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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">ijcs</journal-id>
      <journal-title-group>
        <journal-title>International Journal of Cardiovascular Sciences</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Int J Cardiovasc Sci</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">2359-4802</issn>
      <issn pub-type="epub">2359-5647</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id specific-use="scielo-v3" pub-id-type="publisher-id">GZwv5yQtCpTDpwz46FbBD7q</article-id>
      <article-id specific-use="scielo-v2" pub-id-type="publisher-id">S2359-56472023000100211</article-id>
      <article-id pub-id-type="other">00211</article-id>
      <article-id pub-id-type="doi">10.36660/ijcs.20220035</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>ORIGINAL ARTICLE</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Covid-19 and Heart Involvement: A Systematic Review of Literature</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-0623-8135</contrib-id>
          <name>
            <surname>Moraes</surname>
            <given-names>Francisco Cezar Aquino de</given-names>
          </name>
          <role>Conception and design of the research, acquisition of data, analysis and interpretation of the data, statistical analysis and writing of the manuscript</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Santos</surname>
            <given-names>Rafael Reis do Esp&#237;rito</given-names>
          </name>
          <role>acquisition of data, analysis and interpretation of the data, statistical analysis and writing of the manuscript</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-8547-6942</contrib-id>
          <name>
            <surname>Moraes</surname>
            <given-names>Joel Campos de</given-names>
          </name>
          <role>acquisition of data, analysis and interpretation of the data, statistical analysis and writing of the manuscript</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Mota</surname>
            <given-names>Aline Carolina Castro</given-names>
          </name>
          <role>acquisition of data, analysis and interpretation of the data, statistical analysis and writing of the manuscript</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-1215-8804</contrib-id>
          <name>
            <surname>Pessoa</surname>
            <given-names>Fernando Rocha</given-names>
          </name>
          <role>acquisition of data, analysis and interpretation of the data, statistical analysis and writing of the manuscript</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-4863-6879</contrib-id>
          <name>
            <surname>Sarges</surname>
            <given-names>Dayanne Coutinho</given-names>
          </name>
          <role>acquisition of data, analysis and interpretation of the data, statistical analysis and writing of the manuscript</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Moraes</surname>
            <given-names>Davi Alexandrino</given-names>
          </name>
          <role>acquisition of data, analysis and interpretation of the data, statistical analysis and writing of the manuscript</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
        </contrib>
        <contrib contrib-type="author">
          <name>
            <surname>Souza</surname>
            <given-names>Dilma do Socorro Moraes de</given-names>
          </name>
          <role>Conception and design of the research, critical revision of the manuscript for intellectual content</role>
          <xref ref-type="aff" rid="aff1">
            <sup>1</sup>
          </xref>
          <xref ref-type="aff" rid="aff2">
            <sup>2</sup>
          </xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label> 1 </label>
        <institution content-type="orgname">Universidade Federal do Par&#225;</institution>
        <addr-line>
          <named-content content-type="city">Bel&#233;m</named-content>
          <named-content content-type="state">PA</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original"> Universidade Federal do Par&#225; , Bel&#233;m , PA &#8211; Brazil </institution>
      </aff>
      <aff id="aff2">
        <label> 2 </label>
        <institution content-type="orgname">Funda&#231;&#227;o Hospital de Cl&#237;nicas Gaspar Vianna</institution>
        <addr-line>
          <named-content content-type="city">Bel&#233;m</named-content>
          <named-content content-type="state">PA</named-content>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original"> Funda&#231;&#227;o Hospital de Cl&#237;nicas Gaspar Vianna , Bel&#233;m , PA &#8211; Brazil </institution>
      </aff>
      <author-notes>
        <corresp id="c01">Mailing Address: Dilma do Socorro Moraes de Souza Universidade Federal do Par&#225;. Rua Augusto Corr&#234;a, 01. Postal code: 66075-110. Guam&#225;, Bel&#233;m, PA &#8211; Brazil. E-mail: <email>dsouza@cardiol.br</email> </corresp>
        <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>
      <pub-date date-type="pub" publication-format="electronic">
        <day>03</day>
        <month>03</month>
        <year>2023</year>
      </pub-date>
      <pub-date date-type="collection" publication-format="electronic">
        <year>2023</year>
      </pub-date>
      <volume>36</volume>
      <elocation-id>e20220035</elocation-id>
      <history>
        <date date-type="received">
          <day>3</day>
          <month>03</month>
          <year>2022</year>
        </date>
        <date date-type="rev-recd">
          <day>8</day>
          <month>09</month>
          <year>2022</year>
        </date>
        <date date-type="accepted">
          <day>16</day>
          <month>10</month>
          <year>2022</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>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background</title>
          <p>Recent reports in the literature have indicated that infection by coronavirus disease 2019 (COVID-19) causes cardiac complications, such as heart failure, arrhythmia, myocardial infarction, and even fulminant myocarditis. These complications have been identified as the cause of death in some patients infected with SARS-CoV-2.</p>
        </sec>
        <sec>
          <title>Objectives</title>
          <p>To analyze echocardiographic and electrocardiographic changes, treatments used, and clinical outcomes in patients with myocarditis and COVID-19.</p>
        </sec>
        <sec>
          <title>Methods</title>
          <p>The items described for Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were followed. This review included articles in English, Portuguese, and Spanish that reported cardiac involvement, injury, or myocardial inflammation in patients who acquired COVID-19 (SARS-CoV-2).</p>
        </sec>
        <sec>
          <title>Results</title>
          <p>Five databases were consulted to find 1,726 articles. After applying the eligibility criteria, a total of 22 studies were considered qualified. ST-segment (section of the electrocardiogram corresponding the end of the S wave to the beginning of the T wave) elevation and tachyarrhythmia were the most common changes found in the electrocardiographic analysis of patients affected with COVID-19. Concerning echocardiography, there was a high frequency of decreased ejection fraction and occurrence of pericardial effusion.</p>
        </sec>
        <sec>
          <title>Conclusion</title>
          <p>This systematic review provides a potential tool for the analysis of cardiac changes and implications caused in patients affected by SARS-CoV-2 infection, with emphasis on the presence of tachyarrhythmia on electrocardiogram (ECG) and decreased ejection fraction on echocardiogram.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <kwd>COVID-19</kwd>
        <kwd>Myocarditis</kwd>
        <kwd>Systematic Review</kwd>
      </kwd-group>
      <counts>
        <fig-count count="1"/>
        <table-count count="3"/>
        <equation-count count="0"/>
        <ref-count count="73"/>
      </counts>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>At the end of December 2019, Chinese health authorities reported a sudden increase in cases of pneumonia that were epidemiologically linked to a market for seafood and wet animals located in Wuhan, Hubei Province, China. The causative agent of viral origin was isolated and identified as a new coronavirus strain, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). <sup><xref ref-type="bibr" rid="B1">1</xref> , <xref ref-type="bibr" rid="B2">2</xref></sup></p>
      <p>Coronavirus disease 2019 (COVID-19) has mainly respiratory manifestations, with clinical symptoms of cough, fever, progressive shortness of breath, and complications resulting from pneumonia and acute respiratory distress syndrome. As cases increased, cardiovascular manifestations and complications were reported. <sup><xref ref-type="bibr" rid="B3">3</xref> - <xref ref-type="bibr" rid="B5">5</xref></sup></p>
      <p>The infection occurs in humans through contact with respiratory secretions. The entry of SARS-CoV-2 into the human body is through angiotensin-converting enzyme 2 (ACE2). ACE2 is highly expressed in cell membranes of lungs, heart, intestine, blood vessels, and others, and it becomes a mediating receptor of SARS-CoV-2 entry into the cell membrane. The virus has a more compact structure with greater binding stability and a high affinity for ACE2. ACE2 is also responsible for acting in the modulation of the renin-angiotensin-aldosterone system, which is important for regulating blood pressure and other functions related to the cardiovascular and renal systems. <sup><xref ref-type="bibr" rid="B6">6</xref> , <xref ref-type="bibr" rid="B7">7</xref></sup></p>
      <p>COVID-19 can cause myocarditis, which leads to serious damage to the cardiovascular health of patients with coronary artery disease. The main mechanisms involved in the pathogenesis are the hyperinflammatory state mediated by pro-inflammatory cytokines such as the interleukins IL-2, IL-10, IL-6, IL-8 and tumor necrosis factor (TNF-&#945;); endothelial dysfunction resulting from the interaction between ACE2 and SARS-CoV-2; processes of macro- and microthrombotic arterial occlusion induced by stress in the autonomic nervous system; and endothelial, coronary, and smooth muscle cell dysfunction associated with macrophages and platelet activation, precipitating instability and rupture of the atheromatous plaque that leads to thrombus formation. These factors together lead to myocardial injury, hypoxia, and cardiotoxicity, which cause myocarditis and aggravation in patients with preexisting coronary artery disease. <sup><xref ref-type="bibr" rid="B6">6</xref> - <xref ref-type="bibr" rid="B9">9</xref></sup></p>
      <p>Viral infection is described as one of the most common infectious causes of myocarditis onset, particularly influenza and parvovirus B19. However, cardiac involvement as a complication of SARS-CoV-2 infection is still poorly understood. It appears that it affects the cardiovascular system because of an elevation of cardiac biomarkers such as troponin T and type B natriuretic peptide. <sup><xref ref-type="bibr" rid="B10">10</xref> , <xref ref-type="bibr" rid="B11">11</xref></sup></p>
      <p>Cardiac dysfunction does not present as a common sequela in patients affected by SARS-CoV-2; however, a significant number of patients were observed with myocardial injury. COVID-19 infection can cause cardiac complications, such as heart failure, arrhythmia, myocardial infarction, and even fulminant myocarditis. The literature also reports the occurrence of acute myopericarditis and pericardial effusion in patients with COVID-19, even in the absence of severe pulmonary disease. Myocarditis has already been identified as the cause of death in some patients infected with SARS-CoV-2. The highest frequency of cardiac involvement is in the focal myocardium, with risk of arrhythmia, progression to fulminant heart failure, and cardiogenic shock. <sup><xref ref-type="bibr" rid="B3">3</xref> , <xref ref-type="bibr" rid="B12">12</xref> - <xref ref-type="bibr" rid="B14">14</xref></sup></p>
      <p>The objective of this systematic review is to map the clinical changes in electrocardiogram (ECG) and echocardiogram of patients with COVID-19 confirmed by reverse-transcriptase chain reaction (RT-PCR), who developed myocarditis, as well as the clinical outcomes and treatments employed in each case.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <sec>
        <title>Protocol and Registration</title>
        <p>This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), which consists of a checklist with 27 items and a four-step flowchart to assist the construction of systematic reviews and meta-analyses. <sup><xref ref-type="bibr" rid="B15">15</xref></sup></p>
      </sec>
      <sec>
        <title>Eligibility Criteria</title>
        <sec>
          <title>Inclusion Criteria</title>
          <p>Only case reports and case series that recorded cardiac involvement, injury, or myocardial inflammation in patients who acquired COVID-19 confirmed by RT-PCR were chosen for this study. The articles were in English, Portuguese, and Spanish, and only studies that presented information on clinical manifestations, with or without changes in the ECG and echocardiogram were included. Alterations considered abnormal in the ECG were based on the Recommendations for the Standardization and Interpretation of the Electrocardiogram Guidelines from the American Heart Association/American College of Cardiology/Heart Rhythm Society, consisting of atrial or ventricular arrhythmias, conduction disorders, or other electrophysiological information indicated in the exam as suggestive of pathology. Abnormalities in echocardiogram followed recommendations from the American Society of Echocardiography and included reduced ejection fraction, motility disorders, wall or ventricle thickening, presence of blood clots, or other morphological and non-morphological changes that imply abnormal heart functioning. <sup><xref ref-type="bibr" rid="B16">16</xref> - <xref ref-type="bibr" rid="B22">22</xref></sup></p>
        </sec>
        <sec>
          <title>Exclusion Criteria</title>
          <p>In this study, articles that were not case reports, series of cases, or observational studies were excluded. Articles from literature reviews, encyclopedias, editorials, book chapters, conference summaries, correspondence, reviews, news, and small communications were also excluded. Studies that did not present data regarding age, sex, ECG, echocardiogram, RT-PCR result, and myocarditis related to SARS-CoV-2 infection were excluded.</p>
        </sec>
      </sec>
    </sec>
    <sec>
      <title>Information Sources and Search Strategies</title>
      <p>The literature review used databases in which all studies reporting infection-induced myocarditis due to COVID-19 were described. The following descriptors were used: &#8220;coronavirus&#8221;, &#8220;COVID-19&#8221;, &#8220;myocarditis&#8221;, &#8220;myopericarditis&#8221;, &#8220;case report&#8221;, and &#8220;coronavirus infections&#8221;.</p>
      <p>The articles used are indexed in the Medical Literature Analysis and Retrieval System Online (Medline) databases, consulted in PubMed, Scientific Electronic Library Online (SciELO), Cochrane CENTRAL, LILACS, and Science Direct.</p>
    </sec>
    <sec>
      <title>Study Selection</title>
      <p>The screening of the articles included in this work was performed based on the analysis of whether the title and abstract met the eligibility criteria, which were elected by fulfilling the inclusion criteria and not meeting any of the exclusion criteria. Articles that met the inclusion criteria were read in full, while the articles that met any of the exclusion criteria were excluded from the selection of this review.</p>
    </sec>
    <sec>
      <title>Data Collection Process and Data Items</title>
      <p>Among the articles included, the authors' names, year, place of publication, and methodology were removed. For case reports, information on age, sex, and possible complaints presented by the patient during the admission period were removed. Diagnostic strategies, laboratory tests performed, treatment, outcomes, and complications were extracted.</p>
    </sec>
    <sec>
      <title>Synthesis of Results and Summary of Measures</title>
      <p>For the analysis of the results obtained, the data were tabulated and duly described regarding their absolute frequency and relative frequency.</p>
    </sec>
    <sec>
      <title>Risk of Bias of the Included Studies</title>
      <p>To reduce the risk of bias, all studies included in this work underwent peer review.</p>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <sec>
        <title>Study Selection</title>
        <p>Five databases were consulted to find 1,726 articles, and, of these, 266 duplicated articles were excluded from more than one database, resulting in 1,075 articles. In addition, 363 articles were not included in the analysis because of the non-association between COVID-19 and myocarditis. Thus, out of a total of 1,726 articles, 22 were selected, according to the eligibility criteria for the study, which represents 0.01% of all the articles found ( <xref ref-type="fig" rid="f01">Figure 1</xref> ).</p>
        <p>
          <fig id="f01">
            <label>Figure 1</label>
            <caption>
              <title>&#8211; Diagram of the research selection flow adapted from the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA).</title>
            </caption>
            <graphic xlink:href="2359-5647-ijcs-36-e20220035-20035-gf01.tif"/></fig>
        </p>
      </sec>
      <sec>
        <title>Study Characteristics</title>
        <p>Of the 22 articles selected, 21 were case report studies <sup><xref ref-type="bibr" rid="B23">23</xref> - <xref ref-type="bibr" rid="B44">44</xref></sup> and 1 was a case series study. <sup><xref ref-type="bibr" rid="B27">27</xref></sup> Therefore, the number of participants in the studies ranged from 1 to 2 patients. Of the articles, 17 were published in 2020 <sup><xref ref-type="bibr" rid="B23">23</xref> , <xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B26">26</xref> , <xref ref-type="bibr" rid="B28">28</xref> , <xref ref-type="bibr" rid="B29">29</xref> , <xref ref-type="bibr" rid="B31">31</xref> - <xref ref-type="bibr" rid="B34">34</xref> , <xref ref-type="bibr" rid="B36">36</xref> - <xref ref-type="bibr" rid="B44">44</xref></sup> and 5 in 2021. <sup><xref ref-type="bibr" rid="B24">24</xref> , <xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B29">29</xref> , <xref ref-type="bibr" rid="B30">30</xref> , <xref ref-type="bibr" rid="B35">35</xref></sup> All articles were peer-reviewed. Ten studies were conducted in the United States of America. <sup><xref ref-type="bibr" rid="B27">27</xref> - <xref ref-type="bibr" rid="B30">30</xref> , <xref ref-type="bibr" rid="B32">32</xref> , <xref ref-type="bibr" rid="B33">33</xref> , <xref ref-type="bibr" rid="B37">37</xref> - <xref ref-type="bibr" rid="B40">40</xref></sup> Six studies were conducted in Europe: three in France, <sup><xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B34">34</xref> , <xref ref-type="bibr" rid="B42">42</xref></sup> two in Spain, <sup><xref ref-type="bibr" rid="B36">36</xref> , <xref ref-type="bibr" rid="B41">41</xref></sup> and one in Italy. <sup><xref ref-type="bibr" rid="B31">31</xref></sup> In the Asian continent, three studies were conducted: two in Iran <sup><xref ref-type="bibr" rid="B24">24</xref> , <xref ref-type="bibr" rid="B26">26</xref></sup> and one in the United Arab Emirates. <sup><xref ref-type="bibr" rid="B23">23</xref></sup> In the African continent, one study was conducted in Morocco. <sup><xref ref-type="bibr" rid="B35">35</xref></sup> In South America, two studies were conducted: one in Brazil, <sup><xref ref-type="bibr" rid="B43">43</xref></sup> and one in Colombia. <sup><xref ref-type="bibr" rid="B44">44</xref></sup></p>
      </sec>
      <sec>
        <title>Risk of Bias within the Studies</title>
        <p>Descriptive studies, such as case reports and case series are subject to bias, due to their format, methods, and level of evidence.</p>
      </sec>
      <sec>
        <title>Results of Individual Studies</title>
        <p>Twenty-two case reports were selected for the systematic review. Al-Assaf et al. <sup><xref ref-type="bibr" rid="B23">23</xref></sup> described an atypical presentation of COVID-19 as subclinical myocarditis with persistent high-degree atrioventricular block treated with pacemaker implant, in a 58-year-old man in the United Arab Emirates. Nikoo et al. <sup><xref ref-type="bibr" rid="B24">24</xref></sup> presented a case of systolic dysfunction and complete heart block as complications of fulminant myocarditis in a case of recovered COVID-19 in a 38-year-old woman from Iran. Fischer et al. <sup><xref ref-type="bibr" rid="B25">25</xref></sup> described a case report of isolated myocarditis due to COVID-19 infection in a pediatric patient in France. The study from Iran by Malekrah et al. <sup><xref ref-type="bibr" rid="B26">26</xref></sup> reported a rare cardiac complication caused by novel coronavirus disease in a 76-year-old man. The article by Purdy et al. <sup><xref ref-type="bibr" rid="B27">27</xref></sup> registered a case series of myocarditis in COVID-19 presenting with cardiogenic shock, in the United States of America, in two patients age 53 and 30 years old. The article by Tiwary et al. <sup><xref ref-type="bibr" rid="B28">28</xref></sup> reported a rare case of COVID-19 myocarditis with cardiac tamponade in a young adult with diabetes and renal failure, in the United States of America. In the study by Albdelazeem et al., <sup><xref ref-type="bibr" rid="B29">29</xref></sup> persistent cardiac magnetic resonance imaging (CMRI) features of myocarditis detected months after COVID-19 infection were described in a 41-year-old woman from the United States of America. Mathew et al. <sup><xref ref-type="bibr" rid="B30">30</xref></sup> reported subacute thyroiditis and heart failure in a patient presenting with COVID-19 in the United States of America. Veronese et al. <sup><xref ref-type="bibr" rid="B31">31</xref></sup> described fulminant myocarditis triggered by OC43 subtype coronavirus in an Italian patient. The study from the United States of America by Venkata et al. <sup><xref ref-type="bibr" rid="B32">32</xref></sup> registered a case of acute right ventricular dysfunction in a critically ill 67-year-old patient with COVID-19. Dabbagh et al. <sup><xref ref-type="bibr" rid="B33">33</xref></sup> registered a cardiac tamponade secondary to COVID-19 in a 67-year-old man from the United States of America. Mangiamelli et al. <sup><xref ref-type="bibr" rid="B34">34</xref></sup> described the feasibility of prone position coronary angiography in a patient with COVID-19 pneumonia and refractory hypoxemia from France and its consequences for the heart. Faraj et al. <sup><xref ref-type="bibr" rid="B35">35</xref></sup> described a case report of acute pericarditis revealing COVID-19 infection in a 36-year-old man in Morocco. In the Spanish study by Cardenes et al., <sup><xref ref-type="bibr" rid="B36">36</xref></sup> acute coronary syndrome (ACS) and shock in the context of acute COVID-19 infection were presented in a 74-year-old man. Bascu&#241;ana et al. <sup><xref ref-type="bibr" rid="B37">37</xref></sup> described thrombotic microangiopathy in a 40-year-old male kidney transplant patient with COVID-19 in the United States of America. Minhas et al. <sup><xref ref-type="bibr" rid="B38">38</xref></sup> reported a 58-year-old woman with Takotsubo syndrome in the setting of COVID-19 from the United States of America. The case report of a 71-year-old woman with complete heart block and COVID-19 infection in the United States of America was described by Haddadin et al. <sup><xref ref-type="bibr" rid="B39">39</xref></sup> Loghin et al., <sup><xref ref-type="bibr" rid="B40">40</xref></sup> in an article from the United States of America, described a pseudo-acute myocardial infarction in a young COVID-19 patient. The Spanish study by Rey et al. <sup><xref ref-type="bibr" rid="B41">41</xref></sup> registered COVID-19 infection and simultaneous thrombosis of two coronary arteries in a 59-year-old man. Nicol et al. <sup><xref ref-type="bibr" rid="B42">42</xref></sup> described delayed acute myocarditis and COVID-19&#8211;related multisystem inflammatory syndrome in a 40-year-old male patient from France. The Brazilian study by Yokoo et al. <sup><xref ref-type="bibr" rid="B43">43</xref></sup> described COVID-19 myocarditis in an 81-year-old man. Finally, Bernal-Torres et al. <sup><xref ref-type="bibr" rid="B44">44</xref></sup> reported COVID-19 fulminant myocarditis in a 38-year-old female Colombian patient with recent history of travel to Spain.</p>
        <p><xref ref-type="table" rid="t1">Table 1</xref> exhibits the identification of the articles included in the study.</p>
        <p>
          <table-wrap id="t1">
            <label>Table 1</label>
            <caption>
              <title>&#8211; Identification of the articles included in the study</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col/>
                <col/>
                <col/>
                <col/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Authors</th>
                  <th>Country</th>
                  <th>Type of study</th>
                  <th>Publication year</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td>Al-Assaf et al. <sup>23</sup></td>
                  <td align="center">United Arab Emirates</td>
                  <td align="center">Case Report</td>
                  <td align="center">2020</td>
                </tr>
                <tr>
                  <td>Nikoo et al. <sup>24</sup></td>
                  <td align="center">Iran</td>
                  <td align="center">Case Report</td>
                  <td align="center">2021</td>
                </tr>
                <tr>
                  <td>Fischer et al. <sup>25</sup></td>
                  <td align="center">France</td>
                  <td align="center">Case Report</td>
                  <td align="center">2020</td>
                </tr>
                <tr>
                  <td>Malekrah et al. <sup>26</sup></td>
                  <td align="center">Iran</td>
                  <td align="center">Case Report</td>
                  <td align="center">2020</td>
                </tr>
                <tr>
                  <td>Purdy et al <sup>27</sup></td>
                  <td align="center">United States of America</td>
                  <td align="center">Case Series</td>
                  <td align="center">2021</td>
                </tr>
                <tr>
                  <td>Tiwary et al. <sup>28</sup></td>
                  <td align="center">United States of America</td>
                  <td align="center">Case Report</td>
                  <td align="center">2020</td>
                </tr>
                <tr>
                  <td>Abdelazeem et al. <sup>29</sup></td>
                  <td align="center">United States of America</td>
                  <td align="center">Case Report</td>
                  <td align="center">2021</td>
                </tr>
                <tr>
                  <td>Mathews et al <sup>30</sup></td>
                  <td align="center">United States of America</td>
                  <td align="center">Case Report</td>
                  <td align="center">2021</td>
                </tr>
                <tr>
                  <td>Veronese et al. <sup>31</sup></td>
                  <td align="center">Italy</td>
                  <td align="center">Case Report</td>
                  <td align="center">2020</td>
                </tr>
                <tr>
                  <td>Venkata et al. <sup>32</sup></td>
                  <td align="center">United States of America</td>
                  <td align="center">Case Report</td>
                  <td align="center">2020</td>
                </tr>
                <tr>
                  <td>Dabbagh et al. <sup>33</sup></td>
                  <td align="center">United States of America</td>
                  <td align="center">Case Report</td>
                  <td align="center">2020</td>
                </tr>
                <tr>
                  <td>Mangiameli et al. <sup>34</sup></td>
                  <td align="center">France</td>
                  <td align="center">Case Report</td>
                  <td align="center">2020</td>
                </tr>
                <tr>
                  <td>Faraj et al. <sup>35</sup></td>
                  <td align="center">Morocco</td>
                  <td align="center">Case Report</td>
                  <td align="center">2021</td>
                </tr>
                <tr>
                  <td>C&#225;rdenes et al. <sup>36</sup></td>
                  <td align="center">Spain</td>
                  <td align="center">Case Report</td>
                  <td align="center">2020</td>
                </tr>
                <tr>
                  <td>Bascu&#241;ana et al. <sup>37</sup></td>
                  <td align="center">United States of America</td>
                  <td align="center">Case Report</td>
                  <td align="center">2020</td>
                </tr>
                <tr>
                  <td>Minhas et al. <sup>38</sup></td>
                  <td align="center">United States of America</td>
                  <td align="center">Case Report</td>
                  <td align="center">2020</td>
                </tr>
                <tr>
                  <td>Haddadin et al. <sup>39</sup></td>
                  <td align="center">United States of America</td>
                  <td align="center">Case Report</td>
                  <td align="center">2020</td>
                </tr>
                <tr>
                  <td>Loghin et al. <sup>40</sup></td>
                  <td align="center">United States of America</td>
                  <td align="center">Case Report</td>
                  <td align="center">2020</td>
                </tr>
                <tr>
                  <td>Rey et al. <sup>41</sup></td>
                  <td align="center">Spain</td>
                  <td align="center">Case Report</td>
                  <td align="center">2020</td>
                </tr>
                <tr>
                  <td>Nicol et al. <sup>42</sup></td>
                  <td align="center">France</td>
                  <td align="center">Case Report</td>
                  <td align="center">2020</td>
                </tr>
                <tr>
                  <td>Yokoo et al. <sup>43</sup></td>
                  <td align="center">Brazil</td>
                  <td align="center">Case Report</td>
                  <td align="center">2020</td>
                </tr>
                <tr>
                  <td>Bernal-Torres et al. <sup>44</sup></td>
                  <td align="center">Colombia</td>
                  <td align="center">Case Report</td>
                  <td align="center">2020</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
        </p>
      </sec>
      <sec>
        <title>Synthesis of Results</title>
        <sec>
          <title>Patient Profiles</title>
          <p>In the respective studies, the age group ranged from 15 to 81 years, with the mean age of 51 years. In addition, the male sex (63.6%) was the most prevalent.</p>
        </sec>
        <sec>
          <title>Clinical Manifestations</title>
          <p>Most patients had fever at hospital admission, accounting for 54.5% of the articles that reported myocarditis in COVID-19. <sup><xref ref-type="bibr" rid="B25">25</xref> - <xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B31">31</xref> , <xref ref-type="bibr" rid="B34">34</xref> , <xref ref-type="bibr" rid="B36">36</xref> - <xref ref-type="bibr" rid="B38">38</xref> , <xref ref-type="bibr" rid="B40">40</xref> - <xref ref-type="bibr" rid="B43">43</xref></sup> Subsequently, symptoms such as dyspnea (54.5%), <sup><xref ref-type="bibr" rid="B26">26</xref><xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B30">30</xref> - <xref ref-type="bibr" rid="B33">33</xref> , <xref ref-type="bibr" rid="B35">35</xref> - <xref ref-type="bibr" rid="B37">37</xref> , <xref ref-type="bibr" rid="B39">39</xref> , <xref ref-type="bibr" rid="B40">40</xref> , <xref ref-type="bibr" rid="B43">43</xref></sup> cough (45.4%), <sup><xref ref-type="bibr" rid="B26">26</xref> , <xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B29">29</xref> , <xref ref-type="bibr" rid="B32">32</xref> - <xref ref-type="bibr" rid="B34">34</xref> , <xref ref-type="bibr" rid="B38">38</xref> - <xref ref-type="bibr" rid="B41">41</xref></sup> and chest pain (22.7%), <sup><xref ref-type="bibr" rid="B24">24</xref> , <xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B28">28</xref> , <xref ref-type="bibr" rid="B29">29</xref> , <xref ref-type="bibr" rid="B35">35</xref></sup> respectively, affected patients ( <xref ref-type="table" rid="t2">Table 2</xref> ).</p>
          <p>
            <table-wrap id="t2">
              <label>Table 2</label>
              <caption>
                <title>&#8211; Clinical characteristics of the patients included in the study</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead>
                  <tr>
                    <th align="left">Authors</th>
                    <th>Age</th>
                    <th>Sex</th>
                    <th>Symptoms/ Clinical manifestations</th>
                    <th>Comorbidities</th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td>Al-Assaf et al. <sup>23</sup></td>
                    <td align="center">58-year-old</td>
                    <td align="center">Male</td>
                    <td align="center">Asymptomatic</td>
                    <td align="center">SAH</td>
                  </tr>
                  <tr>
                    <td>Nikoo et al. <sup>24</sup></td>
                    <td align="center">38-year-old</td>
                    <td align="center">Female</td>
                    <td align="center">Malaise, chest pain, nausea, vomiting</td>
                    <td align="center">Not informed</td>
                  </tr>
                  <tr>
                    <td>Fischer et al. <sup>25</sup></td>
                    <td align="center">15-year-old</td>
                    <td align="center">Male</td>
                    <td align="center">Chest pain, fever</td>
                    <td align="center">Not informed</td>
                  </tr>
                  <tr>
                    <td>Malekrah et al. <sup>26</sup></td>
                    <td align="center">71-year-old</td>
                    <td align="center">Male</td>
                    <td align="center">Weakness, fever, cough, dyspnea</td>
                    <td align="center">Not informed</td>
                  </tr>
                  <tr>
                    <td rowspan="2">Purdy et al. <sup>27</sup></td>
                    <td align="center">53-year-old</td>
                    <td align="center">Male</td>
                    <td align="center">Fever, cough, weak breath, tachycardia, tachypnea</td>
                    <td align="center">Not informed</td>
                  </tr>
                  <tr>
                    <td align="center">30-year-old</td>
                    <td align="center">Female</td>
                    <td align="center">Fatigue, weak breathing, tachycardia, tachypnea, hypotension</td>
                    <td align="center">Obesity</td>
                  </tr>
                  <tr>
                    <td>Tiwary et al. <sup>28</sup></td>
                    <td align="center">30-year-old</td>
                    <td align="center">Male</td>
                    <td align="center">Abdominal pain, chest pain, fatigue, vertigo</td>
                    <td align="center">DM1, obesity, SAH, glaucoma, diabetic nephropathy, and CKD</td>
                  </tr>
                  <tr>
                    <td>Abdelazeem et al. <sup>29</sup></td>
                    <td align="center">41-year-old</td>
                    <td align="center">Female</td>
                    <td align="center">Chest pain, cough</td>
                    <td align="center">Not informed</td>
                  </tr>
                  <tr>
                    <td>Mathews et al. <sup>30</sup></td>
                    <td align="center">67-year-old</td>
                    <td align="center">Male</td>
                    <td align="center">Diarrhea and dyspnea</td>
                    <td align="center">DM1, history of acute myocardial infarction, coronary artery disease, and CKD</td>
                  </tr>
                  <tr>
                    <td>Veronese et al. <sup>31</sup></td>
                    <td align="center">51-year-old</td>
                    <td align="center">Female</td>
                    <td align="center">Dyspnea, palpitations, fever</td>
                    <td align="center">Thalassemia minor</td>
                  </tr>
                  <tr>
                    <td>Venkata et al. <sup>32</sup></td>
                    <td align="center">67-year-old</td>
                    <td align="center">Male</td>
                    <td align="center">Malaise, anorexia, dry cough, dyspnea, severe respiratory distress</td>
                    <td align="center">Chronic obstructive pulmonary disease, CKD, DM2; history of hepatocellular carcinoma, rectal adenocarcinoma, and non-small cell lung cancer</td>
                  </tr>
                  <tr>
                    <td>Dabbagh et al. <sup>33</sup></td>
                    <td align="center">67-year-old</td>
                    <td align="center">Female</td>
                    <td align="center">Cough, pain in the left shoulder, severe dyspnea, and orthopnea</td>
                    <td align="center">Non-ischemic heart disease with LVEF of 15% in 2018, but improved to 40% after treatment</td>
                  </tr>
                  <tr>
                    <td>Mangiameli et al. <sup>34</sup></td>
                    <td align="center">57-year-old</td>
                    <td align="center">Female</td>
                    <td align="center">Fever, cough and severe fatigue</td>
                    <td align="center">Not informed</td>
                  </tr>
                  <tr>
                    <td>Faraj et al. <sup>35</sup></td>
                    <td align="center">36-year-old</td>
                    <td align="center">Male</td>
                    <td align="center">Chest pain and dyspnea</td>
                    <td align="center">Not informed</td>
                  </tr>
                  <tr>
                    <td>C&#225;rdenes et al. <sup>36</sup></td>
                    <td align="center">74-year-old</td>
                    <td align="center">Male</td>
                    <td align="center">General malaise, fever, dyspnea, and severe hypoxemia</td>
                    <td align="center">SAH, DM2, and history of hemorrhagic stroke</td>
                  </tr>
                  <tr>
                    <td>Bascu&#241;ana et al. <sup>37</sup></td>
                    <td align="center">40-year-old</td>
                    <td align="center">Male</td>
                    <td align="center">Fever, dyspnea, diarrhea, and abdominal pain</td>
                    <td align="center">CKD</td>
                  </tr>
                  <tr>
                    <td>Minhas et al. <sup>38</sup></td>
                    <td align="center">58-year-old</td>
                    <td align="center">Female</td>
                    <td align="center">Productive cough, fatigue, fever, and diarrhea</td>
                    <td align="center">DM2, SAH, and dyslipidemia</td>
                  </tr>
                  <tr>
                    <td>Haddadin et al. <sup>39</sup></td>
                    <td align="center">71-year-old</td>
                    <td align="center">Female</td>
                    <td align="center">Nonproductive cough, dyspnea at minimal efforts, orthopnea, and loss of smell and taste</td>
                    <td align="center">Parkinson&#8217;s disease, bipolar disorder, and DM2</td>
                  </tr>
                  <tr>
                    <td>Loghin et al. <sup>40</sup></td>
                    <td align="center">29-year-old</td>
                    <td align="center">Male</td>
                    <td align="center">Nonproductive cough, fever, myalgia, sore throat, malaise, and dyspnea</td>
                    <td align="center">No comorbidities</td>
                  </tr>
                  <tr>
                    <td>Rey et al. <sup>41</sup></td>
                    <td align="center">59-year-old</td>
                    <td align="center">Male</td>
                    <td align="center">Nonproductive cough, low fever, asthenia, and headache</td>
                    <td align="center">SAH, DM2, and history of hemorrhagic stroke</td>
                  </tr>
                  <tr>
                    <td>Nicol et al. <sup>42</sup></td>
                    <td align="center">40-year-old</td>
                    <td align="center">Male</td>
                    <td align="center">Fever, fatigue, anosmia, and myalgia</td>
                    <td align="center">Obesity</td>
                  </tr>
                  <tr>
                    <td>Yokoo et al. <sup>43</sup></td>
                    <td align="center">81-year-old</td>
                    <td align="center">Male</td>
                    <td align="center">Fever and dyspnea</td>
                    <td align="center">SAH</td>
                  </tr>
                  <tr>
                    <td>Bernal-Torres et al . <sup>44</sup></td>
                    <td align="center">38-year-old</td>
                    <td align="center">Female</td>
                    <td align="center">Palpitations</td>
                    <td align="center">No comorbidities</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN1">
                  <p>
                    <italic>CKD: chronic kidney disease; DM1: type 1 diabetes mellitus; DM2: type 2 diabetes mellitus; SAH: systemic arterial hypertension.</italic>
                  </p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </p>
        </sec>
        <sec>
          <title>Comorbidities</title>
          <p>Regarding the comorbidities associated with the clinical status of the patients, the most prevalent were systemic arterial hypertension (27.3%) <sup><xref ref-type="bibr" rid="B23">23</xref> , <xref ref-type="bibr" rid="B28">28</xref> , <xref ref-type="bibr" rid="B36">36</xref> , <xref ref-type="bibr" rid="B38">38</xref> , <xref ref-type="bibr" rid="B41">41</xref> , <xref ref-type="bibr" rid="B43">43</xref></sup> and type 2 diabetes mellitus (22.7%). <sup><xref ref-type="bibr" rid="B32">32</xref> , <xref ref-type="bibr" rid="B36">36</xref> , <xref ref-type="bibr" rid="B38">38</xref> , <xref ref-type="bibr" rid="B39">39</xref> , <xref ref-type="bibr" rid="B41">41</xref></sup> However, it is worth noting that 31.8% of the patients did not present comorbidities, <sup><xref ref-type="bibr" rid="B23">23</xref> , <xref ref-type="bibr" rid="B26">26</xref> , <xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B34">34</xref> , <xref ref-type="bibr" rid="B35">35</xref> , <xref ref-type="bibr" rid="B40">40</xref> , <xref ref-type="bibr" rid="B44">44</xref></sup> as shown in <xref ref-type="table" rid="t2">Table 2</xref> .</p>
        </sec>
        <sec>
          <title>ECG changes</title>
          <p>The ECG showed that most patients presented elevation of the ST segment (31.8%). <sup><xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B34">34</xref> , <xref ref-type="bibr" rid="B36">36</xref> , <xref ref-type="bibr" rid="B38">38</xref> , <xref ref-type="bibr" rid="B40">40</xref> , <xref ref-type="bibr" rid="B41">41</xref> , <xref ref-type="bibr" rid="B44">44</xref></sup> In addition, six studies (27.3%) reported normality in their patients, <sup><xref ref-type="bibr" rid="B24">24</xref> , <xref ref-type="bibr" rid="B30">30</xref> , <xref ref-type="bibr" rid="B32">32</xref> , <xref ref-type="bibr" rid="B35">35</xref> , <xref ref-type="bibr" rid="B37">37</xref> , <xref ref-type="bibr" rid="B42">42</xref></sup> as shown in <xref ref-type="table" rid="t3">Table 3</xref> .</p>
          <p>
            <table-wrap id="t3">
              <label>Table 3</label>
              <caption>
                <title>&#8211; Clinical Outcome</title>
              </caption>
              <table frame="hsides" rules="groups">
                <colgroup>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                  <col/>
                </colgroup>
                <thead>
                  <tr>
                    <th align="left">Authors</th>
                    <th>ECG changes</th>
                    <th>Echocardiogram changes</th>
                    <th>RT-PCR</th>
                    <th>CMRI Description</th>
                    <th>Hemodynamic Aspects</th>
                    <th>Treatment</th>
                    <th>Clinical Outcome</th>
                  </tr>
                </thead>
                <tbody>
                  <tr>
                    <td>Al-Assaf et al. <sup>23</sup></td>
                    <td align="center">Bradycardia, sinus rhythm, and 2:1 atrioventricular block</td>
                    <td align="center">Slightly dilated aorta</td>
                    <td align="center">Positive</td>
                    <td align="center">Edema of the interventricular septum and myocarditis</td>
                    <td align="center">No changes were recorded.</td>
                    <td align="center">Definitive cardiac pacemaker</td>
                    <td align="center">Hospital discharge</td>
                  </tr>
                  <tr>
                    <td>Nikoo et al. <sup>24</sup></td>
                    <td align="center">Sinus rhythm</td>
                    <td align="center">Diffuse hypokinesis with reduced LVEF of 20% to 25%</td>
                    <td align="center">Positive</td>
                    <td align="center">Diffuse myocardial inflammation of the left ventricular myocardium</td>
                    <td align="center">Hypotension; SaO <sub>2</sub> 92%; hypercoagulability; increased troponin I, prothrombin time, and INR; and hydroelectrolytic disorders</td>
                    <td align="center">Amiodarone; dexamethasone; temporary cardiac pacemaker</td>
                    <td align="center">Hospital discharge</td>
                  </tr>
                  <tr>
                    <td>Fischer et al. <sup>25</sup></td>
                    <td align="center">Diffuse elevation of the ST segment without reciprocal changes</td>
                    <td align="center">Mild diffuse hypokinesis with preserved LVEF (50%)</td>
                    <td align="center">Positive</td>
                    <td align="center">Moderate left ventricle dysfunction, involvement of posterolateral wall of the left ventricle related to acute myocardial edema, LGE, and myocarditis</td>
                    <td align="center">The hemodynamics of the patient remained stable. Increased high-sensivity troponin I was related.</td>
                    <td align="center">Bisoprolol; ramipril</td>
                    <td align="center">Hospital discharge</td>
                  </tr>
                  <tr>
                    <td>Malekrah et al. <sup>26</sup></td>
                    <td align="center">Intermittent block of the left branch; episodes of atrial fibrillation with bradycardia</td>
                    <td align="center">Normal</td>
                    <td align="center">Positive</td>
                    <td align="center">Not performed</td>
                    <td align="center">SaO <sub>2</sub> 85% and normal blood pressure</td>
                    <td align="center">Hydroxychloroquine; combination of lopinavir and ritonavir; permanent cardiac pacemaker</td>
                    <td align="center">Persistence of left branch block</td>
                  </tr>
                  <tr>
                    <td rowspan="2">Purdy et al. <sup>27</sup></td>
                    <td align="center">Sinus taquicardia with J-spot elevation in inferolateral leads</td>
                    <td align="center">Reduced LVEF (25%) with diffuse hypokinesis and moderately dilated right ventricle with reduced right ventricular function</td>
                    <td align="center">Positive</td>
                    <td align="center">Not performed</td>
                    <td align="center">Low cardiac output and cardiac index with progression to cardiogenic shock; SaO <sub>2</sub> 95%</td>
                    <td align="center">Methylprednisolone; hydroxychloroquine + empirical antibiotic; aspirin, atorvastatin, isosorbide, dinitrate, hydralazine, carvedilol, and eplerenone</td>
                    <td align="center">Hospital discharge</td>
                  </tr>
                  <tr>
                    <td align="center">Sinus tachycardia</td>
                    <td align="center">Reduced LVEF (45%), hypokinesis, and moderate pericardial effusion</td>
                    <td align="center">Positive</td>
                    <td align="center">Not performed</td>
                    <td align="center">Lactic acidosis, elevated NT-proBNP and D-dimer, and diagnosis with cardiogenic shock, which was treated</td>
                    <td align="center">Hydroxychloroquine, vitamin C, zinc, and atorvastatin</td>
                    <td align="center">Hospital discharge</td>
                  </tr>
                  <tr>
                    <td>Tiwary et al. <sup>28</sup></td>
                    <td align="center">Left bundle branch block</td>
                    <td align="center">Pericardial effusion, early right ventricular ventricle prolapse, and ventricular wall thickening</td>
                    <td align="center">Positive</td>
                    <td align="center">Not performed</td>
                    <td align="center">Increased troponin I, progressive hypotension, and progressive increase of fraction of inspired oxygen</td>
                    <td align="center">Norepinephrine and vasopressin, remdesivir, convalescent plasma, dexamethasone and cefepima + doxycycline</td>
                    <td align="center">Hospital discharge</td>
                  </tr>
                  <tr>
                    <td>Abdelazeem et al. <sup>29</sup></td>
                    <td align="center">Atrial fibrillation</td>
                    <td align="center">Left ventricular hypertrophy and infiltrative cardiomyopathy</td>
                    <td align="center">Positive</td>
                    <td align="center">Extensive myocarditis involving sub-epicardial and mid-wall of the left ventricular and interventricular septum</td>
                    <td align="center">Increased troponin I, increased BNP, and increased D-dimer</td>
                    <td align="center">Diltiazem, steroids, antibiotics, remdesivir, and convalescent plasma</td>
                    <td align="center">Hospital discharge</td>
                  </tr>
                  <tr>
                    <td>Mathews et al. <sup>30</sup></td>
                    <td align="center">Sinus rhythm</td>
                    <td align="center">Reduced LVEF (24%)</td>
                    <td align="center">Positive</td>
                    <td align="center">Not performed</td>
                    <td align="center">Increased troponin, increased NT-proBNP, and increased erythrocyte sedimentation rate</td>
                    <td align="center">Metimazole + prednisone</td>
                    <td align="center">Not informed</td>
                  </tr>
                  <tr>
                    <td>Veronese et al. <sup>31</sup></td>
                    <td align="center">Ventricular tachycardia</td>
                    <td align="center">Hypocontratile left ventricle, reduced LVEF (30%), and wall thickening</td>
                    <td align="center">Positive</td>
                    <td align="center">Biventricular functional recovery, diffuse edema recovery, LGE involving LV basal-lateral and basal-inferior walls, and myocarditis</td>
                    <td align="center">Cardiogenic shock with severe metabolic acidosis, increased troponin I, hypotension, signs of peripheral hypoperfusion, and SaO <sub>2</sub> 93%</td>
                    <td align="center">Mechanical circulatory support with intra-aortic balloon counterpulsation + veno-arterial extracorporeal membrane oxygenator + methylprednisolone pulse therapy</td>
                    <td align="center">Not informed</td>
                  </tr>
                  <tr>
                    <td>Venkata et al. <sup>32</sup></td>
                    <td align="center">Sinus rhythm</td>
                    <td align="center">Preserved LVEF, severely dilated right ventricle, and severe tricuspid regurgitation</td>
                    <td align="center">Positive</td>
                    <td align="center">Not performed</td>
                    <td align="center">Elevated high-sensitivity troponin I and D-dimer</td>
                    <td align="center">Ventilatory support in prone position, norepinephrine, and vasopressin</td>
                    <td align="center">Death</td>
                  </tr>
                  <tr>
                    <td>Dabbagh et al . <sup>33</sup></td>
                    <td align="center">Low voltage in member derivations</td>
                    <td align="center">Slightly reduced LVEF and pericardial effusion</td>
                    <td align="center">Positive</td>
                    <td align="center">Not performed</td>
                    <td align="center">Normal troponin I and midly elevated BNP</td>
                    <td align="center">Intubation, cardiac catheterization, hydroxychloroquine, colchicin, and glucocorticoids</td>
                    <td align="center">Hospital discharge</td>
                  </tr>
                  <tr>
                    <td>Mangiameli et al. <sup>34</sup></td>
                    <td align="center">ST-segment elevation in anteroseptal leads and ST-segment depression with T-wave inversion in DIII and aVF</td>
                    <td align="center">Anteroapical wall hypokinesis and reduced LVEF (20%)</td>
                    <td align="center">Positive</td>
                    <td align="center">Not performed</td>
                    <td align="center">Normal blood pressure, SaO <sub>2</sub> 81%, elevated high-sensitivity troponin T</td>
                    <td align="center">Emergency coronary angiography, nitroglycerin, and verapamil</td>
                    <td align="center">Death</td>
                  </tr>
                  <tr>
                    <td>Faraj et al. <sup>35</sup></td>
                    <td align="center">Sinus rhythm</td>
                    <td align="center">Pericardial effusion</td>
                    <td align="center">Positive</td>
                    <td align="center">Not performed</td>
                    <td align="center">Normal blood pressure, SaO <sub>2</sub> 85% to 88%, elevated platelet counts, and elevated ferritin</td>
                    <td align="center">Colchicin, vitamin C, vitamin D, zinc, and azithromycin</td>
                    <td align="center">Hospital discharge</td>
                  </tr>
                  <tr>
                    <td>C&#225;rdenes et al. <sup>36</sup></td>
                    <td align="center">Isolated elevation in D3 and ST unevenness in V2-V4</td>
                    <td align="center">Left ventricular dysfunction with inferolateral hypokinesis</td>
                    <td align="center">Positive</td>
                    <td align="center">Not performed</td>
                    <td align="center">Increased troponin T, D-dimer, BNP, and lactate dehydrogenase; septic shock and cardiogenic shock associated; hypercoagubility; and DIC</td>
                    <td align="center">Norepinephrine, emergency cardiac catheterization, percutaneous coronary intervention, and placement of 2 drug-eluting stents; hydroxychloroquine and tocilizumab</td>
                    <td align="center">Death</td>
                  </tr>
                  <tr>
                    <td>Bascu&#241;ana et al. <sup>37</sup></td>
                    <td align="center">Sinus rhythm</td>
                    <td align="center">No changes</td>
                    <td align="center">Positive</td>
                    <td align="center">Not performed</td>
                    <td align="center">Normal blood pressure, SaO <sub>2</sub> 93%, lymphopenia, thrombocytopenia, high serum C-reactive protein and D-dimer levels, high-sensitivity cardiac troponin I level, metabolic acidosis, anemia, and elevated lactate dehydrogenase</td>
                    <td align="center">Oxygen therapy, volume replacement, hydroxychloroquine, azithromycin, and methylprednisolone</td>
                    <td align="center">Hospital discharge</td>
                  </tr>
                  <tr>
                    <td>Minhas et al. <sup>38</sup></td>
                    <td align="center">Sinus tachycardia and ST segment elevation in I and aVL leads</td>
                    <td align="center">Reduced LVEF (20%)</td>
                    <td align="center">Positive</td>
                    <td align="center">Not performed</td>
                    <td align="center">High blood presure, SaO <sub>2</sub> 82%, increased troponin I level, and evolution to cardiogenic shock</td>
                    <td align="center">Dual antiplatelet therapy, heparin, hydroxychloroquine, and azithromycin</td>
                    <td align="center">Death</td>
                  </tr>
                  <tr>
                    <td>Haddadin et al. <sup>39</sup></td>
                    <td align="center">Complete heart block with junctional ventricular escape rhythm</td>
                    <td align="center">Thickened mitral valve leaflets and dilated left atrium</td>
                    <td align="center">Positive</td>
                    <td align="center">Not performed</td>
                    <td align="center">High blood pressure, SaO <sub>2</sub> 97%, leukocytosis, anemia, hyponatremia, elevated C-reactive protein, and elevated fibrinogen</td>
                    <td align="center">Introduction of dual camera cardiac pacemaker</td>
                    <td align="center">Death</td>
                  </tr>
                  <tr>
                    <td>Loghin et al. <sup>40</sup></td>
                    <td align="center">Sinus taquicardia and ST elevation in leads II, III, aVF, and V6</td>
                    <td align="center">No changes</td>
                    <td align="center">Positive</td>
                    <td align="center">Myocardial edema and myocarditis</td>
                    <td align="center">Hemodynamic stability</td>
                    <td align="center">Orotracheal intubation</td>
                    <td align="center">Hospital discharge</td>
                  </tr>
                  <tr>
                    <td>Rey et al. <sup>41</sup></td>
                    <td align="center">ST-segment elevation in the lower leads and v4 to V6, Q wave, and first degree atrioventricular block</td>
                    <td align="center">No changes</td>
                    <td align="center">Positive</td>
                    <td align="center">Not performed</td>
                    <td align="center">Thrombocytosis, atherosclerotic plaque rupture, high blood pressure, SaO <sub>2</sub> 92%, elevated C-reactive protein, elevated D-dimer, and DIC</td>
                    <td align="center">Tirofiban, aspirin, plasugrel, enoxaparin, hydroxychloroquine, ceftriaxone, and azithromycin</td>
                    <td align="center">Death</td>
                  </tr>
                  <tr>
                    <td>Nicol et al. <sup>42</sup></td>
                    <td align="center">Sinus tachycardia</td>
                    <td align="center">Reduced LVEF (45%), low cardiac output, and small pericardial effusion</td>
                    <td align="center">Positive</td>
                    <td align="center">Systolic dysfunction with global hypokinesia, myocardial inflammation, pericardial effusion, myocarditis, and LGE</td>
                    <td align="center">High blood pressure; elevated BNP, C-reactive protein, fibrinogen, procalcitonin, D-dimer, and cardiac troponin (high-sensitivity troponin I)</td>
                    <td align="center">Angiotensin-converting enzyme inhibitors, beta blockers, and antibiotic</td>
                    <td align="center">Hospital discharge</td>
                  </tr>
                  <tr>
                    <td>Yokoo et al. <sup>43</sup></td>
                    <td align="center">Showed no signs of ischemia</td>
                    <td align="center">Reduced LVEF (35%)</td>
                    <td align="center">Positive</td>
                    <td align="center">Ischemic pattern on the left ventricle base septum wall, diffuse hypokinesia, global systolic function involvement, myocarditis, and LGE areas with an ischemic pattern on the left ventricle base septum wall</td>
                    <td align="center">SaO <sub>2</sub> 91% and high troponin T</td>
                    <td align="center">Antibiotics, steroids, and hemodynamic monitoring</td>
                    <td align="center">Hospital discharge</td>
                  </tr>
                  <tr>
                    <td>Bernal-Torres et al. <sup>44</sup></td>
                    <td align="center">Diffuse elevation of the ST segment, with depression of the PR segment and Spodick sign</td>
                    <td align="center">Reduced LVEF (30%), global hypokinesis, and mild pericardial effusion</td>
                    <td align="center">Positive</td>
                    <td align="center">Transmural extent of myocardial edema to both ventricles, myocarditis, and left ventricular LGE</td>
                    <td align="center">Elevated jugular venous pressure, hypontesion, cardiogenic shock, SaO <sub>2</sub> 95%, metabolic acidosis, and increased troponin I and BNP</td>
                    <td align="center">Oxygen therapy, methylprednisolone, human immunoglobulin, hydroxychloroquine, azithromycin, norepinephrine, dobutamine, levosimendan, and furosemide</td>
                    <td align="center">Hospital discharge</td>
                  </tr>
                </tbody>
              </table>
              <table-wrap-foot>
                <fn id="TFN2">
                  <p>
                    <italic>BNP: type B natriuretic peptide; DIC: disseminated intravascular coagulation; LGE: late gadolinium enhancement; LVEF: left ventricular ejection fraction; RT-PCR: reverse-transcriptase chain reaction; PR Segment: the period of the electrocardiogram from the beginning of the P wave to the beginning of the Q wave; SaO2: oxygen saturation; ECG: electrocardiogram; CMRI: cardiac magnetic resonance imaging.</italic>
                  </p>
                </fn>
              </table-wrap-foot>
            </table-wrap>
          </p>
        </sec>
        <sec>
          <title>Changes in Echocardiogram</title>
          <p>When observing the results of the echocardiograms presented in the studies, the presence of hypokinesis (31.8%), <sup><xref ref-type="bibr" rid="B24">24</xref> , <xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B31">31</xref> , <xref ref-type="bibr" rid="B34">34</xref> , <xref ref-type="bibr" rid="B36">36</xref> , <xref ref-type="bibr" rid="B44">44</xref></sup> left ventricular ejection fraction below 50% (45.5%), <sup><xref ref-type="bibr" rid="B24">24</xref> , <xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B30">30</xref> , <xref ref-type="bibr" rid="B31">31</xref> , <xref ref-type="bibr" rid="B33">33</xref> , <xref ref-type="bibr" rid="B34">34</xref> , <xref ref-type="bibr" rid="B38">38</xref> , <xref ref-type="bibr" rid="B42">42</xref> - <xref ref-type="bibr" rid="B44">44</xref></sup> and pericardial effusion (27.3%) were significant. <sup><xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B28">28</xref> , <xref ref-type="bibr" rid="B33">33</xref> , <xref ref-type="bibr" rid="B35">35</xref> , <xref ref-type="bibr" rid="B42">42</xref> , <xref ref-type="bibr" rid="B44">44</xref></sup></p>
        </sec>
        <sec>
          <title>Cardiac Magnetic Resonance Imaging</title>
          <p>CMRI was performed in 40.9% of the studies. <sup><xref ref-type="bibr" rid="B23">23</xref> - <xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B29">29</xref> , <xref ref-type="bibr" rid="B31">31</xref> , <xref ref-type="bibr" rid="B40">40</xref> , <xref ref-type="bibr" rid="B42">42</xref> - <xref ref-type="bibr" rid="B44">44</xref></sup> The presence of myocarditis (88.8%), <sup><xref ref-type="bibr" rid="B23">23</xref> , <xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B29">29</xref> , <xref ref-type="bibr" rid="B31">31</xref> , <xref ref-type="bibr" rid="B40">40</xref> , <xref ref-type="bibr" rid="B42">42</xref> - <xref ref-type="bibr" rid="B44">44</xref></sup> edema (66.6%), <sup><xref ref-type="bibr" rid="B23">23</xref> , <xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B31">31</xref> , <xref ref-type="bibr" rid="B40">40</xref> , <xref ref-type="bibr" rid="B44">44</xref></sup> myocardial inflammation (66.6%), <sup><xref ref-type="bibr" rid="B23">23</xref> , <xref ref-type="bibr" rid="B24">24</xref> , <xref ref-type="bibr" rid="B29">29</xref> , <xref ref-type="bibr" rid="B42">42</xref> , <xref ref-type="bibr" rid="B43">43</xref></sup> and late gadolinium enhancement (LGE) (55.5%) <sup><xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B31">31</xref> , <xref ref-type="bibr" rid="B42">42</xref> - <xref ref-type="bibr" rid="B44">44</xref></sup> were the most frequent characteristics among the studies that reported CMRI.</p>
        </sec>
        <sec>
          <title>Hemodynamic Aspects</title>
          <p>The increased levels of troponin I or troponin T (63.6%) <sup><xref ref-type="bibr" rid="B24">24</xref> , <xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B28">28</xref> - <xref ref-type="bibr" rid="B34">34</xref> , <xref ref-type="bibr" rid="B36">36</xref> - <xref ref-type="bibr" rid="B38">38</xref> , <xref ref-type="bibr" rid="B42">42</xref> - <xref ref-type="bibr" rid="B44">44</xref></sup> were the most recurrent hemodynamic alterations in patients who developed cardiac involvement due to COVID-19. There were frequent reports of oxygen saturation (SaO <sub>2</sub> ) below 95% (40.9%), <sup><xref ref-type="bibr" rid="B24">24</xref> , <xref ref-type="bibr" rid="B26">26</xref> , <xref ref-type="bibr" rid="B31">31</xref> , <xref ref-type="bibr" rid="B34">34</xref> , <xref ref-type="bibr" rid="B35">35</xref> , <xref ref-type="bibr" rid="B37">37</xref> , <xref ref-type="bibr" rid="B38">38</xref> , <xref ref-type="bibr" rid="B41">41</xref> , <xref ref-type="bibr" rid="B43">43</xref></sup> increased D-dimer (31.8%), <sup><xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B29">29</xref> , <xref ref-type="bibr" rid="B32">32</xref> , <xref ref-type="bibr" rid="B36">36</xref> , <xref ref-type="bibr" rid="B37">37</xref> , <xref ref-type="bibr" rid="B41">41</xref> , <xref ref-type="bibr" rid="B42">42</xref></sup> evolution of patients to cardiogenic shock (22.7%), <sup><xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B31">31</xref> , <xref ref-type="bibr" rid="B36">36</xref> , <xref ref-type="bibr" rid="B38">38</xref> , <xref ref-type="bibr" rid="B44">44</xref></sup> and occurrence of metabolic acidosis (18.1%). <sup><xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B31">31</xref> , <xref ref-type="bibr" rid="B37">37</xref> , <xref ref-type="bibr" rid="B44">44</xref></sup></p>
        </sec>
        <sec>
          <title>Management</title>
          <p>It is possible to observe that the treatment varied, from more conservative to more invasive treatments. For the most part, treatment was based on the use of drugs (72.4%), such as antibiotics, <sup><xref ref-type="bibr" rid="B27">27</xref> - <xref ref-type="bibr" rid="B29">29</xref> , <xref ref-type="bibr" rid="B35">35</xref> , <xref ref-type="bibr" rid="B37">37</xref> , <xref ref-type="bibr" rid="B38">38</xref> , <xref ref-type="bibr" rid="B41">41</xref> - <xref ref-type="bibr" rid="B44">44</xref></sup> antimalarials, <sup><xref ref-type="bibr" rid="B26">26</xref> , <xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B33">33</xref> , <xref ref-type="bibr" rid="B36">36</xref> - <xref ref-type="bibr" rid="B38">38</xref> , <xref ref-type="bibr" rid="B41">41</xref> , <xref ref-type="bibr" rid="B44">44</xref></sup> antihypertensive, <sup><xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B34">34</xref> , <xref ref-type="bibr" rid="B42">42</xref> , <xref ref-type="bibr" rid="B44">44</xref></sup> antiarrhythmic, <sup><xref ref-type="bibr" rid="B24">24</xref> , <xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B29">29</xref> , <xref ref-type="bibr" rid="B34">34</xref> , <xref ref-type="bibr" rid="B42">42</xref> , <xref ref-type="bibr" rid="B44">44</xref></sup> antiretroviral, <sup><xref ref-type="bibr" rid="B26">26</xref> , <xref ref-type="bibr" rid="B28">28</xref> , <xref ref-type="bibr" rid="B29">29</xref></sup> corticosteroids, <sup><xref ref-type="bibr" rid="B24">24</xref> , <xref ref-type="bibr" rid="B27">27</xref> - <xref ref-type="bibr" rid="B31">31</xref> , <xref ref-type="bibr" rid="B33">33</xref> , <xref ref-type="bibr" rid="B37">37</xref> , <xref ref-type="bibr" rid="B43">43</xref> , <xref ref-type="bibr" rid="B44">44</xref></sup> and others. Others were managed with procedures, associated or not with medical therapy, such as pacemaker implantation (18.1%) <sup><xref ref-type="bibr" rid="B23">23</xref> , <xref ref-type="bibr" rid="B24">24</xref> , <xref ref-type="bibr" rid="B26">26</xref> , <xref ref-type="bibr" rid="B39">39</xref></sup> and orotracheal intubation (13.6%). <sup><xref ref-type="bibr" rid="B32">32</xref> , <xref ref-type="bibr" rid="B33">33</xref> , <xref ref-type="bibr" rid="B40">40</xref></sup></p>
        </sec>
        <sec>
          <title>Clinical Outcome</title>
          <p>Hospital discharge was prevalent in 59.1% of cases. <sup><xref ref-type="bibr" rid="B23">23</xref> - <xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B27">27</xref> - <xref ref-type="bibr" rid="B29">29</xref> , <xref ref-type="bibr" rid="B33">33</xref> , <xref ref-type="bibr" rid="B35">35</xref> , <xref ref-type="bibr" rid="B37">37</xref> , <xref ref-type="bibr" rid="B42">42</xref> - <xref ref-type="bibr" rid="B44">44</xref></sup> However, in 27.3% of the studies, the patients died, and these clinical outcomes were the most representative. <sup><xref ref-type="bibr" rid="B32">32</xref> , <xref ref-type="bibr" rid="B34">34</xref> , <xref ref-type="bibr" rid="B36">36</xref> , <xref ref-type="bibr" rid="B38">38</xref> , <xref ref-type="bibr" rid="B39">39</xref> , <xref ref-type="bibr" rid="B41">41</xref></sup><xref ref-type="table" rid="t3">Table 3</xref> summarizes the data.</p>
        </sec>
        <sec>
          <title>Risk of Bias across the Studies</title>
          <p>Due to the nature of the descriptive studies, the results presented are liable to investigator bias, selection procedure bias, and selection bias.</p>
        </sec>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>SARS-CoV-2 is a beta coronavirus that presents the composition of a positive enveloped RNA simple tape structure. It belongs to the subfamily Coronavirinae. The virus invades the human cell by binding with ACE2, a protein present in the cell membrane that is present in the cardiovascular epithelium. With its entry into the cellular environment, it migrates to the inside of the core for replication and apoptosis. <sup><xref ref-type="bibr" rid="B10">10</xref> , <xref ref-type="bibr" rid="B45">45</xref></sup></p>
      <p>The pathophysiology of severe COVID-19 has not yet been fully elucidated. However, the presence of a pro-inflammatory peak, known as a cytokine storm has been observed. <sup><xref ref-type="bibr" rid="B43">43</xref></sup> The damage caused by COVID-19 to the cardiovascular system is multifactorial, and it can result in a disorder between the high metabolic demand of cardiac tissue and low cardiac reserve, thrombogenesis, inflammation on a systemic level, and injury to cardiac tissue by the invasion of the virus to the myocardium. Generally, the most severe cases of acute cardiac injury occur in patients with preexisting comorbidities, such as diabetes mellitus, systemic arterial hypertension, chronic kidney disease, and cardiovascular disease, which are linked to a worse clinical prognosis. <sup><xref ref-type="bibr" rid="B46">46</xref> , <xref ref-type="bibr" rid="B47">47</xref></sup> These characteristics were observed in this study where we noticed that, in 31.8% (n = 7) of the studies in which the patients died, <sup><xref ref-type="bibr" rid="B32">32</xref> , <xref ref-type="bibr" rid="B34">34</xref> , <xref ref-type="bibr" rid="B36">36</xref> , <xref ref-type="bibr" rid="B38">38</xref> - <xref ref-type="bibr" rid="B41">41</xref></sup> 71.4% (n = 5) had registered comorbidities. <sup><xref ref-type="bibr" rid="B32">32</xref> , <xref ref-type="bibr" rid="B36">36</xref> , <xref ref-type="bibr" rid="B38">38</xref> , <xref ref-type="bibr" rid="B39">39</xref> , <xref ref-type="bibr" rid="B41">41</xref></sup></p>
      <p>Myocarditis presents various clinical manifestations, from mild symptoms, such as chest pain, palpitations, and fatigue, to cardiogenic shock or sudden cardiac death due to association with ventricular arrhythmias. <sup><xref ref-type="bibr" rid="B4">4</xref> , <xref ref-type="bibr" rid="B12">12</xref> - <xref ref-type="bibr" rid="B14">14</xref> , <xref ref-type="bibr" rid="B47">47</xref></sup> In myocarditis, there is focal or global myocardial inflammation, necrosis, and even ventricular dysfunction. The suspicion of focal myocarditis is raised in the presence of chest pain after a syndrome that is similar to influenza, thus presenting clinical evidence that points to an ACS for ECG or laboratory tests, or even with the presentation of cardiac wall movement abnormalities, but without evidence of an obstructive coronary artery disease for coronary angiography. <sup><xref ref-type="bibr" rid="B2">2</xref> , <xref ref-type="bibr" rid="B5">5</xref> , <xref ref-type="bibr" rid="B11">11</xref> , <xref ref-type="bibr" rid="B46">46</xref> , <xref ref-type="bibr" rid="B48">48</xref> - <xref ref-type="bibr" rid="B52">52</xref></sup></p>
      <p>The mechanisms and manifestations of cardiac arrhythmia are variable and include supraventricular tachycardia, polymorphic ventricular tachycardia, and torsade. However, the etiology of these abnormalities is still unclear. They may come from the disease itself through the inflammatory cascade, myocarditis, and hypoxia, or from the therapies based on chloroquine, hydroxychloroquine, moxifloxacin, and azithromycin. <sup><xref ref-type="bibr" rid="B47">47</xref> - <xref ref-type="bibr" rid="B49">49</xref></sup> In our study, the use of these medications was reported in 54.5% of the studies in which there was cardiac involvement after diagnosis of COVID-19. <sup><xref ref-type="bibr" rid="B26">26</xref> - <xref ref-type="bibr" rid="B29">29</xref> , <xref ref-type="bibr" rid="B33">33</xref> , <xref ref-type="bibr" rid="B35">35</xref> - <xref ref-type="bibr" rid="B37">37</xref> , <xref ref-type="bibr" rid="B41">41</xref> - <xref ref-type="bibr" rid="B44">44</xref></sup></p>
      <p>Acute respiratory infection caused by SARS-CoV-2 may be linked to an increased risk for classic myocardial infarction, as it is already known that inflammatory responses in the endothelium, such as that occurring in COVID-19, can increase the occurrence of plaque rupture. <sup><xref ref-type="bibr" rid="B48">48</xref></sup></p>
      <p>Transthoracic echocardiography is more likely to detect changes in contractility of the ventricular segment, perfused by the coronary artery, which is involved in patients with ACS. Therefore, echocardiography may be an aid tool for differential diagnosis between myocarditis and ACS resulting from COVID-19 infection. <sup><xref ref-type="bibr" rid="B45">45</xref> , <xref ref-type="bibr" rid="B46">46</xref> , <xref ref-type="bibr" rid="B53">53</xref> , <xref ref-type="bibr" rid="B54">54</xref></sup></p>
      <p>For myocarditis, we usually find diffuse hypokinesis with a reduction of ventricular ejection fraction, with possible presentation of a slightly associated pericardial effusion; however, segmental dyskinesia may also occur with even a hypodynamic state. Myocarditis may also clinically present with preserved ventricular function, with no change to segmental ventricular contractility in echocardiography. <sup><xref ref-type="bibr" rid="B14">14</xref> , <xref ref-type="bibr" rid="B45">45</xref></sup></p>
      <p>The most frequent alterations and characteristics found in echocardiography of patients with cardiac impairment are reduced left ventricular ejection fraction, pericardial effusion, global hypokinesis, left ventricular hypertrophy, diastolic dysfunction, pulmonary hypertension, and reduced overall longitudinal deformation. In the most severe cases, the following manifestations were observed: hyperdynamic phase, in which there is an increase in parameters for cardiac output and the left ventricular ejection fraction, with a consequent decrease in peripheral vascular resistance; acute cardiomyopathy generated by stress, which presents abnormalities for segmental contraction and ballooning of the apical region of the left ventricle (known as Takotsubo cardiomyopathy); acute pulmonary hypertension and right ventricular hypertrophy; and systolic and/or diastolic global dysfunction resulting from long-term anoxia, severe hypoxia, or systemic inflammation. <sup><xref ref-type="bibr" rid="B46">46</xref> , <xref ref-type="bibr" rid="B53">53</xref> - <xref ref-type="bibr" rid="B56">56</xref></sup> Regarding our study, we noticed that the most frequent manifestations on echocardiogram were similar to those already described in the literature, with significant presence of hypokinesis (31.9%), <sup><xref ref-type="bibr" rid="B24">24</xref> , <xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B31">31</xref> , <xref ref-type="bibr" rid="B34">34</xref> , <xref ref-type="bibr" rid="B36">36</xref> , <xref ref-type="bibr" rid="B44">44</xref></sup> reduced left ventricular ejection fraction (45.5%), <sup><xref ref-type="bibr" rid="B24">24</xref> , <xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B30">30</xref> , <xref ref-type="bibr" rid="B31">31</xref> , <xref ref-type="bibr" rid="B33">33</xref> , <xref ref-type="bibr" rid="B34">34</xref> , <xref ref-type="bibr" rid="B38">38</xref> , <xref ref-type="bibr" rid="B42">42</xref> - <xref ref-type="bibr" rid="B44">44</xref></sup> pericardial effusion (27.3%), <sup><xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B28">28</xref> , <xref ref-type="bibr" rid="B33">33</xref> , <xref ref-type="bibr" rid="B35">35</xref> , <xref ref-type="bibr" rid="B42">42</xref> , <xref ref-type="bibr" rid="B44">44</xref></sup> ventricular dysfunction (9.0%), <sup><xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B36">36</xref></sup> and ventricular hypertrophy (13.6%). <sup><xref ref-type="bibr" rid="B28">28</xref> , <xref ref-type="bibr" rid="B29">29</xref> , <xref ref-type="bibr" rid="B31">31</xref></sup></p>
      <p>Therefore, transthoracic echocardiography has been shown to be a means of early clinical evaluation of patients with SARS-CoV-2, since this method allows the visualization of hemodynamic evidence, capable of guiding the appropriate management. For patients with the most severe form of COVID-19, it is recommended to perform and evaluate daily echocardiography, as well as guidance for treatment that presents inotropic and/ or circulatory support. In this study, echocardiographic analysis proved to be of fundamental importance for the determination of the therapeutic strategies aimed at intervening favorably in the cardiac picture of the patient affected by the disease. We have observed the use of pacemakers (18.1%), <sup><xref ref-type="bibr" rid="B23">23</xref> , <xref ref-type="bibr" rid="B24">24</xref> , <xref ref-type="bibr" rid="B26">26</xref> , <xref ref-type="bibr" rid="B39">39</xref></sup> beta-blockers and other antiarrhythmics (31.8%), <sup><xref ref-type="bibr" rid="B24">24</xref> , <xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B29">29</xref> , <xref ref-type="bibr" rid="B34">34</xref> , <xref ref-type="bibr" rid="B42">42</xref> , <xref ref-type="bibr" rid="B44">44</xref></sup> ACE inhibitors (9.0%), <sup><xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B42">42</xref></sup> diuretics (18.1%), <sup><xref ref-type="bibr" rid="B27">27</xref> - <xref ref-type="bibr" rid="B29">29</xref> , <xref ref-type="bibr" rid="B44">44</xref></sup> in patients depending on the specific clinical need of each case, thus contributing to and corroborating previous analyses. <sup><xref ref-type="bibr" rid="B23">23</xref> , <xref ref-type="bibr" rid="B46">46</xref></sup></p>
      <p>The causative factors of the alterations observed in ECG induced by COVID-19 are not yet fully described. However, studies indicate that the virus can have a direct action on cardiomyocytes through an infiltration process with a consequent breakdown of the action potential of cells and structures, such as communicating junctions, causing several changes in the electrical conduction process. <sup><xref ref-type="bibr" rid="B57">57</xref> - <xref ref-type="bibr" rid="B59">59</xref></sup> Some of these abnormalities are still considered nonspecific but are highlighted in studies before the high frequency of ST-segment abnormalities; others that are more nonspecific, with variable appearance include: sinus tachycardia, atrioventricular block, occasional branch block, atrial fibrillation, bradycardia, premature atrial contractions, intraventricular block, and right branch block. <sup><xref ref-type="bibr" rid="B55">55</xref> - <xref ref-type="bibr" rid="B60">60</xref></sup> In our study, the elevation of the ST segment (31.9%) was the most characteristic change, <sup><xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B34">34</xref> , <xref ref-type="bibr" rid="B36">36</xref> , <xref ref-type="bibr" rid="B38">38</xref> , <xref ref-type="bibr" rid="B40">40</xref> , <xref ref-type="bibr" rid="B41">41</xref> , <xref ref-type="bibr" rid="B44">44</xref></sup> followed by atrioventricular or branch block (22.7%) <sup><xref ref-type="bibr" rid="B23">23</xref> , <xref ref-type="bibr" rid="B26">26</xref> , <xref ref-type="bibr" rid="B28">28</xref> , <xref ref-type="bibr" rid="B39">39</xref> , <xref ref-type="bibr" rid="B41">41</xref></sup> and sinus tachycardia (18.1%). <sup><xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B38">38</xref> , <xref ref-type="bibr" rid="B40">40</xref> , <xref ref-type="bibr" rid="B42">42</xref></sup> Notably, many cases showed sinus rhythm (27.3%). <sup><xref ref-type="bibr" rid="B24">24</xref> , <xref ref-type="bibr" rid="B30">30</xref> , <xref ref-type="bibr" rid="B32">32</xref> , <xref ref-type="bibr" rid="B35">35</xref> , <xref ref-type="bibr" rid="B37">37</xref> , <xref ref-type="bibr" rid="B42">42</xref></sup></p>
      <p>CMRI is an extremely useful imaging exam for analyzing myocardial structure and function, in addition to providing information about the composition of cardiac tissue less invasively than myocardial biopsy. <sup><xref ref-type="bibr" rid="B61">61</xref></sup> As for its use in cardiac impairment caused by COVID-19 evaluation, studies by Petersen et al., <sup><xref ref-type="bibr" rid="B61">61</xref></sup> Ojha et al., <sup><xref ref-type="bibr" rid="B62">62</xref></sup> and Shafiabadi Hassani et al. <sup><xref ref-type="bibr" rid="B63">63</xref></sup> described findings, such as myocarditis according to the Lake Louise criteria, <sup><xref ref-type="bibr" rid="B64">64</xref></sup> LGE (an imaging finding indicating tissue inflammation and early fibrosis), <sup><xref ref-type="bibr" rid="B65">65</xref></sup> edema, areas of nonischemic necrosis, pericardial effusion, and myocardial inflammatory activity causing damage to heart tissue. <sup><xref ref-type="bibr" rid="B61">61</xref> - <xref ref-type="bibr" rid="B63">63</xref></sup> Our study was similar to those described; CMRI was performed in 40.9% of studies, <sup><xref ref-type="bibr" rid="B23">23</xref> - <xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B29">29</xref> , <xref ref-type="bibr" rid="B31">31</xref> , <xref ref-type="bibr" rid="B40">40</xref> , <xref ref-type="bibr" rid="B42">42</xref> - <xref ref-type="bibr" rid="B44">44</xref></sup> reporting myocarditis (88.8% of those who performed CMRI) <sup><xref ref-type="bibr" rid="B23">23</xref> , <xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B29">29</xref> , <xref ref-type="bibr" rid="B31">31</xref> , <xref ref-type="bibr" rid="B40">40</xref> , <xref ref-type="bibr" rid="B42">42</xref> - <xref ref-type="bibr" rid="B44">44</xref></sup> edema (66.6% of those who performed CMRI) <sup><xref ref-type="bibr" rid="B23">23</xref> , <xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B31">31</xref> , <xref ref-type="bibr" rid="B40">40</xref> , <xref ref-type="bibr" rid="B44">44</xref></sup> description of myocardial inflammation (66.6% of those who underwent CMRI) <sup><xref ref-type="bibr" rid="B23">23</xref> , <xref ref-type="bibr" rid="B24">24</xref> , <xref ref-type="bibr" rid="B29">29</xref> , <xref ref-type="bibr" rid="B42">42</xref> , <xref ref-type="bibr" rid="B43">43</xref></sup> and LGE (55.5% of those who underwent CMRI). <sup><xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B31">31</xref> , <xref ref-type="bibr" rid="B42">42</xref> - <xref ref-type="bibr" rid="B44">44</xref></sup> Thus, this corroborates the usefulness of this test in assessing the degree of cardiovascular impairment in patients infected with SARS-CoV-2. <sup><xref ref-type="bibr" rid="B61">61</xref> - <xref ref-type="bibr" rid="B63">63</xref></sup></p>
      <p>COVID-19 can affect several organs and systems of the human body and cause hemodynamic impact. <sup><xref ref-type="bibr" rid="B66">66</xref></sup> The main characteristics described in the studies conducted by Sastry, Cuomo, and Muthusamy <sup><xref ref-type="bibr" rid="B67">67</xref></sup> and by Jasi&#324;ski and Stefaniak <sup><xref ref-type="bibr" rid="B68">68</xref></sup> include the occurrence of thromboembolic events, hypercoagulability, microangiopathies, respiratory failure, septic shock, cardiogenic shock, hypoxia, metabolic acidosis, renal injury, and myocardial stress. From this perspective, the results of our research corroborate with previous studies, since these characteristics were also recorded in the description of increased levels of cardiac troponins (63.6%), <sup><xref ref-type="bibr" rid="B24">24</xref> , <xref ref-type="bibr" rid="B25">25</xref> , <xref ref-type="bibr" rid="B28">28</xref> - <xref ref-type="bibr" rid="B34">34</xref> , <xref ref-type="bibr" rid="B36">36</xref> - <xref ref-type="bibr" rid="B38">38</xref> , <xref ref-type="bibr" rid="B42">42</xref> - <xref ref-type="bibr" rid="B44">44</xref></sup> indicating possible damage to myocardial function; <sup><xref ref-type="bibr" rid="B69">69</xref></sup> SaO <sub>2</sub> below 95% (40.9%); <sup><xref ref-type="bibr" rid="B24">24</xref> , <xref ref-type="bibr" rid="B26">26</xref> , <xref ref-type="bibr" rid="B31">31</xref> , <xref ref-type="bibr" rid="B34">34</xref> , <xref ref-type="bibr" rid="B35">35</xref> , <xref ref-type="bibr" rid="B37">37</xref> , <xref ref-type="bibr" rid="B38">38</xref> , <xref ref-type="bibr" rid="B41">41</xref> , <xref ref-type="bibr" rid="B43">43</xref></sup> increased D-dimer (31.8%), <sup><xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B29">29</xref> , <xref ref-type="bibr" rid="B32">32</xref> , <xref ref-type="bibr" rid="B36">36</xref> , <xref ref-type="bibr" rid="B37">37</xref> , <xref ref-type="bibr" rid="B41">41</xref> , <xref ref-type="bibr" rid="B42">42</xref></sup> which is an important biochemical marker whose increased serum levels indicate increased predisposition to thromboembolism; <sup><xref ref-type="bibr" rid="B70">70</xref></sup> evolution of patients to cardiogenic shock (22.7%); <sup><xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B31">31</xref> , <xref ref-type="bibr" rid="B36">36</xref> , <xref ref-type="bibr" rid="B38">38</xref> , <xref ref-type="bibr" rid="B44">44</xref></sup> and occurrence of metabolic acidosis (18.1%). <sup><xref ref-type="bibr" rid="B27">27</xref> , <xref ref-type="bibr" rid="B31">31</xref> , <xref ref-type="bibr" rid="B37">37</xref> , <xref ref-type="bibr" rid="B44">44</xref></sup> This combination of factors has been reported to be directly involved in the pathogenesis of myocardial damage in the form of myocarditis and in infarction with and without atheroma plaque formation. <sup><xref ref-type="bibr" rid="B6">6</xref> , <xref ref-type="bibr" rid="B8">8</xref> , <xref ref-type="bibr" rid="B9">9</xref> , <xref ref-type="bibr" rid="B61">61</xref></sup></p>
      <p>Moreover, cytokines also play an important role in this aspect, with a different activity, since they are related to changes in the expression of calcium and potassium channels resulting from disturbances in the duration of the action potential. <sup><xref ref-type="bibr" rid="B58">58</xref></sup></p>
      <p>Most patients with SARS-CoV-2 show nonspecific characteristics for the manifestation of myocarditis, with a presentation of sinus tachycardia, including ST-segment elevation, nonspecific intraventricular conduction delay, and T-wave abnormalities, with inversion in the previous leads, and the occasional appearance of atrioventricular block, corroborating the results of our study. One of the possible factors indicated in previous studies as related to ECG alterations would be due to the effect of antivirals used. <sup><xref ref-type="bibr" rid="B49">49</xref> , <xref ref-type="bibr" rid="B52">52</xref> , <xref ref-type="bibr" rid="B57">57</xref> - <xref ref-type="bibr" rid="B59">59</xref></sup></p>
      <p>Thakore et al. <sup><xref ref-type="bibr" rid="B57">57</xref></sup> observed the relevance of QT interval (period of the ECG from the beginning of the Q wave to the end of the T wave) analysis among patients infected with COVID-19. In this retrospective study, it was observed that an increase of 10 ms in corrected QT interval was related to a 16% increase in the patient's chance of having a higher severity index and, therefore, a higher risk of fatal evolution, given that, among patients who died during hospitalizations, a significant portion had a longer corrected QT interval on baseline ECG. In other studies, ECG findings were also frequently found to be associated with echocardiogram demonstrating ejection fraction lower than 50%, hypokinesis, and slight wall thickening. <sup><xref ref-type="bibr" rid="B57">57</xref> , <xref ref-type="bibr" rid="B71">71</xref> - <xref ref-type="bibr" rid="B73">73</xref></sup></p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusion</title>
      <p>We conclude that the current systematic review provides a potential tool for the analysis of cardiac changes and implications of SARS-CoV-2 infection, with an emphasis on the main ECG and echocardiographic findings, but also with coverage of clinical characteristics, treatment, and outcomes. ST-segment and tachyarrhythmias are the most frequent changes in the ECG, while diffuse hypokinesis, reduced ejection fraction, and pericardial effusion are more present on the echocardiogram.</p>
      <p>The results obtained in this article corroborate previous studies&#8217; conclusions on the subject. Further epidemiological and clinical research is needed to better understand these conditions, as well as to establish therapies to provide a better prognosis.</p>
    </sec>
  </body>
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    <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><bold>Sources of Funding:</bold> There were no external funding sources for this study.</p>
      </fn>
    </fn-group>
  </back>
</article>
