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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 specific-use="scielo-v3" pub-id-type="publisher-id">4VGN7GTfvbX57qdYycpNqzh</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S0066-782X2022000400783</article-id>
      <article-id pub-id-type="publisher-id">abc.20210469</article-id>
      <article-id pub-id-type="doi">10.36660/abc.20210469</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Carta Cient&#237;fica</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Miocardite Aguda ap&#243;s a Vacina de mRNA contra a COVID-19</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-6894-648X</contrib-id>
          <name>
            <surname>Gomes</surname>
            <given-names>Daniel A.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-0881-053X</contrib-id>
          <name>
            <surname>Santos</surname>
            <given-names>Rita R.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Freitas</surname>
            <given-names>Pedro</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Paiva</surname>
            <given-names>Mariana S.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-5592-6199</contrib-id>
          <name>
            <surname>Ferreira</surname>
            <given-names>Jorge</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-1625-1459</contrib-id>
          <name>
            <surname>Trabulo</surname>
            <given-names>Marisa</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">Departamento de Cardiologia</institution>
        <institution content-type="orgdiv1">Hospital de Santa Cruz</institution>
        <institution content-type="orgname">Centro Hospitalar de Lisboa Ocidental</institution>
        <addr-line>
          <named-content content-type="city">Carnaxide</named-content>
        </addr-line>
        <country country="PT">Portugal</country>
        <institution content-type="original">Departamento de Cardiologia, Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental, Carnaxide &#8211; Portugal</institution>
      </aff>
      <author-notes>
        <corresp id="c01"> Correspond&#234;ncia: Daniel A. Gomes &#8226; Cardiology Department &#8211; Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental &#8211; 2790-134. Carnaxide &#8211; Portugal E-mail: <email>dgomes@chlo.min-saude.pt</email> </corresp>
        <fn fn-type="con">
          <p>Contribui&#231;&#227;o dos autores</p>
          <p>Concep&#231;&#227;o e desenho da pesquisa: Gomes DA, Ferreira J, Trabulo M; Obten&#231;&#227;o de dados: Gomes DA, Santos RR, Freitas P, Paiva MS; An&#225;lise e interpreta&#231;&#227;o dos dados e Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Gomes DA, Santos RR, Freitas P, Paiva MS, Ferreira J, Trabulo M; Reda&#231;&#227;o do manuscrito: Gomes DA.</p>
        </fn>
        <fn fn-type="conflict">
          <p>Potencial conflito de interesse</p>
          <p>N&#227;o h&#225; conflito com o presente artigo</p>
        </fn>
      </author-notes>
      <pub-date date-type="pub" publication-format="electronic">
        <day>29</day>
        <month>04</month>
        <year>2022</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <month>04</month>
        <year>2022</year>
      </pub-date>
      <volume>118</volume>
      <issue>4</issue>
      <fpage>783</fpage>
      <lpage>786</lpage>
      <history>
        <date date-type="received">
          <day>09</day>
          <month>06</month>
          <year>2021</year>
        </date>
        <date date-type="rev-recd">
          <day>14</day>
          <month>09</month>
          <year>2021</year>
        </date>
        <date date-type="accepted">
          <day>10</day>
          <month>11</month>
          <year>2021</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 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. </license-p>
        </license>
      </permissions>
      <kwd-group xml:lang="pt">
        <kwd>Coronavirus-19</kwd>
        <kwd>COVID-19</kwd>
        <kwd>Vacina/efeitos Adversos</kwd>
        <kwd>Imunogenicidade da Vacina</kwd>
        <kwd>Mimetismo Molecular</kwd>
        <kwd>Miocardite</kwd>
        <kwd>Diagn&#243;stico por Imagem</kwd>
      </kwd-group>
      <counts>
        <fig-count count="4"/>
        <table-count count="0"/>
        <equation-count count="0"/>
        <ref-count count="16"/>
        <page-count count="4"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introdu&#231;&#227;o</title>
      <p>A vacina&#231;&#227;o &#233; um dos maiores desenvolvimentos da medicina moderna e constitui um grande avan&#231;o na preven&#231;&#227;o de doen&#231;as infecciosas.<sup><xref rid="B1" ref-type="bibr">1</xref></sup> Normalmente as vacinas s&#227;o eficazes e t&#234;m um excelente perfil de seguran&#231;a geral.<sup><xref rid="B2" ref-type="bibr">2</xref></sup>De fato, relatos de efeitos adversos graves ap&#243;s a vacina&#231;&#227;o s&#227;o extremamente raros e idiossincr&#225;ticos.<sup><xref rid="B2" ref-type="bibr">2</xref></sup></p>
      <p>Como o mecanismo de a&#231;&#227;o da vacina &#233; baseado na resposta imune do hospedeiro, uma estreita rela&#231;&#227;o com a autoimunidade n&#227;o pode ser desconsiderada.<sup><xref rid="B3" ref-type="bibr">3</xref></sup> Casos de reatogenicidade imunol&#243;gica, como s&#237;ndrome de Guillain-Barr&#233; e miocardite aguda ap&#243;s vacina&#231;&#227;o, foram relatados anteriormente.<sup><xref rid="B4" ref-type="bibr">4</xref>, <xref rid="B5" ref-type="bibr">5</xref></sup></p>
      <p>Relatamos o caso de um paciente jovem do sexo masculino que desenvolveu miocardite aguda ap&#243;s a vacina de mRNA contra SARS-CoV-2.</p>
    </sec>
    <sec>
      <title>Relato de caso</title>
      <p>Um homem de 32 anos foi hospitalizado com pr&#233;-s&#237;ncope e dor tor&#225;cica retroesternal opressiva. A dor perdurou por duas horas, n&#227;o havia irradia&#231;&#227;o e n&#227;o era alterada por movimentos respirat&#243;rios ou posi&#231;&#227;o. Ele apresentava febre (39&#186;C) e mialgia generalizada por dois dias, iniciando um dia ap&#243;s a administra&#231;&#227;o da segunda dose da vacina de mRNA contra a COVID-19. O paciente estava hemodinamicamente est&#225;vel e seu exame f&#237;sico na hospitaliza&#231;&#227;o foi normal, exceto pela presen&#231;a de febre. Negou epis&#243;dios recentes de dor tor&#225;cica, infec&#231;&#227;o do trato respirat&#243;rio ou gastrointestinal. N&#227;o fazia uso de drogas ou medicamentos e n&#227;o foram identificados fatores de risco ocupacionais ou recreativos.</p>
      <p>O paciente era saud&#225;vel, exceto por um hist&#243;rico de miopericardite idiop&#225;tica, que ocorreu treze anos antes. Nessa ocasi&#227;o, uma resson&#226;ncia magn&#233;tica card&#237;aca (RMC) realizada na fase aguda revelou realce tardio de gadol&#237;nio subepic&#225;rdico na parede lateral. O paciente recebeu alta e permaneceu est&#225;vel, em acompanhamento cl&#237;nico regular. A resolu&#231;&#227;o completa desses achados foi observada na RMC realizada com 1 ano de seguimento.</p>
      <p>Dadas as caracter&#237;sticas da dor tor&#225;cica em um paciente jovem com s&#237;ndrome viral concomitante, a miocardite foi considerada como diagn&#243;stico prov&#225;vel. O paciente apresentava par&#226;metros inflamat&#243;rios elevados (leucocitose e prote&#237;na C-reativa 4,6mg/dL) e biomarcadores mioc&#225;rdicos (troponina card&#237;aca de alta sensibilidade T 834ng/L e NT-proBNP 433pg/mL) no exame de sangue. A radiografia de t&#243;rax foi normal. O ECG demonstrou supradesnivelamento difuso do segmento ST c&#244;ncavo ( <xref rid="f01" ref-type="fig">figura 1A</xref> ). Na ecocardiografia transtor&#225;cica, a fra&#231;&#227;o de eje&#231;&#227;o do ventr&#237;culo esquerdo estava preservada (58%) e n&#227;o foram observadas anormalidades na contratilidade segmentar, embora o <italic>strain</italic> longitudinal global estivesse levemente reduzido (-17%). N&#227;o havia derrame peric&#225;rdico. A RMC revelou realce tardio subepic&#225;rdico nas paredes m&#233;dio-anterior, lateral e inferior ( <xref rid="f02" ref-type="fig">figura 2A</xref> ) acompanhado de aumento de T1 e T2 nativos nos segmentos m&#233;dio-anterior e lateral ( <xref rid="f02" ref-type="fig">figuras 2B</xref> e <xref rid="f02" ref-type="fig">2C</xref> ). N&#227;o foram observados sinais de inflama&#231;&#227;o peric&#225;rdica. A rea&#231;&#227;o em cadeia da polimerase (PCR, <italic>Polymerase Chain Reaction</italic> ) de swab nasal e orofar&#237;ngeo foi negativa em duas ocasi&#245;es diferentes para SARS-CoV-2. Dada a alta suspeita cl&#237;nica e um padr&#227;o de RMC consistente com miocardite aguda em um paciente sem fatores de risco cardiovascular conhecidos, a angiografia coron&#225;ria n&#227;o foi realizada.</p>
      <p>
        <fig id="f01">
          <label>Figura 1</label>
          <caption>
            <title>&#8211; ECG na hospitaliza&#231;&#227;o demonstrando supradesnivelamento difuso do segmento ST c&#244;ncavo (figura 1A) e ECG aos 3 meses de seguimento mostrando resolu&#231;&#227;o das anormalidades do segmento ST (figura 1B).</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-118-04-0783-10469-gf01.tif"/></fig>
      </p>
      <p>
        <fig id="f02">
          <label>Figura 2</label>
          <caption>
            <title>&#8211; Resson&#226;ncia magn&#233;tica card&#237;aca (RMC) na hospitaliza&#231;&#227;o demonstrando realce tardio de gadol&#237;nio subepic&#225;rdico nas paredes m&#233;dio-anterior, lateral e inferior (figura 2A), e aumento de T1 (figura 2B) e T2 (figura 2C) nativos. A RMC aos 3 meses de seguimento revelou melhora no padr&#227;o subepic&#225;rdico de realce tardio de gadol&#237;nio (figura 2D) e normaliza&#231;&#227;o do T1 (figura 2E) e T2 (figura 2F) nativos.</title>
          </caption>
          <graphic xlink:href="1678-4170-abc-118-04-0783-10469-gf02.tif"/></fig>
      </p>
      <p>O diagn&#243;stico de miocardite aguda foi considerado. O paciente recebeu alta tr&#234;s dias ap&#243;s a hospitaliza&#231;&#227;o e foi aconselhado a n&#227;o realizar atividade f&#237;sica intensa durante um per&#237;odo de 3 a 6 meses. Um ECG foi repetido ap&#243;s melhora cl&#237;nica e revelou normaliza&#231;&#227;o do supradesnivelamento do segmento ST ( <xref rid="f01" ref-type="fig">figura 1B</xref> ). Uma RMC aos 3 meses de seguimento demonstrou uma melhora significativa no padr&#227;o subepic&#225;rdico de realce tardio de gadol&#237;nio ( <xref rid="f02" ref-type="fig">figura 2D</xref> ) e normaliza&#231;&#227;o das anormalidades anteriormente observadas no mapeamento das sequ&#234;ncias T1 e T2 ( <xref rid="f02" ref-type="fig">figuras 2E</xref> e <xref rid="f02" ref-type="fig">2F</xref> ).</p>
    </sec>
    <sec sec-type="discussion">
      <title>Discuss&#227;o</title>
      <p>A miocardite &#233; uma doen&#231;a inflamat&#243;ria do mioc&#225;rdio causada por v&#225;rias condi&#231;&#245;es infecciosas e n&#227;o infecciosas.6 Sua apresenta&#231;&#227;o cl&#237;nica varia de forma ampla, de dor tor&#225;cica leve at&#233; choque cardiog&#234;nico ou arritmias ventriculares potencialmente fatais.<sup><xref rid="B6" ref-type="bibr">6</xref>, <xref rid="B7" ref-type="bibr">7</xref></sup> Embora a bi&#243;psia card&#237;aca continue sendo o padr&#227;o-ouro, n&#227;o &#233; rotineiramente realizada na pr&#225;tica cl&#237;nica para a maioria dos pacientes e, portanto, a RMC, ao preencher os Crit&#233;rios de Lake Louise modificados, &#233; extremamente &#250;til para estabelecer o diagn&#243;stico.<sup><xref rid="B6" ref-type="bibr">6</xref> - <xref rid="B8" ref-type="bibr">8</xref> </sup></p>
      <p>H&#225; poucos relatos de miocardite ap&#243;s vacina&#231;&#227;o. Embora houvesse algumas preocupa&#231;&#245;es iniciais sobre o desenvolvimento de doen&#231;a card&#237;aca inflamat&#243;ria em receptores de vacinas virais vivas, estudos mais recentes sugerem que seu risco geral n&#227;o &#233; aumentado.<sup><xref rid="B5" ref-type="bibr">5</xref>, <xref rid="B9" ref-type="bibr">9</xref></sup> De fato, em uma coorte com mais de 41.000 pacientes, apenas um caso de pericardite definitiva e nenhum caso de miocardite foram diagnosticados nos primeiros 42 dias ap&#243;s a vacina&#231;&#227;o.<sup><xref rid="B5" ref-type="bibr">5</xref></sup></p>
      <p>A introdu&#231;&#227;o de vacinas contra o SARS-CoV-2 &#233; um elemento fundamental para controlar a propaga&#231;&#227;o desta pandemia. Entre aqueles que receberam a vacina de mRNA contra a COVID-19 em ensaios cl&#237;nicos de larga escala, ela mostrou-se altamente eficaz e segura, sem relatos de efeitos cardiovasculares adversos significativos.<sup><xref rid="B10" ref-type="bibr">10</xref></sup> Sintomas sist&#234;micos relacionados &#224; reatogenicidade imunol&#243;gica foram comuns, principalmente leves a moderados, e mais frequentes ap&#243;s a segunda dose, com mediana de in&#237;cio de 1 a 2 dias ap&#243;s a aplica&#231;&#227;o da vacina.<sup><xref rid="B11" ref-type="bibr">11</xref></sup></p>
      <p>Relatamos o caso de um homem de 32 anos que desenvolveu miocardite aguda autolimitada ap&#243;s imuniza&#231;&#227;o contra a COVID-19. Este caso cl&#237;nico &#233; consistente com outros recentemente publicados.<sup><xref rid="B12" ref-type="bibr">12</xref> - <xref rid="B14" ref-type="bibr">14</xref> </sup> Como descrevemos, a miocardite aguda ap&#243;s a vacina&#231;&#227;o contra COVID-19 parece ser uma complica&#231;&#227;o potencialmente rara e autolimitada, afetando principalmente pacientes do sexo masculino jovens e saud&#225;veis dois a tr&#234;s dias ap&#243;s receber a segunda dose.</p>
      <p>Os mecanismos imunol&#243;gicos exatos que ligam a vacina ao desenvolvimento de miocardite aguda n&#227;o s&#227;o completamente claros. S&#237;ndrome autoinflamat&#243;ria, reatividade cruzada, mimetismo molecular e gera&#231;&#227;o de autoanticorpos em indiv&#237;duos suscet&#237;veis ou predispostos t&#234;m sido sugeridos como implicados na patog&#234;nese.<sup><xref rid="B13" ref-type="bibr">13</xref></sup> De fato, relatos anteriores evidenciaram o papel da rea&#231;&#227;o cruzada e do mimetismo nos fen&#244;menos autoimunes p&#243;s-vacina&#231;&#227;o.<sup><xref rid="B15" ref-type="bibr">15</xref></sup></p>
      <p>Embora outras etiologias como miocardite viral coincidente com o momento vacinal n&#227;o possam ser definitivamente exclu&#237;das, dada a associa&#231;&#227;o temporal, podemos levantar a hip&#243;tese de que a resposta imune &#224; vacina pode ter desencadeado a recorr&#234;ncia da miocardite neste paciente.</p>
      <p>Mais estudos s&#227;o necess&#225;rios para esclarecer melhor a epidemiologia, a fisiopatologia e os resultados cl&#237;nicos a longo prazo desses pacientes. Pesquisas futuras sobre esse assunto devem se concentrar em: (1) explorar fatores predisponentes e mecanismos fisiopatol&#243;gicos para o desenvolvimento de les&#227;o mioc&#225;rdica ap&#243;s a vacina&#231;&#227;o contra COVID-19 (incluindo mimetismo molecular, forma&#231;&#227;o de autoanticorpos e o papel de popula&#231;&#245;es espec&#237;ficas de c&#233;lulas imunes); (2) caracterizar altera&#231;&#245;es ultraestruturais e funcionais do mioc&#225;rdio, bem como biomarcadores card&#237;acos e fun&#231;&#227;o card&#237;aca; (3) caracterizar prospectivamente a apresenta&#231;&#227;o cl&#237;nica, a evolu&#231;&#227;o cl&#237;nica e os resultados em longo prazo desses pacientes.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclus&#245;es</title>
      <p>A miocardite aguda autolimitada pode ser um efeito adverso potencial e raro das vacinas de mRNA contra a COVID-19. Embora os m&#233;dicos devam estar cientes dessa possibilidade, de forma alguma devem desencorajar a vacina&#231;&#227;o, pois a an&#225;lise de risco-benef&#237;cio para a imuniza&#231;&#227;o contra a COVID-19 mostra um efeito ben&#233;fico consistente em todos os grupos.<sup><xref rid="B14" ref-type="bibr">14</xref>, <xref rid="B16" ref-type="bibr">16</xref></sup> Atualmente a vacina &#233; recomendada para todos com mais de 12 anos de idade.<sup><xref rid="B16" ref-type="bibr">16</xref></sup></p>
    </sec>
  </body>
  <back>
    <ref-list>
      <title>Refer&#234;ncias</title>
      <ref id="B1">
        <label>1</label>
        <mixed-citation>1.Andr&#233; F. Vaccinology: past achievements, present roadblocks and future promises. Vaccine.2003;21(7-8):593-5. DOI: <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/S0264-410X(02)00702-8">https://doi.org/10.1016/S0264-410X(02)00702-8</ext-link>.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Andr&#233;</surname>
              <given-names>F</given-names>
            </name>
          </person-group>
          <article-title>Vaccinology: past achievements, present roadblocks and future promises</article-title>
          <source> Vaccine </source>
          <year>2003</year>
          <volume>21</volume>
          <season>7-8</season>
          <fpage>593</fpage>
          <lpage>595</lpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1016/S0264-410X(02)00702-8">https://doi.org/10.1016/S0264-410X(02)00702-8</ext-link>
          </comment>
        </element-citation>
      </ref>
      <ref id="B2">
        <label>2</label>
        <mixed-citation>2.Dudley MZ, Halsey NA, Omer SB. The state of vaccine safety science: systematic reviews of the evidence. Lancet Infect Dis. 2020;20(5):e80-e89. DOI: 10.1016/S1473-3099(20)30130-4.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Dudley</surname>
              <given-names>MZ</given-names>
            </name>
            <name>
              <surname>Halsey</surname>
              <given-names>NA</given-names>
            </name>
            <name>
              <surname>Omer</surname>
              <given-names>SB</given-names>
            </name>
          </person-group>
          <article-title>The state of vaccine safety science: systematic reviews of the evidence</article-title>
          <source> Lancet Infect Dis </source>
          <year>2020</year>
          <volume>20</volume>
          <issue>5</issue>
          <fpage>e80</fpage>
          <lpage>e89</lpage>
          <issue-id pub-id-type="doi">10.1016/S1473-3099(20)30130-4.</issue-id>
        </element-citation>
      </ref>
      <ref id="B3">
        <label>3</label>
        <mixed-citation>3.Guimar&#227;es LE, Baker B, Perricone C, Shoenfeld Y. Vaccines, adjuvants and autoimmunity. Pharmacol Res. 2015;100:190-209. DOI: 10.1016/j.phrs.2015.08.003.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Guimar&#227;es</surname>
              <given-names>LE</given-names>
            </name>
            <name>
              <surname>Baker</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Perricone</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Shoenfeld</surname>
              <given-names>Y</given-names>
            </name>
          </person-group>
          <article-title>Vaccines, adjuvants and autoimmunity</article-title>
          <source> Pharmacol Res </source>
          <year>2015</year>
          <volume>100</volume>
          <fpage>190</fpage>
          <lpage>209</lpage>
          <issue-id pub-id-type="doi">10.1016/j.phrs.2015.08.003.</issue-id>
        </element-citation>
      </ref>
      <ref id="B4">
        <label>4</label>
        <mixed-citation>4.Salmon DA, Proschan M, Forshee R, Gargiullo P, Bleser W, Burwen DR, et al. Association between Guillain-Barr&#233; syndrome and influenza A (H1N1) 2009 monovalent inactivated vaccines in the USA: a meta-analysis. Lancet. 2013; 381(9876):1461-8. DOI: 10.1016/S0140-6736(12)62189-8.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Salmon</surname>
              <given-names>DA</given-names>
            </name>
            <name>
              <surname>Proschan</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Forshee</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Gargiullo</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Bleser</surname>
              <given-names>W</given-names>
            </name>
            <name>
              <surname>Burwen</surname>
              <given-names>DR</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Association between Guillain-Barr&#233; syndrome and influenza A (H1N1) 2009 monovalent inactivated vaccines in the USA: a meta-analysis</article-title>
          <source> Lancet </source>
          <year>2013</year>
          <volume>381</volume>
          <issue>9876</issue>
          <fpage>1461</fpage>
          <lpage>1468</lpage>
          <issue-id pub-id-type="doi">10.1016/S0140-6736(12)62189-8.</issue-id>
        </element-citation>
      </ref>
      <ref id="B5">
        <label>5</label>
        <mixed-citation>5.Kuntz J, Crane B, Weinmann S, Noleway AL. Myocarditis and pericarditis are rare following live viral vaccinations. Vaccine.2018;36(12):1524-7. DOI:10.1016/j.vaccine.2018.02.030</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Kuntz</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Crane</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Weinmann</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Noleway</surname>
              <given-names>AL</given-names>
            </name>
          </person-group>
          <article-title>Myocarditis and pericarditis are rare following live viral vaccinations</article-title>
          <source> Vaccine </source>
          <year>2018</year>
          <volume>36</volume>
          <issue>12</issue>
          <fpage>1524</fpage>
          <lpage>1527</lpage>
          <issue-id pub-id-type="doi">10.1016/j.vaccine.2018.02.030</issue-id>
        </element-citation>
      </ref>
      <ref id="B6">
        <label>6</label>
        <mixed-citation>6.Caforio A, Pankuweit S, Arbustini E, Basso C, Gimeno-Bhanes J, Felix SB, et al. Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases. Eur Heart J.2013;34(33):2636-48. DOI: <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1093/eurheartj/eht210">https://doi.org/10.1093/eurheartj/eht210</ext-link></mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Caforio</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Pankuweit</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Arbustini</surname>
              <given-names>E</given-names>
            </name>
            <name>
              <surname>Basso</surname>
              <given-names>C</given-names>
            </name>
            <name>
              <surname>Gimeno-Bhanes</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Felix</surname>
              <given-names>SB</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: a position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases</article-title>
          <source> Eur Heart J </source>
          <year>2013</year>
          <volume>34</volume>
          <issue>33</issue>
          <fpage>2636</fpage>
          <lpage>2648</lpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.1093/eurheartj/eht210">https://doi.org/10.1093/eurheartj/eht210</ext-link>
          </comment>
        </element-citation>
      </ref>
      <ref id="B7">
        <label>7</label>
        <mixed-citation>7.Biesbroek S, Beek M, Germans T, Niessen HW, van Rossum AC. Diagnosis of myocarditis: Current state and future perspectives. Int J Cardiol.2015;191:211-9. DOI:10.1016/j.ijcard.2015.05.008</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Biesbroek</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Beek</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Germans</surname>
              <given-names>T</given-names>
            </name>
            <name>
              <surname>Niessen</surname>
              <given-names>HW</given-names>
            </name>
            <name>
              <surname>van Rossum</surname>
              <given-names>AC</given-names>
            </name>
          </person-group>
          <article-title>Diagnosis of myocarditis: Current state and future perspectives</article-title>
          <source> Int J Cardiol </source>
          <year>2015</year>
          <volume>191</volume>
          <fpage>211</fpage>
          <lpage>219</lpage>
          <issue-id pub-id-type="doi">10.1016/j.ijcard.2015.05.008</issue-id>
        </element-citation>
      </ref>
      <ref id="B8">
        <label>8</label>
        <mixed-citation>8.Ferreira VM, Schulz-Menger J, Holmvang G, Kramer CM, Carbone I, Sechtem U, et al. Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations. J Am Coll Cardiol.2018;72(24):3158-76. DOI: 10.1016/j.jacc.2018.09.072</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Ferreira</surname>
              <given-names>VM</given-names>
            </name>
            <name>
              <surname>Schulz-Menger</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Holmvang</surname>
              <given-names>G</given-names>
            </name>
            <name>
              <surname>Kramer</surname>
              <given-names>CM</given-names>
            </name>
            <name>
              <surname>Carbone</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Sechtem</surname>
              <given-names>U</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Cardiovascular Magnetic Resonance in Nonischemic Myocardial Inflammation: Expert Recommendations</article-title>
          <source> J Am Coll Cardiol </source>
          <year>2018</year>
          <volume>72</volume>
          <issue>24</issue>
          <fpage>3158</fpage>
          <lpage>3176</lpage>
          <issue-id pub-id-type="doi">10.1016/j.jacc.2018.09.072</issue-id>
        </element-citation>
      </ref>
      <ref id="B9">
        <label>9</label>
        <mixed-citation>9.Halsell JS, Riddle JR, Atwood JE, Gardner P, Shope R, Poland GA, et al. Myopericarditis Following Smallpox Vaccination Among Vaccinia-Naive US Military Personnel. JAMA. 2003; 289(24):3283&#8211;9. DOI:10.1001/jama.289.24.3283</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Halsell</surname>
              <given-names>JS</given-names>
            </name>
            <name>
              <surname>Riddle</surname>
              <given-names>JR</given-names>
            </name>
            <name>
              <surname>Atwood</surname>
              <given-names>JE</given-names>
            </name>
            <name>
              <surname>Gardner</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Shope</surname>
              <given-names>R</given-names>
            </name>
            <name>
              <surname>Poland</surname>
              <given-names>GA</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Myopericarditis Following Smallpox Vaccination Among Vaccinia-Naive US Military Personnel</article-title>
          <source> JAMA </source>
          <year>2003</year>
          <volume>289</volume>
          <issue>24</issue>
          <fpage>3283</fpage>
          <lpage>3289</lpage>
          <issue-id pub-id-type="doi">10.1001/jama.289.24.3283</issue-id>
        </element-citation>
      </ref>
      <ref id="B10">
        <label>10</label>
        <mixed-citation>10.Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. C4591001 Clinical Trial Group. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med. 2020;383(27):2603&#8211;15. DOI: 10.1056/NEJMoa2034577</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Polack</surname>
              <given-names>FP</given-names>
            </name>
            <name>
              <surname>Thomas</surname>
              <given-names>SJ</given-names>
            </name>
            <name>
              <surname>Kitchin</surname>
              <given-names>N</given-names>
            </name>
            <name>
              <surname>Absalon</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Gurtman</surname>
              <given-names>A</given-names>
            </name>
            <name>
              <surname>Lockhart</surname>
              <given-names>S</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>C4591001 Clinical Trial Group. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine</article-title>
          <source> N Engl J Med </source>
          <year>2020</year>
          <volume>383</volume>
          <issue>27</issue>
          <fpage>2603</fpage>
          <lpage>2615</lpage>
          <issue-id pub-id-type="doi">10.1056/NEJMoa2034577</issue-id>
        </element-citation>
      </ref>
      <ref id="B11">
        <label>11</label>
        <mixed-citation>11.Oliver S, Gargano J, Marin M, Wallace M, Curron KG, Chamberland M, et al. The Advisory Committee on Immunization Practices&#8217; Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine &#8212; United States, December 2020. MMWR Morb Mortal Wkly Rep.2020;69(50):1922-4. DOI: <ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.15585/mmwr.mm6950e2">http://dx.doi.org/10.15585/mmwr.mm6950e2</ext-link></mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Oliver</surname>
              <given-names>S</given-names>
            </name>
            <name>
              <surname>Gargano</surname>
              <given-names>J</given-names>
            </name>
            <name>
              <surname>Marin</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Wallace</surname>
              <given-names>M</given-names>
            </name>
            <name>
              <surname>Curron</surname>
              <given-names>KG</given-names>
            </name>
            <name>
              <surname>Chamberland</surname>
              <given-names>M</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>The Advisory Committee on Immunization Practices&#8217; Interim Recommendation for Use of Pfizer-BioNTech COVID-19 Vaccine &#8212; United States, December 2020</article-title>
          <source> MMWR Morb Mortal Wkly Rep </source>
          <year>2020</year>
          <volume>69</volume>
          <issue>50</issue>
          <fpage>1922</fpage>
          <lpage>1924</lpage>
          <ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.15585/mmwr.mm6950e2">http://dx.doi.org/10.15585/mmwr.mm6950e2</ext-link>
        </element-citation>
      </ref>
      <ref id="B12">
        <label>12</label>
        <mixed-citation>12.Kim HW, Jenista ER, Wendell DC, Azevedo CF, Campbell MJ, Darty SN, et al. Patients With Acute Myocarditis Following mRNA COVID-19 Vaccination. JAMA Cardiol. 2021;6(10):1196-201. Doi:10.1001/jamacardio.2021.2828</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Kim</surname>
              <given-names>HW</given-names>
            </name>
            <name>
              <surname>Jenista</surname>
              <given-names>ER</given-names>
            </name>
            <name>
              <surname>Wendell</surname>
              <given-names>DC</given-names>
            </name>
            <name>
              <surname>Azevedo</surname>
              <given-names>CF</given-names>
            </name>
            <name>
              <surname>Campbell</surname>
              <given-names>MJ</given-names>
            </name>
            <name>
              <surname>Darty</surname>
              <given-names>SN</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Patients With Acute Myocarditis Following mRNA COVID-19 Vaccination</article-title>
          <source> JAMA Cardiol </source>
          <year>2021</year>
          <volume>6</volume>
          <issue>10</issue>
          <fpage>1196</fpage>
          <lpage>1201</lpage>
          <issue-id pub-id-type="doi">10.1001/jamacardio.2021.2828</issue-id>
        </element-citation>
      </ref>
      <ref id="B13">
        <label>13</label>
        <mixed-citation>13.Bozkurt B, Kamat I, Hotez PJ. Myocarditis With COVID-19 mRNA Vaccines. Circulation.2021;144(6):471-84. DOI:10.1161/CIRCULATIONAHA.121.056135</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Bozkurt</surname>
              <given-names>B</given-names>
            </name>
            <name>
              <surname>Kamat</surname>
              <given-names>I</given-names>
            </name>
            <name>
              <surname>Hotez</surname>
              <given-names>PJ</given-names>
            </name>
          </person-group>
          <article-title>Myocarditis With COVID-19 mRNA Vaccines</article-title>
          <source> Circulation </source>
          <year>2021</year>
          <volume>144</volume>
          <issue>6</issue>
          <fpage>471</fpage>
          <lpage>484</lpage>
          <issue-id pub-id-type="doi">10.1161/CIRCULATIONAHA.121.056135</issue-id>
        </element-citation>
      </ref>
      <ref id="B14">
        <label>14</label>
        <mixed-citation>14.Cimaglia P, Tolomeo P, Rapezzi C. Acute Myocarditis after SARS-CoV-2 Vaccination in a 24-Year-Old Man. Rev Port Cardiol. 2021[ahead print]. DOI:10.1016/j.repc.2021.07.005</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Cimaglia</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Tolomeo</surname>
              <given-names>P</given-names>
            </name>
            <name>
              <surname>Rapezzi</surname>
              <given-names>C</given-names>
            </name>
          </person-group>
          <article-title>Acute Myocarditis after SARS-CoV-2 Vaccination in a 24-Year-Old Man</article-title>
          <source> Rev Port Cardiol </source>
          <year>2021</year>
          <comment>ahead print</comment>
          <issue-id pub-id-type="doi">10.1016/j.repc.2021.07.005</issue-id>
        </element-citation>
      </ref>
      <ref id="B15">
        <label>15</label>
        <mixed-citation>15.Segal Y, Shoenfeld Y. Vaccine-induced autoimmunity: the role of molecular mimicry and immune crossreaction. Cell Mol Immunol. 2018;15(6):586-94. DOI: 10.1038/cmi.2017.151.</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Segal</surname>
              <given-names>Y</given-names>
            </name>
            <name>
              <surname>Shoenfeld</surname>
              <given-names>Y</given-names>
            </name>
          </person-group>
          <article-title>Vaccine-induced autoimmunity: the role of molecular mimicry and immune crossreaction</article-title>
          <source> Cell Mol Immunol </source>
          <year>2018</year>
          <volume>15</volume>
          <issue>6</issue>
          <fpage>586</fpage>
          <lpage>594</lpage>
          <issue-id pub-id-type="doi">10.1038/cmi.2017.151.</issue-id>
        </element-citation>
      </ref>
      <ref id="B16">
        <label>16</label>
        <mixed-citation>16.Rosenblum HG, Hadler SC, Moulia D, Shimabukuro TT, Su JR, Tepper NK, et al. Use of COVID-19 Vaccines After Reports of Adverse Events Among Adult Recipients of Janssen (Johnson &amp; Johnson) and mRNA COVID-19 Vaccines (Pfizer-BioNTech and Moderna): Update from the Advisory Committee on Immunization Practices - United States, July 2021. MMWR Morb Mortal Wkly Rep. 2021;70(32):1094-9. DOI:10.15585/mmwr.mm7032e4</mixed-citation>
        <element-citation publication-type="journal">
          <person-group person-group-type="author">
            <name>
              <surname>Rosenblum</surname>
              <given-names>HG</given-names>
            </name>
            <name>
              <surname>Hadler</surname>
              <given-names>SC</given-names>
            </name>
            <name>
              <surname>Moulia</surname>
              <given-names>D</given-names>
            </name>
            <name>
              <surname>Shimabukuro</surname>
              <given-names>TT</given-names>
            </name>
            <name>
              <surname>Su</surname>
              <given-names>JR</given-names>
            </name>
            <name>
              <surname>Tepper</surname>
              <given-names>NK</given-names>
            </name>
            <etal>et al</etal>
          </person-group>
          <article-title>Use of COVID-19 Vaccines After Reports of Adverse Events Among Adult Recipients of Janssen (Johnson &amp; Johnson) and mRNA COVID-19 Vaccines (Pfizer-BioNTech and Moderna): Update from the Advisory Committee on Immunization Practices - United States, July 2021</article-title>
          <source> MMWR Morb Mortal Wkly Rep </source>
          <year>2021</year>
          <volume>70</volume>
          <issue>32</issue>
          <fpage>1094</fpage>
          <lpage>1099</lpage>
          <pub-id pub-id-type="doi">10.15585/mmwr.mm7032e4</pub-id>
        </element-citation>
      </ref>
    </ref-list>
    <fn-group>
      <fn fn-type="other">
        <p>Vincula&#231;&#227;o acad&#234;mica</p>
        <p>N&#227;o h&#225; vincula&#231;&#227;o deste estudo a programas de p&#243;s-gradua&#231;&#227;o.</p>
        <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 fn-type="supported-by">
        <p><bold>Fontes de financiamento:</bold> 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>Research Letter</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Acute Myocarditis Following mRNA COVID-19 Vaccine</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-6894-648X</contrib-id>
          <name>
            <surname>Gomes</surname>
            <given-names>Daniel A.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-0881-053X</contrib-id>
          <name>
            <surname>Santos</surname>
            <given-names>Rita R.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Freitas</surname>
            <given-names>Pedro</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Paiva</surname>
            <given-names>Mariana S.</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-5592-6199</contrib-id>
          <name>
            <surname>Ferreira</surname>
            <given-names>Jorge</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-1625-1459</contrib-id>
          <name>
            <surname>Trabulo</surname>
            <given-names>Marisa</given-names>
          </name>
          <xref ref-type="aff" rid="aff1001">
            <sup>1</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1001">
        <label>1</label>
        <country country="PT">Portugal</country>
        <institution content-type="original">Departamento de Cardiologia, Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental, Carnaxide &#8211; Portugal</institution>
      </aff>
      <author-notes>
        <corresp id="c01001">Mailing Address: Daniel A. Gomes &#8226; Cardiology Department &#8211; Hospital de Santa Cruz, Centro Hospitalar de Lisboa Ocidental &#8211; 2790-134. Carnaxide &#8211; Portugal E-mail: dgomes@chlo.min-saude.pt</corresp>
        <fn fn-type="con">
          <p>Author Contributions</p>
          <p>Conception and design of the research: Gomes DA, Ferreira J, Trabulo M; Acquisition of data: Gomes DA, Santos RR, Freitas P, Paiva MS; Analysis and interpretation of the data and Critical revision of the manuscript for intellectual content: Gomes DA, Santos RR, Freitas P, Paiva MS, Ferreira J, Trabulo M; Writing of the manuscript: Gomes DA.</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>
      <kwd-group xml:lang="en">
        <kwd>Coronavirus-19</kwd>
        <kwd>COVID-19</kwd>
        <kwd>Vaccine/adverse effects</kwd>
        <kwd>Immunogenicity Vaccine</kwd>
        <kwd>Molecular Mimicry</kwd>
        <kwd>Myocarditis</kwd>
        <kwd>Diagnostic Imaging</kwd>
      </kwd-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introduction</title>
        <p>Vaccination is one of the most important breakthroughs of modern medicine and constitute a major advance in the prevention of infectious diseases.<sup><xref rid="B1" ref-type="bibr">1</xref></sup>Overall, vaccines are effective and have an excellent general safety profile.<sup><xref rid="B2" ref-type="bibr">2</xref></sup>In fact, reports of severe adverse effects following vaccination are extremely rare and idiosyncratic.<sup><xref rid="B2" ref-type="bibr">2</xref></sup></p>
        <p>As the vaccine&#8217;s mechanism of action is based on the host immune response, a close relationship with autoimmunity cannot be disregarded.<sup><xref rid="B3" ref-type="bibr">3</xref></sup>Cases of immunologic reactogenicity, such as Guillain-Barr&#233; syndrome and acute myocarditis following vaccination have been previously reported.<sup><xref rid="B4" ref-type="bibr">4</xref>, <xref rid="B5" ref-type="bibr">5</xref></sup></p>
        <p>We report the case of a young male patient who developed acute myocarditis following the mRNA vaccine against SARS-CoV-2.</p>
      </sec>
      <sec>
        <title>Case report</title>
        <p>A 32-year-old male individual was admitted with presyncope and oppressive retrosternal chest pain. The pain lasted for two hours, did not radiate and was not modified by respiratory movements or position. He had had fever (39&#186;C) and generalized myalgia for two days, starting one day after the administration of the second dose of the mRNA COVID-19 vaccine. The patient was hemodynamically stable and his physical examination at admission was unremarkable, except for the presence of fever. He denied any recent episodes of chest pain, respiratory tract or gastrointestinal infection. He was not taking any drugs or medications and no occupational or recreational risk factors were identified.</p>
        <p>The patient was otherwise healthy except for a history of idiopathic myopericarditis, which occurred 13 years before. At that time, the cardiac magnetic resonance (CMR) assessment performed in the acute phase revealed subepicardial late gadolinium enhancement in the lateral wall. The patient was discharged and remained stable, under regular clinical follow-up. Complete resolution of these findings was observed in a CMR at one year of follow-up.</p>
        <p>Given the characteristics of the chest pain in a young patient with a concomitant viral syndrome, myocarditis was considered as a likely diagnosis. The patient had elevated inflammatory parameters (leukocytosis and C-reactive protein 4.6mg/dL) and myocardial biomarkers (high-sensitive cardiac troponin T 834ng/L and NT-proBNP 433pg/mL) on blood analysis. The chest radiography was normal. The ECG showed diffuse concave ST-segment elevation ( <xref rid="f01001" ref-type="fig">figure 1A</xref> ). On transthoracic echocardiography, left ventricular ejection fraction was preserved (58%) and no abnormalities were observed in segmental contractility, although the global longitudinal strain was mildly reduced (-17%). There was no pericardial effusion. The CMR revealed subepicardial late gadolinium enhancement in the mid anterior, lateral and inferior walls ( <xref rid="f02001" ref-type="fig">figure 2A</xref> ) accompanied by increased native T1 and T2 in the mid anterior and lateral segments ( <xref rid="f02001" ref-type="fig">figures 2B</xref> and <xref rid="f02001" ref-type="fig">2C</xref> ). No inflammation signs were observed in the pericardium. Naso- and oropharyngeal swab polymerase chain reaction (PCR) tests for SARS-CoV-2 were negative on two different occasions. Given the high clinical suspicion and a CMR pattern consistent with acute myocarditis in a patient without any known cardiovascular risk factors, coronary angiography was not performed.</p>
        <p>
          <fig id="f01001">
            <label>Figure 1</label>
            <caption>
              <title>&#8211; ECG at admission demonstrating diffuse concave ST-segment elevation (figure 1A) and ECG at three months of follow-up showing resolution of ST-segment abnormalities (figure 1B).</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-118-04-0783-10469-gf01-en.tif"/></fig>
        </p>
        <p>
          <fig id="f02001">
            <label>Figure 2</label>
            <caption>
              <title>&#8211; Cardiac magnetic resonance (CMR) at admission demonstrating subepicardial late gadolinium enhancement (LGE) in the mid anterior, lateral and inferior walls (figure 2A), and increased native T1 (figure 2B) and T2 (figure 2C). The CMR at three months of follow-up revealed improvement in the subepicardial late gadolinium enhancement pattern (figure 2D), and normalization of native T1 (figure 2E) and T2 (figure 2F).</title>
            </caption>
            <graphic xlink:href="1678-4170-abc-118-04-0783-10469-gf02-en.tif"/></fig>
        </p>
        <p>The diagnosis of acute myocarditis was assumed. The patient was discharged three days after admission and advised against intense physical activity during a three to six-month period. An ECG was repeated after clinical improvement and revealed normalization of the ST-segment elevation ( <xref rid="f01001" ref-type="fig">figure 1B</xref> ). A CMR assessment at three months of follow-up demonstrated significant improvement in the subepicardial late gadolinium enhance pattern ( <xref rid="f02001" ref-type="fig">figure 2D</xref> ) and normalization of the previously observed abnormalities in mapping T1 and T2 sequences ( <xref rid="f02001" ref-type="fig">figures 2E</xref> and <xref rid="f02001" ref-type="fig">2F</xref> ).</p>
      </sec>
      <sec sec-type="discussion">
        <title>Discussion</title>
        <p>Myocarditis is an inflammatory disease of the myocardium caused by a variety of infectious and non-infectious conditions.6 Its clinical presentation varies widely, ranging from mild chest pain to cardiogenic shock or life-threatening ventricular arrhythmias.<sup><xref rid="B6" ref-type="bibr">6</xref>, <xref rid="B7" ref-type="bibr">7</xref></sup>Although the cardiac biopsy remains the gold standard, it is not routinely performed in clinical practice for most patients and, therefore, the CMR, by meeting the modified Lake Louise Criteria, is extremely useful in establishing the diagnosis.<sup><xref rid="B6" ref-type="bibr">6</xref> - <xref rid="B8" ref-type="bibr">8</xref> </sup></p>
        <p>There are only a few reports of myocarditis following vaccination. Although there were some initial concerns about the development of inflammatory cardiac disease in live viral vaccine recipients, more recent studies suggest its overall risk is not increased.<sup><xref rid="B5" ref-type="bibr">5</xref>, <xref rid="B9" ref-type="bibr">9</xref></sup>In fact, in a cohort including over 41000 patients, only one case of definitive pericarditis and none of myocarditis were diagnosed in the first 42 days after vaccination.<sup><xref rid="B5" ref-type="bibr">5</xref></sup></p>
        <p>The introduction of vaccines against SARS-CoV-2 is a key element in controlling the spread of this pandemic. Among those receiving mRNA COVID-19 vaccine in large-scale clinical trials, it proved to be highly effective and safe, with no reports of significant adverse cardiovascular effects.<sup><xref rid="B10" ref-type="bibr">10</xref></sup>Systemic symptoms related to immunologic reactogenicity were common, mostly mild to moderate ones, and more frequently observed following the second</p>
        <p>dose, with a median onset of 1-2 days after vaccine application.<sup><xref rid="B11" ref-type="bibr">11</xref></sup></p>
        <p>We report a case of a 32-year-old man who developed self-limited acute myocarditis after COVID-19 immunization. This clinical case is in line with recently published ones.<sup><xref rid="B12" ref-type="bibr">12</xref> - <xref rid="B14" ref-type="bibr">14</xref> </sup>As we described, acute myocarditis following COVID-19 vaccination appears to be a potentially rare and self-limited complication, affecting mostly young and healthy male patients two to three days after receiving the second dose.</p>
        <p>The exact immunological mechanisms linking the vaccine to the development of acute myocarditis is not completely clear. Autoinflammatory syndrome, cross-reactivity, molecular mimicry, and autoantibody generation in susceptible or predisposed individuals have been suggested to be implicated in pathogenesis.<sup><xref rid="B13" ref-type="bibr">13</xref></sup>In fact, previous reports have elicited the role of cross-reaction and mimicry in post vaccination autoimmune phenomena.<sup><xref rid="B15" ref-type="bibr">15</xref></sup></p>
        <p>Although other etiologies such as viral myocarditis coincidental with the vaccination timing cannot be definitively excluded, given the temporal association, we can hypothesize that the immune response to the vaccine may have triggered the recurrence of myocarditis in this patient.</p>
        <p>More studies are needed to further clarify the epidemiology, pathophysiology, and long-term clinical outcomes of these patients. Future research on this subject should focus on: (1) exploring predisposing factors and pathophysiological mechanisms for the development of myocardial injury following COVID-19 vaccination (including molecular mimicry, autoantibody formation, and the role of specific immune cell populations); (2) characterizing myocardial ultrastructural and functional changes, as well as cardiac biomarkers and cardiac function; (3) prospectively characterizing these patients&#8217; clinical presentation, clinical course and long-term outcomes.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclusions</title>
        <p>Self-limited acute myocarditis may be a potential and rare adverse effect of mRNA COVID-19 vaccines. While clinicians must be aware of this possibility, by no means it should discourage vaccination, as the risk-benefit analysis regarding COVID-19 immunization shows a consistent beneficial effect across all groups.<sup><xref rid="B14" ref-type="bibr">14</xref>, <xref rid="B16" ref-type="bibr">16</xref></sup>The vaccine is currently recommended for everyone aged &#8805; 12 years.<sup><xref rid="B16" ref-type="bibr">16</xref></sup></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>
          <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 fn-type="supported-by">
          <p><bold>Sources of Funding:</bold> There were no external funding sources for this study.</p>
        </fn>
      </fn-group>
    </back>
  </sub-article>
</article>
