril haviam sido confirmados aproximadamente 49.500 casos e 3.313 &#243;bitos por COVID-19 no Brasil.<sup><xref ref-type="bibr" rid="B12">12</xref></sup> Na It&#225;lia, em 20 fevereiro, um homem jovem na regi&#227;o de Lombardia foi internado com pneumonia at&#237;pica que mais tarde provou ser COVID-19. Durante as 24 horas seguintes, houve mais 36 casos, nenhum dos quais havia tido contato com o primeiro paciente ou com outros casos confirmados de COVID-19.<sup><xref ref-type="bibr" rid="B13">13</xref></sup> Infelizmente, apesar de medidas agressivas de conten&#231;&#227;o, a doen&#231;a continua a se espalhar e o n&#250;mero de pacientes afetados est&#225; aumentando. A taxa de letalidade n&#227;o est&#225; baixa, e predomina em pacientes idosos.<sup><xref ref-type="bibr" rid="B12">12</xref></sup> Portanto, aten&#231;&#227;o especial deve ser dada a essa popula&#231;&#227;o.</p>
          <p>At&#233; 23 de abril o mundo j&#225; havia registrado 2.707.356 casos de COVID-19, incluindo 83.880 casos na China. Dos 190.743 &#243;bitos da doen&#231;a at&#233; esta data, 4.636 ocorreram na China. J&#225; a Europa tinha registrado 1.193.276 casos, com 114.259 &#243;bitos,<sup><xref ref-type="bibr" rid="B7">7</xref></sup> tornando-se a regi&#227;o com o maior aumento de novas infec&#231;&#245;es a cada 24 horas. V&#225;rias regi&#245;es tamb&#233;m registraram seus primeiros casos, incluindo Som&#225;lia, Benin, Lib&#233;ria e Bahamas.<sup><xref ref-type="bibr" rid="B14">14</xref></sup></p>
          <p>Existem incertezas sobre as estimativas do n&#250;mero real de pessoas infectadas, que seria crucial para determinar a severidade da infec&#231;&#227;o e a incid&#234;ncia de casos leves ou assintom&#225;ticos, bem como a sua poss&#237;vel transmiss&#227;o.<sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
        </sec>
        <sec>
          <title>Crian&#231;as</title>
          <p>Fatores epidemiol&#243;gicos do COVID-19 entre crian&#231;as s&#227;o escassos. Por meio de an&#225;lise retrospectiva de crian&#231;as com uma idade m&#233;dia de 7 anos inclu&#237;das no Centro Chin&#234;s para Controle e Preven&#231;&#227;o de Doen&#231;as entre 16 janeiro e 8 fevereiro 2020, Dong et al.<sup><xref ref-type="bibr" rid="B16">16</xref></sup> observaram que houve 731 casos confirmados no laborat&#243;rio e 1.412 casos suspeitos. Significativamente, mais de 90% destas crian&#231;as eram assintom&#225;ticas ou apresentaram apenas sintomas leves ou moderados. Esses dados chamam aten&#231;&#227;o para o fato de que n&#227;o somente adultos e idosos mas tamb&#233;m crian&#231;as de qualquer idade s&#227;o suscet&#237;veis ao COVID-19. Por este motivo, aten&#231;&#227;o e cuidados devem ser direcionados para a popula&#231;&#227;o inteira, sem distin&#231;&#227;o.</p>
        </sec>
      </sec>
    </sec>
    <sec>
      <title>COVID-19 e o Sistema Cardiovascular</title>
      <p>Infec&#231;&#245;es respirat&#243;rias e influenza podem desempenhar um papel importante no aumento a curto prazo do risco de infarto do mioc&#225;rdio e acidente vascular cerebral isqu&#234;mico.<sup><xref ref-type="bibr" rid="B17">17</xref></sup> SARS-CoV-2 possui uma patogenicidade que pode aumentar danos no mioc&#225;rdio causado por esta infec&#231;&#227;o viral. Os dados sugerem que les&#227;o card&#237;aca aguda, choque e arritmia estavam presentes em 7,2%, 8,7% e 16,7% dos pacientes, respectivamente, e a sua preval&#234;ncia era mais alta entre pacientes que necessitaram cuidados intensivos.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> Baseado no fato de que o v&#237;rus pode causar danos ao sistema cardiovascular, aten&#231;&#227;o cuidadosa deve ser dada &#224; prote&#231;&#227;o cardiovascular durante o tratamento para COVID-19.<sup><xref ref-type="bibr" rid="B18">18</xref></sup> De fato, doen&#231;as cardiovasculares e hipertens&#227;o foram associadas a uma taxa de letalidade aumentada de COVID-19 na China.<sup><xref ref-type="bibr" rid="B19">19</xref></sup></p>
      <p>Les&#227;o do mioc&#225;rdio associada a SARS-CoV-2 foi relatada em 5 dos primeiros 41 pacientes diagnosticados com COVID-19 em Wuhan, os quais apresentaram n&#237;veis de troponina card&#237;aca I de alta sensibilidade &gt; 28 pg/ml.<sup><xref ref-type="bibr" rid="B20">20</xref></sup> Em outro estudo, realizado em 2019, Panhwar et al.<sup><xref ref-type="bibr" rid="B21">21</xref></sup> observaram que infec&#231;&#227;o concomitante &#224; influenza aumentou os riscos de pacientes internados com insufici&#234;ncia card&#237;aca. Em uma pesquisa de 25 pacientes que haviam recuperado de infec&#231;&#227;o por SARS-CoV-1, quase a metade apresentou altera&#231;&#245;es no sistema cardiovascular, e 60% apresentou dist&#250;rbios no metabolismo da glicose.<sup><xref ref-type="bibr" rid="B22">22</xref></sup> Outro estudo incluiu 1.099 pacientes com COVID-19 confirmado, dos quais 173 apresentaram doen&#231;a severa, com comorbidades de hipertens&#227;o (23,7%), diabetes mellitus (16,2%), doen&#231;as coron&#225;rias (5,8%) e doen&#231;a cerebrovascular (2,3%).<sup><xref ref-type="bibr" rid="B23">23</xref></sup></p>
      <p>Em uma avalia&#231;&#227;o de dados de 138 pacientes internados por COVID-19 na China, o tempo mediano entre o primeiro sintoma e a dispneia foi de 5 dias, e de 7 dias entre o primeiro sintoma e a interna&#231;&#227;o hospitalar. A tomografia computadorizada do t&#243;rax mostrou sombras fragmentadas bilaterais ou opacidade de vidro fosco nos pulm&#245;es de todos os pacientes. Aproximadamente 90% dos pacientes receberam terapia antiviral com oseltamivir, e mais de 60% receberam terapia antibacteriana com moxifloxacina. Trinta e seis paciente foram transferidos para a unidade de terapia intensiva devido a complica&#231;&#245;es, incluindo s&#237;ndrome do desconforto respirat&#243;rio agudo (61,1%), arritmia (44,4%) e choque (30,6%). Os pacientes que necessitaram cuidados intensivos tinham idade mais avan&#231;ada e maior probabilidade de apresentar comorbidades subjacentes, em adi&#231;&#227;o &#224; dispneia. Em 3 fevereiro, 34% haviam recebido alta hospitalar e 6 morreram, representando uma mortalidade geral de 4,3%.<sup><xref ref-type="bibr" rid="B10">10</xref></sup></p>
      <p>Em pacientes com COVID-19, a incid&#234;ncia de sintomas cardiovasculares &#233; alta, devido &#224; resposta inflamat&#243;ria sist&#234;mica e dist&#250;rbios do sistema imunol&#243;gico durante a progress&#227;o da doen&#231;a. Por este motivo, pacientes com doen&#231;as cardiovasculares subjacentes que s&#227;o infectados por COVID-19 podem apresentar progn&#243;stico pior. Aten&#231;&#227;o especial deve, portanto, ser dada &#224; prote&#231;&#227;o cardiovascular durante o tratamento de COVID-19.</p>
    </sec>
    <sec>
      <title>Receptores da Enzima conversora da Angiotensina e Bloqueadores de Receptores de Angiotensina</title>
      <p>O COVID-19 usa receptores da enzima conversora da angiotensina (ECA), mais especificamente a ECA2, para penetrar nas c&#233;lulas. Tem sido hipotetizado que o uso de inibidores de ECA e bloqueadores de receptores de angiotensina (BRAs) possam aumentar esses receptores, assim facilitando a penetra&#231;&#227;o do v&#237;rus.<sup><xref ref-type="bibr" rid="B24">24</xref></sup></p>
      <p>Em uma nota recente, a Sociedade Brasileira de Cardiologia enfatizou dados sobre a import&#226;ncia de tais f&#225;rmacos, como inibidores de ECA e BRAs, uma vez que n&#227;o h&#225; evid&#234;ncia clara apoiando a associa&#231;&#227;o entre a terapia com esses medicamentos e progn&#243;stico piorado da doen&#231;a.<sup><xref ref-type="bibr" rid="B25">25</xref></sup> Portanto, recomenda-se que os m&#233;dicos cuidadosamente avaliem a rela&#231;&#227;o risco-benef&#237;cio antes de suspender os medicamentos, visto que s&#227;o pilares fundamentais para o manejo de doen&#231;as cr&#244;nicas, como hipertens&#227;o e insufici&#234;ncia card&#237;aca. Da mesma forma, pacientes n&#227;o devem interromper seu uso indiscriminadamente, sem antes consultar seus m&#233;dicos.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Considera&#231;&#245;es finais</title>
      <p>O coronav&#237;rus &#233; uma fam&#237;lia de v&#237;rus que causam infec&#231;&#245;es respirat&#243;rias. O COVID-19 &#233; uma doen&#231;a grave que requer cuidados especiais. Indiv&#237;duos que apresentam febre, tosse e falta de ar devem procurar atendimento m&#233;dico. Ao contr&#225;rio do que muitos acreditam, o COVID-19 n&#227;o &#233; uma doen&#231;a restrita aos idosos; jovens e crian&#231;as tamb&#233;m podem ser infectados. Por&#233;m, pacientes idosos que t&#234;m doen&#231;a cardiovascular infectados por COVID-19 podem apresentar progn&#243;stico pior. Lavar as m&#227;os frequentemente, usar &#225;lcool em gel, cobrir o nariz com a parte interna do bra&#231;o e evitar ambientes aglomerados podem desempenhar um papel importante na redu&#231;&#227;o da propaga&#231;&#227;o do v&#237;rus e do agravamento da doen&#231;a, especialmente em pacientes com doen&#231;a cardiovascular.</p>
    </sec>
  </body>
  <back>
    <ref-list>
      <title>Refer&#234;ncias</title>
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      <fn fn-type="other">
        <p>Vincula&#231;&#227;o acad&#234;mica</p>
        <p>Programa de P&#243;s-Gradua&#231;&#227;o em Cardiologia e Ci&#234;ncias Cardiovasculares, Universidade Federal do Rio Grande do Sul, Hospital de Cl&#237;nicas de Porto Alegre.</p>
      </fn>
      <fn fn-type="other">
        <p>Aprova&#231;&#227;o &#233;tica e consentimento informado</p>
        <p>Este artigo n&#227;o cont&#233;m estudos com humanos ou animais realizados por nenhum dos autores.</p>
      </fn>
    </fn-group>
    <fn-group>
      <fn fn-type="supported-by">
        <p>Fontes de financiamento</p>
        <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
      </fn>
    </fn-group>
  </back>
  <sub-article article-type="translation" id="TRen" xml:lang="en">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Viewpoint</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>COVID-19: Updated Data and its Relation to the Cardiovascular System</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">000-0001-6929-8392</contrib-id>
          <name>
            <surname>Ferrari</surname>
            <given-names>Filipe</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1001">
        <label>1</label>
        <country country="BR">Brazil</country>
        <institution content-type="original">Graduate Program in Cardiology and Cardiovascular Sciences, Universidade Federal do Rio Grande do Sul, Hospital de Cl&#237;nicas de Porto Alegre, Porto Alegre, RS &#8211; Brazil</institution>
      </aff>
      <author-notes>
        <corresp id="c01001">Mailing Address: Filipe Ferrari &#8226; Universidade Federal do Rio Grande do Sul - Rua Mariana Prezzi, 617, 43B. Postal Code 95034460, Caxias do Sul, RS - Brazil E-mail: ferrari.filipe88@gmail.com</corresp>
        <fn fn-type="con">
          <p>Author contributions</p>
          <p>Conception and design of the research, Acquisition of data, Analysis and interpretation of the data, Writing of the manuscript and Critical revision of the manuscript for intellectual content: Ferrari F.</p>
        </fn>
        <fn fn-type="conflict">
          <p>Potential Conflict of Interest</p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Abstract</title>
        <p>In December 2019, a new human coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coronavirus disease 2019 (COVID-19) by the World Health Organization, emerged in the city of Wuhan, China. Spreading globally, it is now considered pandemic, with approximately 3 million cases worldwide at the end of April. Its symptoms include fever, cough, and headache, but the main one is shortness of breath. In turn, it is believed that there is a relationship between COVID-19 and damage to the heart muscle, and hypertensive and diabetic patients, for example, seem to have worse prognosis. Therefore, COVID-19 may worsen in individuals with underlying adverse conditions, and a not negligible number of patients hospitalized with this virus had cardiovascular or cerebrovascular diseases. Systemic inflammatory response and immune system disorders during disease progression may be behind this association. In addition, the virus uses angiotensin-converting enzyme (ACE) receptors, more precisely ACE2, to penetrate the cell; therefore, the use of ACE inhibitor drugs and angiotensin receptor blockers could cause an increase in these receptors, thus facilitating the entry of the virus into the cell. There is, however, no scientific evidence to support the interruption of these drugs. Since they are fundamental for certain chronic diseases, the risk and benefit of their withdrawal in this scenario should be carefully weighed. Finally, cardiologists and health professionals should be aware of the risks of infection and protect themselves as much as possible, sleeping properly and avoiding long working hours.</p>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>Coronavirus</kwd>
        <kwd>COVID 19</kwd>
        <kwd>Acute Respiratory Syndrome</kwd>
        <kwd>cardiovascular Diseases/complications</kwd>
        <kwd>Myocarditis</kwd>
        <kwd>Infectious Diseases</kwd>
        <kwd>Risk Factors/prevention and control</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>In December 2019, in the city of Wuhan, China, there was an explosion of cases of pneumonia caused by a novel coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),<sup><xref ref-type="bibr" rid="B1">1</xref></sup> identified as the agent that causes the disease called coronavirus disease 2019 (COVID-19), which is the name officially adopted by the World Health Organization. COVID-19 is a condition that can affect the lungs, respiratory tract, and others systems. Phylogenetic data imply a zoonotic origin,<sup><xref ref-type="bibr" rid="B2">2</xref></sup> and it has been shown that the transmission of the virus occurs from person to person. It has been detected in sputum, saliva, throat and nasopharyngeal swabs.<sup><xref ref-type="bibr" rid="B3">3</xref></sup> Therefore, it can spread through small droplets released from the nose and mouth of infected individuals. Some of the most observed symptoms are fever, fatigue, dry cough, upper airway congestion, sputum production, myalgia/arthralgia with lymphopenia, and prolonged prothrombin time.<sup><xref ref-type="bibr" rid="B4">4</xref></sup> However, one of the main symptoms may be shortness of breath.</p>
        <p>Although evidence on the specific effects of COVID-19 on the cardiovascular system is still little-known, there are reports of arrhythmias, acute cardiac injury, tachycardia, and a high burden of concomitant cardiovascular disease in infected individuals, particularly in those with higher comorbidities and risk factors who require more intensive care.<sup><xref ref-type="bibr" rid="B5">5</xref></sup></p>
        <p>Diagnosis of SARS-CoV-2 can be made by electron microscopy morphology, but the method currently considered the gold standard is detection of nucleic acid in nasal swab, throat samples, or other respiratory tract samples by real time polymerase chain reaction (PCR), which is later confirmed by next generation sequencing.<sup><xref ref-type="bibr" rid="B6">6</xref></sup></p>
        <p>Finally, it should be noted that the best treatment is still prevention, and simple measures such as washing hands with soap, using alcohol gel, and disinfecting surfaces such as cell phones play an essential role in reducing the spread of the virus.</p>
        <sec>
          <title>Epidemiology</title>
          <sec>
            <title>Adults and the Elderly</title>
            <p>More recent data indicate that by April 23 the number of confirmed cases of COVID-19 exceeded 2,700,000 worldwide.<sup><xref ref-type="bibr" rid="B7">7</xref></sup> On January 30, 2020, 9,976 cases of COVID-19 had been reported in at least 21 countries.<sup><xref ref-type="bibr" rid="B8">8</xref></sup> One month later, 83,652 cases were confirmed, with 2,791 deaths (3.4% mortality).<sup><xref ref-type="bibr" rid="B9">9</xref></sup> Cases were reported in 24 countries on 5 continents.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> In Brazil, specifically, by March 3, 488 suspected cases had been registered, in 23 states.<sup><xref ref-type="bibr" rid="B11">11</xref></sup> In addition, as of April 23, approximately 49,500 cases and 3,313 deaths had been confirmed by COVID-19 in Brazil.<sup><xref ref-type="bibr" rid="B12">12</xref></sup> In Italy, on February 20, a young man in the Lombardy Region was hospitalized with an atypical pneumonia that later proved to be COVID-19. In the following 24 hours, there were 36 more cases, none of which had been in contact with the first patient or anyone known to have COVID-19.<sup><xref ref-type="bibr" rid="B13">13</xref></sup> Unfortunately, despite aggressive containment efforts, the disease continues to spread and the number of affected patients is increasing. The fatality rate is not low, and it is dominated by elderly patients.<sup><xref ref-type="bibr" rid="B12">12</xref></sup> Therefore, special attention should also be given to this population.</p>
            <p>By April 23, the world had already registered 2,707,356 cases of COVID-19, including 83,880 cases in China. Of the 190,743 deaths from the disease as of April 23, 4,636 occurred in China. Europe had registered 1,193,276 cases, with 114,259 deaths,<sup><xref ref-type="bibr" rid="B7">7</xref></sup> making it the region with the largest 24-hour increase in new infections. Several regions have also registered their first cases, including Somalia, Benin, Liberia, and the Bahamas.<sup><xref ref-type="bibr" rid="B14">14</xref></sup></p>
            <p>There are uncertainties about the estimates of the true number of infected people, which is crucial to determine the severity of infection and the incidence of mild or asymptomatic cases, as well as their possible transmission.<sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
          </sec>
          <sec>
            <title>Children</title>
            <p>Epidemiological factors of COVID-19 among children are scarce. Dong et al.<sup><xref ref-type="bibr" rid="B16">16</xref></sup> through a retrospective analysis of children with a mean age of 7 years included in the Chinese Center for Disease Control and Prevention from January 16 to February 8, 2020, found that there were 731 confirmed cases in the laboratory and 1,412 suspected cases. Importantly, more than 90% of these individuals were asymptomatic or had only mild or moderate symptoms. These data draw attention to the fact that not only adults and the elderly, but also children of any age are susceptible to COVID-19. Therefore, attention and care should be directed to the entire population, without distinction.</p>
          </sec>
        </sec>
      </sec>
      <sec>
        <title>COVID-19 and the Cardiovascular System</title>
        <p>Respiratory infections and influenza can play an important role in the short-term increase of risk of myocardial infarction and ischemic stroke.<sup><xref ref-type="bibr" rid="B17">17</xref></sup> SARS-CoV-2 has a pathogenicity that can increase damage to the myocardium caused by this viral infection. The data suggest that acute cardiac injury, shock, and arrhythmia were present in 7.2%, 8.7%, and 16.7% of patients, respectively, and their prevalence was higher among patients requiring intensive care.<sup><xref ref-type="bibr" rid="B10">10</xref></sup> Based on the fact that the virus can cause damage to the cardiovascular system, careful attention should be given to cardiovascular protection during treatment of COVID-19.<sup><xref ref-type="bibr" rid="B18">18</xref></sup> In fact, cardiovascular disease and hypertension have been associated with an increased case fatality rate of COVID-19 in China.<sup><xref ref-type="bibr" rid="B19">19</xref></sup></p>
        <p>Myocardial injury associated with SARS-CoV-2 was reported in 5 of the first 41 patients diagnosed with COVID-19 in Wuhan, who had high-sensitivity cardiac troponin I levels &gt; 28 pg/ml.<sup><xref ref-type="bibr" rid="B20">20</xref></sup> In another study, conducted in 2019, Panhwar et al.<sup><xref ref-type="bibr" rid="B21">21</xref></sup> observed that concomitant infection by influenza increased risks in hospitalized patients with heart failure. In a survey of 25 patients who had recovered from SARS-CoV-1 infection, almost half of them had changes in the cardiovascular system, and 60% had glucose metabolism disorders.<sup><xref ref-type="bibr" rid="B22">22</xref></sup> Another study included 1,099 patients with confirmed COVID-19, 173 of whom had severe disease, with comorbidities of hypertension (23.7%), diabetes mellitus (16.2%), coronary diseases (5.8%), and cerebrovascular disease (2.3%).<sup><xref ref-type="bibr" rid="B23">23</xref></sup></p>
        <p>When evaluating data from 138 patients hospitalized for COVID-19 in China, the median time between the first symptom and dyspnea was 5 days, and 7 days between the first symptom and hospital admission. Computed tomography of the chest showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Approximately 90% of patients received antiviral therapy with oseltamivir, and more than 60% received antibacterial therapy with moxifloxacin. Thirty-six patients were transferred to the intensive care unit due to complications, including acute respiratory distress syndrome (61.1%), arrhythmia (44.4%), and shock (30.6%). Patients who required intensive care were older and more likely to have underlying comorbidities, as well as dyspnea. On February 3, 34% were discharged and 6 died, representing an overall mortality of 4.3%.<sup><xref ref-type="bibr" rid="B10">10</xref></sup></p>
        <p>In COVID-19 patients, the incidence of cardiovascular symptoms is high, due to systemic inflammatory response and immune system disorders during disease progression. Patients with underlying cardiovascular disease who are infected by COVID-19 may then have worse prognosis. Special attention should, therefore, be given to cardiovascular protection during treatment for COVID-19.</p>
      </sec>
      <sec>
        <title>Angiotensin-Converting Enzyme Receptors and Angiotensin Receptor Blockers</title>
        <p>COVID-19 uses angiotensin-converting enzyme (ACE) receptors, more precisely ACE2, to penetrate the cell. It has thus been hypothesized that the use of ACE inhibitors and angiotensin receptor blockers (ARB) could increase these receptors, facilitating the penetration of the virus.<sup><xref ref-type="bibr" rid="B24">24</xref></sup></p>
        <p>In a note, the Brazilian Society of Cardiology recently emphasized data on the importance of the use of drugs such as ACE inhibitors and ARB, as there is no clear evidence to support the association between therapy with these drugs and worsening prognosis of the disease.<sup><xref ref-type="bibr" rid="B25">25</xref></sup> It is thus recommended that physicians carefully evaluate the risk-benefit balance before suspending drugs, given that they are fundamental pillars for management of chronic diseases, such as hypertension and heart failure. Likewise, patients should not interrupt their use indiscriminately without first consulting their physicians.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Final considerations</title>
        <p>Coronavirus is a family of viruses that cause respiratory infections. COVID-19 is a serious disease, which requires special care. Individuals who present fever, cough, and shortness of breath should seek medical service. Contrary to what many may believe, COVID-19 is not a disease restricted to older adults; young people and children can also become infected. However, older patients who have cardiovascular disease and are infected with COVID-19 may have worse prognosis. Frequent hand washing, use of alcohol gel, covering the nose with the inside of the arm, and avoiding crowded environments can play an important role in reducing the spread of the virus and aggravation of the disease, especially in patients with cardiovascular disease.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="other">
          <p>Study Association</p>
          <p>This study is not associated with any thesis or dissertation work.</p>
        </fn>
        <fn fn-type="other">
          <p>Ethics approval and consent to participate</p>
          <p>This article does not contain any studies with human participants or animals performed by any of the authors.</p>
        </fn>
      </fn-group>
      <fn-group>
        <fn fn-type="supported-by">
          <p>Sources of Funding</p>
          <p>There were no external funding sources for this study.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
