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| *Studies have demonstrated that COVID-19 interacts with the cardiovascular system, thereby causing myocardial injury and dysfunction as well as increasing morbidity among patients with underlying cardiovascular conditions. | | *Studies have demonstrated that COVID-19 interacts with the cardiovascular system, thereby causing myocardial injury and dysfunction as well as increasing morbidity among patients with underlying cardiovascular conditions. |
| *Among patients with COVID-19, there is a high prevalence of the cardiovascular disease, and >7% of patients experience myocardial injury from the infection.<ref name="ClerkinFried2020">{{cite journal|last1=Clerkin|first1=Kevin J.|last2=Fried|first2=Justin A.|last3=Raikhelkar|first3=Jayant|last4=Sayer|first4=Gabriel|last5=Griffin|first5=Jan M.|last6=Masoumi|first6=Amirali|last7=Jain|first7=Sneha S.|last8=Burkhoff|first8=Daniel|last9=Kumaraiah|first9=Deepa|last10=Rabbani|first10=LeRoy|last11=Schwartz|first11=Allan|last12=Uriel|first12=Nir|title=COVID-19 and Cardiovascular Disease|journal=Circulation|volume=141|issue=20|year=2020|pages=1648–1655|issn=0009-7322|doi=10.1161/CIRCULATIONAHA.120.046941}}</ref> | | *Among patients with COVID-19, there is a high prevalence of the cardiovascular disease, and >7% of patients experience myocardial injury from the infection. |
| *[[Myocarditis]] is an inflammatory disease of the heart characterized by inflammatory infiltrates and myocardial injury without an ischemic cause.<ref name="EsfandiareiMcManus2008">{{cite journal|last1=Esfandiarei|first1=Mitra|last2=McManus|first2=Bruce M.|title=Molecular Biology and Pathogenesis of Viral Myocarditis|journal=Annual Review of Pathology: Mechanisms of Disease|volume=3|issue=1|year=2008|pages=127–155|issn=1553-4006|doi=10.1146/annurev.pathmechdis.3.121806.151534}}</ref> | | *[[Myocarditis]] is an inflammatory disease of the heart characterized by inflammatory infiltrates and myocardial injury without an ischemic cause. |
| *The major cause of myocarditis in the United States and other developed countries is viral.<ref name="CaforioPankuweit2013">{{cite journal|last1=Caforio|first1=A. L. P.|last2=Pankuweit|first2=S.|last3=Arbustini|first3=E.|last4=Basso|first4=C.|last5=Gimeno-Blanes|first5=J.|last6=Felix|first6=S. B.|last7=Fu|first7=M.|last8=Helio|first8=T.|last9=Heymans|first9=S.|last10=Jahns|first10=R.|last11=Klingel|first11=K.|last12=Linhart|first12=A.|last13=Maisch|first13=B.|last14=McKenna|first14=W.|last15=Mogensen|first15=J.|last16=Pinto|first16=Y. M.|last17=Ristic|first17=A.|last18=Schultheiss|first18=H.-P.|last19=Seggewiss|first19=H.|last20=Tavazzi|first20=L.|last21=Thiene|first21=G.|last22=Yilmaz|first22=A.|last23=Charron|first23=P.|last24=Elliott|first24=P. M.|title=Current state of knowledge on aetiology, diagnosis, management, and therapy of myocarditis: A position statement of the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases|journal=European Heart Journal|volume=34|issue=33|year=2013|pages=2636–2648|issn=0195-668X|doi=10.1093/eurheartj/eht210}}</ref> <ref name="KociolCooper2020">{{cite journal|last1=Kociol|first1=Robb D.|last2=Cooper|first2=Leslie T.|last3=Fang|first3=James C.|last4=Moslehi|first4=Javid J.|last5=Pang|first5=Peter S.|last6=Sabe|first6=Marwa A.|last7=Shah|first7=Ravi V.|last8=Sims|first8=Daniel B.|last9=Thiene|first9=Gaetano|last10=Vardeny|first10=Orly|title=Recognition and Initial Management of Fulminant Myocarditis|journal=Circulation|volume=141|issue=6|year=2020|issn=0009-7322|doi=10.1161/CIR.0000000000000745}}</ref> Number of cases of myocarditis have been reported in COVID19 patients.<ref name="ZengLiu2020">{{cite journal|last1=Zeng|first1=Jia-Hui|last2=Liu|first2=Ying-Xia|last3=Yuan|first3=Jing|last4=Wang|first4=Fu-Xiang|last5=Wu|first5=Wei-Bo|last6=Li|first6=Jin-Xiu|last7=Wang|first7=Li-Fei|last8=Gao|first8=Hong|last9=Wang|first9=Yao|last10=Dong|first10=Chang-Feng|last11=Li|first11=Yi-Jun|last12=Xie|first12=Xiao-Juan|last13=Feng|first13=Cheng|last14=Liu|first14=Lei|title=First case of COVID-19 complicated with fulminant myocarditis: a case report and insights|journal=Infection|year=2020|issn=0300-8126|doi=10.1007/s15010-020-01424-5}}</ref><ref name="InciardiLupi2020">{{cite journal|last1=Inciardi|first1=Riccardo M.|last2=Lupi|first2=Laura|last3=Zaccone|first3=Gregorio|last4=Italia|first4=Leonardo|last5=Raffo|first5=Michela|last6=Tomasoni|first6=Daniela|last7=Cani|first7=Dario S.|last8=Cerini|first8=Manuel|last9=Farina|first9=Davide|last10=Gavazzi|first10=Emanuele|last11=Maroldi|first11=Roberto|last12=Adamo|first12=Marianna|last13=Ammirati|first13=Enrico|last14=Sinagra|first14=Gianfranco|last15=Lombardi|first15=Carlo M.|last16=Metra|first16=Marco|title=Cardiac Involvement in a Patient With Coronavirus Disease 2019 (COVID-19)|journal=JAMA Cardiology|year=2020|issn=2380-6583|doi=10.1001/jamacardio.2020.1096}}</ref><ref name="HanKim2020">{{cite journal|last1=Han|first1=Seongwook|last2=Kim|first2=Hyun Ah|last3=Kim|first3=Jin Young|last4=Kim|first4=In-Cheol|title=COVID-19-related myocarditis in a 21-year-old female patient|journal=European Heart Journal|volume=41|issue=19|year=2020|pages=1859–1859|issn=0195-668X|doi=10.1093/eurheartj/ehaa288}}</ref><ref name="EspositoGodino2020">{{cite journal|last1=Esposito|first1=Antonio|last2=Godino|first2=Cosmo|last3=Basso|first3=Cristina|last4=Cappelletti|first4=Alberto Maria|last5=Tresoldi|first5=Moreno|last6=De Cobelli|first6=Francesco|last7=Vignale|first7=Davide|last8=Villatore|first8=Andrea|last9=Palmisano|first9=Anna|last10=Gramegna|first10=Mario|last11=Peretto|first11=Giovanni|last12=Sala|first12=Simone|title=Acute myocarditis presenting as a reverse Tako-Tsubo syndrome in a patient with SARS-CoV-2 respiratory infection|journal=European Heart Journal|volume=41|issue=19|year=2020|pages=1861–1862|issn=0195-668X|doi=10.1093/eurheartj/ehaa286}}</ref> It has also been reported as the cause of death in some COVID19 patients.<ref name="RuanYang2020">{{cite journal|last1=Ruan|first1=Qiurong|last2=Yang|first2=Kun|last3=Wang|first3=Wenxia|last4=Jiang|first4=Lingyu|last5=Song|first5=Jianxin|title=Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China|journal=Intensive Care Medicine|volume=46|issue=5|year=2020|pages=846–848|issn=0342-4642|doi=10.1007/s00134-020-05991-x}}</ref> | | *The major cause of myocarditis in the United States and other developed countries is viral. Number of cases of myocarditis have been reported in COVID19 patients. |
| | *It has also been reported as the cause of death in some COVID19 patients. |
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| [[SARS-CoV-2]] infection is caused by binding of the viral surface spike protein (primed by [[TMPRSS2]], which is a [[transmembrane protease, serine 2]]) to the human [[angiotensin-converting enzyme 2 (ACE2) receptor]].<ref name="HoffmannKleine-Weber2020">{{cite journal|last1=Hoffmann|first1=Markus|last2=Kleine-Weber|first2=Hannah|last3=Schroeder|first3=Simon|last4=Krüger|first4=Nadine|last5=Herrler|first5=Tanja|last6=Erichsen|first6=Sandra|last7=Schiergens|first7=Tobias S.|last8=Herrler|first8=Georg|last9=Wu|first9=Nai-Huei|last10=Nitsche|first10=Andreas|last11=Müller|first11=Marcel A.|last12=Drosten|first12=Christian|last13=Pöhlmann|first13=Stefan|title=SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor|journal=Cell|volume=181|issue=2|year=2020|pages=271–280.e8|issn=00928674|doi=10.1016/j.cell.2020.02.052}}</ref> ACE2 is expressed in the lung, principally type II alveolar cells which appears to be the principal portal of entry.<ref name="ZhaoZhao2020">{{cite journal|last1=Zhao|first1=Yu|last2=Zhao|first2=Zixian|last3=Wang|first3=Yujia|last4=Zhou|first4=Yueqing|last5=Ma|first5=Yu|last6=Zuo|first6=Wei|year=2020|doi=10.1101/2020.01.26.919985}}</ref> [[ACE2]] is highly expressed in the heart as well.<ref name="TikellisThomas2012">{{cite journal|last1=Tikellis|first1=Chris|last2=Thomas|first2=M. C.|title=Angiotensin-Converting Enzyme 2 (ACE2) Is a Key Modulator of the Renin Angiotensin System in Health and Disease|journal=International Journal of Peptides|volume=2012|year=2012|pages=1–8|issn=1687-9767|doi=10.1155/2012/256294}}</ref> Naïve T lymphocytes can be primed for viral antigens via antigen-presenting cells and cardio-tropism by the heart-produced [[hepatocyte growth factor (HGF)]] which binds c-Met, an HGF receptor on T lymphocytes.<ref name="KomarowskaCoe2015">{{cite journal|last1=Komarowska|first1=Izabela|last2=Coe|first2=David|last3=Wang|first3=Guosu|last4=Haas|first4=Robert|last5=Mauro|first5=Claudio|last6=Kishore|first6=Madhav|last7=Cooper|first7=Dianne|last8=Nadkarni|first8=Suchita|last9=Fu|first9=Hongmei|last10=Steinbruchel|first10=Daniel A.|last11=Pitzalis|first11=Costantino|last12=Anderson|first12=Graham|last13=Bucy|first13=Pat|last14=Lombardi|first14=Giovanna|last15=Breckenridge|first15=Ross|last16=Marelli-Berg|first16=Federica M.|title=Hepatocyte Growth Factor Receptor c-Met Instructs T Cell Cardiotropism and Promotes T Cell Migration to the Heart via Autocrine Chemokine Release|journal=Immunity|volume=42|issue=6|year=2015|pages=1087–1099|issn=10747613|doi=10.1016/j.immuni.2015.05.014}}</ref> The viral RNAs of [[Middle East Respiratory Syndrome coronavirus]] [[(MERS-CoV)]] and [[SARS-CoV]] were found in the heart tissues of infected animals, suggesting that these coronaviruses possess [[cardiotropism]].<ref name="AgrawalGarron2015">{{cite journal|last1=Agrawal|first1=Anurodh Shankar|last2=Garron|first2=Tania|last3=Tao|first3=Xinrong|last4=Peng|first4=Bi-Hung|last5=Wakamiya|first5=Maki|last6=Chan|first6=Teh-Sheng|last7=Couch|first7=Robert B.|last8=Tseng|first8=Chien-Te K.|last9=García-Sastre|first9=A.|title=Generation of a Transgenic Mouse Model of Middle East Respiratory Syndrome Coronavirus Infection and Disease|journal=Journal of Virology|volume=89|issue=7|year=2015|pages=3659–3670|issn=0022-538X|doi=10.1128/JVI.03427-14}}</ref><ref name="SchaecherStabenow2008">{{cite journal|last1=Schaecher|first1=Scott R.|last2=Stabenow|first2=Jennifer|last3=Oberle|first3=Christina|last4=Schriewer|first4=Jill|last5=Buller|first5=R. Mark|last6=Sagartz|first6=John E.|last7=Pekosz|first7=Andrew|title=An immunosuppressed Syrian golden hamster model for SARS-CoV infection|journal=Virology|volume=380|issue=2|year=2008|pages=312–321|issn=00426822|doi=10.1016/j.virol.2008.07.026}}</ref> The primed CD8+ T lymphocytes migrate to the cardiomyocytes and through [[cell-mediated cytotoxicity]], cause myocardial inflammation. In the [[cytokine storm syndrome]], proinflammatory cytokines such as [[Interleukin-6]] ([[IL-6]]) are released into the circulation, which further augments T-lymphocyte activation and causes the release of more cytokines.<ref name="ZhouYu2020">{{cite journal|last1=Zhou|first1=Fei|last2=Yu|first2=Ting|last3=Du|first3=Ronghui|last4=Fan|first4=Guohui|last5=Liu|first5=Ying|last6=Liu|first6=Zhibo|last7=Xiang|first7=Jie|last8=Wang|first8=Yeming|last9=Song|first9=Bin|last10=Gu|first10=Xiaoying|last11=Guan|first11=Lulu|last12=Wei|first12=Yuan|last13=Li|first13=Hui|last14=Wu|first14=Xudong|last15=Xu|first15=Jiuyang|last16=Tu|first16=Shengjin|last17=Zhang|first17=Yi|last18=Chen|first18=Hua|last19=Cao|first19=Bin|title=Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study|journal=The Lancet|volume=395|issue=10229|year=2020|pages=1054–1062|issn=01406736|doi=10.1016/S0140-6736(20)30566-3}}</ref> This results in a positive feedback loop of immune activation and myocardial damage.<ref name="pmid409380">{{cite journal| author=Iakimov VP| title=[F. Engels' theory of the origin of man and modern anthropologic findings]. | journal=Arkh Anat Gistol Embriol | year= 1977 | volume= 72 | issue= 6 | pages= 5-11 | pmid=409380 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=409380 }} </ref><ref name="EsfandiareiMcManus2008">{{cite journal|last1=Esfandiarei|first1=Mitra|last2=McManus|first2=Bruce M.|title=Molecular Biology and Pathogenesis of Viral Myocarditis|journal=Annual Review of Pathology: Mechanisms of Disease|volume=3|issue=1|year=2008|pages=127–155|issn=1553-4006|doi=10.1146/annurev.pathmechdis.3.121806.151534}}</ref> | | * [[SARS-CoV-2]] infection is caused by binding of the viral surface spike protein (primed by [[TMPRSS2]], which is a trans-membrane protease, serine 2) to the human [[angiotensin-converting enzyme 2 (ACE2) receptor]]. |
| | * ACE2 is expressed in the lung, principally type II alveolar cells which appears to be the principal portal of entry. |
| | * [[ACE2]] is highly expressed in the heart as well. |
| | * Naive T lymphocytes can be primed for viral antigens via antigen-presenting cells and cardio-tropism by the heart-produced [[hepatocyte growth factor (HGF)]] which binds c-Met, an HGF receptor on T lymphocytes. |
| | * The viral RNAs of [[Middle East Respiratory Syndrome coronavirus]] [[(MERS-CoV)]] and [[SARS-CoV]] were found in the heart tissues of infected animals, suggesting that these corona viruses possess cardio-tropism. |
| | * The primed CD 8+ T lymphocytes migrate to the cardiomyocytes and through cell-mediated cytotoxicity, cause myocardial inflammation. |
| | * In the [[cytokine storm syndrome]], pro-inflammatory cytokines such as [[Interleukin-6]] ([[IL-6]]) are released into the circulation, which further augments T-lymphocyte activation and causes the release of more cytokines. |
| | * This results in a positive feedback loop of immune activation and myocardial damage.<ref name="EsfandiareiMcManus2008">{{cite journal|last1=Esfandiarei|first1=Mitra|last2=McManus|first2=Bruce M.|title=Molecular Biology and Pathogenesis of Viral Myocarditis|journal=Annual Review of Pathology: Mechanisms of Disease|volume=3|issue=1|year=2008|pages=127–155|issn=1553-4006|doi=10.1146/annurev.pathmechdis.3.121806.151534}}</ref> |
| | <references /> |