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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">COVID-19 in the heart and the lungs: could we “Notch” the inflammatory storm?</title><author><name sortKey="Rizzo, Paola" sort="Rizzo, Paola" uniqKey="Rizzo P" first="Paola" last="Rizzo">Paola Rizzo</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1757 2064</institution-id><institution-id institution-id-type="GRID">grid.8484.0</institution-id><institution>Department of Morphology, Surgery and Experimental Medicine and Laboratory for Technologies of Advanced Therapies (LTTA),</institution><institution>University of Ferrara,</institution></institution-wrap>Ferrara, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1785 1274</institution-id><institution-id institution-id-type="GRID">grid.417010.3</institution-id><institution>Maria Cecilia Hospital, GVM Care & Research,</institution></institution-wrap>Cotignola, Italy</nlm:aff></affiliation></author><author><name sortKey="Vieceli Dalla Sega, Francesco" sort="Vieceli Dalla Sega, Francesco" uniqKey="Vieceli Dalla Sega F" first="Francesco" last="Vieceli Dalla Sega">Francesco Vieceli Dalla Sega</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1785 1274</institution-id><institution-id institution-id-type="GRID">grid.417010.3</institution-id><institution>Maria Cecilia Hospital, GVM Care & Research,</institution></institution-wrap>Cotignola, Italy</nlm:aff></affiliation></author><author><name sortKey="Fortini, Francesca" sort="Fortini, Francesca" uniqKey="Fortini F" first="Francesca" last="Fortini">Francesca Fortini</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1785 1274</institution-id><institution-id institution-id-type="GRID">grid.417010.3</institution-id><institution>Maria Cecilia Hospital, GVM Care & Research,</institution></institution-wrap>Cotignola, Italy</nlm:aff></affiliation></author><author><name sortKey="Marracino, Luisa" sort="Marracino, Luisa" uniqKey="Marracino L" first="Luisa" last="Marracino">Luisa Marracino</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1757 2064</institution-id><institution-id institution-id-type="GRID">grid.8484.0</institution-id><institution>Department of Morphology, Surgery and Experimental Medicine and Laboratory for Technologies of Advanced Therapies (LTTA),</institution><institution>University of Ferrara,</institution></institution-wrap>Ferrara, Italy</nlm:aff></affiliation></author><author><name sortKey="Rapezzi, Claudio" sort="Rapezzi, Claudio" uniqKey="Rapezzi C" first="Claudio" last="Rapezzi">Claudio Rapezzi</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1785 1274</institution-id><institution-id institution-id-type="GRID">grid.417010.3</institution-id><institution>Maria Cecilia Hospital, GVM Care & Research,</institution></institution-wrap>Cotignola, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.416315.4</institution-id><institution>Cardiovascular Center,</institution><institution>University Hospital of Cona,</institution></institution-wrap>Ferrara, Italy</nlm:aff></affiliation></author><author><name sortKey="Ferrari, Roberto" sort="Ferrari, Roberto" uniqKey="Ferrari R" first="Roberto" last="Ferrari">Roberto Ferrari</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1785 1274</institution-id><institution-id institution-id-type="GRID">grid.417010.3</institution-id><institution>Maria Cecilia Hospital, GVM Care & Research,</institution></institution-wrap>Cotignola, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.416315.4</institution-id><institution>Cardiovascular Center,</institution><institution>University Hospital of Cona,</institution></institution-wrap>Ferrara, Italy</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32274570</idno><idno type="pmc">7144545</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144545</idno><idno type="RBID">PMC:7144545</idno><idno type="doi">10.1007/s00395-020-0791-5</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000194</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000194</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">COVID-19 in the heart and the lungs: could we “Notch” the inflammatory storm?</title><author><name sortKey="Rizzo, Paola" sort="Rizzo, Paola" uniqKey="Rizzo P" first="Paola" last="Rizzo">Paola Rizzo</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1757 2064</institution-id><institution-id institution-id-type="GRID">grid.8484.0</institution-id><institution>Department of Morphology, Surgery and Experimental Medicine and Laboratory for Technologies of Advanced Therapies (LTTA),</institution><institution>University of Ferrara,</institution></institution-wrap>Ferrara, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1785 1274</institution-id><institution-id institution-id-type="GRID">grid.417010.3</institution-id><institution>Maria Cecilia Hospital, GVM Care & Research,</institution></institution-wrap>Cotignola, Italy</nlm:aff></affiliation></author><author><name sortKey="Vieceli Dalla Sega, Francesco" sort="Vieceli Dalla Sega, Francesco" uniqKey="Vieceli Dalla Sega F" first="Francesco" last="Vieceli Dalla Sega">Francesco Vieceli Dalla Sega</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1785 1274</institution-id><institution-id institution-id-type="GRID">grid.417010.3</institution-id><institution>Maria Cecilia Hospital, GVM Care & Research,</institution></institution-wrap>Cotignola, Italy</nlm:aff></affiliation></author><author><name sortKey="Fortini, Francesca" sort="Fortini, Francesca" uniqKey="Fortini F" first="Francesca" last="Fortini">Francesca Fortini</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1785 1274</institution-id><institution-id institution-id-type="GRID">grid.417010.3</institution-id><institution>Maria Cecilia Hospital, GVM Care & Research,</institution></institution-wrap>Cotignola, Italy</nlm:aff></affiliation></author><author><name sortKey="Marracino, Luisa" sort="Marracino, Luisa" uniqKey="Marracino L" first="Luisa" last="Marracino">Luisa Marracino</name><affiliation><nlm:aff id="Aff1"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1757 2064</institution-id><institution-id institution-id-type="GRID">grid.8484.0</institution-id><institution>Department of Morphology, Surgery and Experimental Medicine and Laboratory for Technologies of Advanced Therapies (LTTA),</institution><institution>University of Ferrara,</institution></institution-wrap>Ferrara, Italy</nlm:aff></affiliation></author><author><name sortKey="Rapezzi, Claudio" sort="Rapezzi, Claudio" uniqKey="Rapezzi C" first="Claudio" last="Rapezzi">Claudio Rapezzi</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1785 1274</institution-id><institution-id institution-id-type="GRID">grid.417010.3</institution-id><institution>Maria Cecilia Hospital, GVM Care & Research,</institution></institution-wrap>Cotignola, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.416315.4</institution-id><institution>Cardiovascular Center,</institution><institution>University Hospital of Cona,</institution></institution-wrap>Ferrara, Italy</nlm:aff></affiliation></author><author><name sortKey="Ferrari, Roberto" sort="Ferrari, Roberto" uniqKey="Ferrari R" first="Roberto" last="Ferrari">Roberto Ferrari</name><affiliation><nlm:aff id="Aff2"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1785 1274</institution-id><institution-id institution-id-type="GRID">grid.417010.3</institution-id><institution>Maria Cecilia Hospital, GVM Care & Research,</institution></institution-wrap>Cotignola, Italy</nlm:aff></affiliation><affiliation><nlm:aff id="Aff3"><institution-wrap><institution-id institution-id-type="GRID">grid.416315.4</institution-id><institution>Cardiovascular Center,</institution><institution>University Hospital of Cona,</institution></institution-wrap>Ferrara, Italy</nlm:aff></affiliation></author></analytic><series><title level="j">Basic Research in Cardiology</title><idno type="ISSN">0300-8428</idno><idno type="eISSN">1435-1803</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p id="Par1">From January 2020, coronavirus disease (COVID-19) originated in China has spread around the world. The disease is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The presence of myocarditis, cardiac arrest, and acute heart failure in COVID-19 patients suggests the existence of a relationship between SARS-CoV-2 infection and cardiac disease. The Notch signalling is a major regulator of cardiovascular function and it is also implicated in several biological processes mediating viral infections. In this report we discuss the possibility to target Notch signalling to prevent SARS-CoV-2 infection and interfere with the progression of COVID-19- associated heart and lungs disease.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Agata, J" uniqKey="Agata J">J Agata</name></author><author><name sortKey="Ura, N" uniqKey="Ura N">N Ura</name></author><author><name sortKey="Yoshida, H" uniqKey="Yoshida H">H Yoshida</name></author><author><name sortKey="Shinshi, Y" uniqKey="Shinshi Y">Y Shinshi</name></author><author><name sortKey="Sasaki, H" uniqKey="Sasaki H">H Sasaki</name></author><author><name sortKey="Hyakkoku, M" uniqKey="Hyakkoku M">M Hyakkoku</name></author><author><name sortKey="Taniguchi, S" uniqKey="Taniguchi S">S Taniguchi</name></author><author><name sortKey="Shimamoto, K" uniqKey="Shimamoto K">K Shimamoto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aquila, G" uniqKey="Aquila G">G Aquila</name></author><author><name sortKey="Kostina, A" uniqKey="Kostina A">A Kostina</name></author><author><name sortKey="Vieceli Dalla Sega, F" uniqKey="Vieceli Dalla Sega F">F Vieceli Dalla Sega</name></author><author><name sortKey="Shlyakhto, E" uniqKey="Shlyakhto E">E Shlyakhto</name></author><author><name sortKey="Kostareva, A" uniqKey="Kostareva A">A Kostareva</name></author><author><name sortKey="Marracino, L" uniqKey="Marracino L">L Marracino</name></author><author><name sortKey="Ferrari, R" uniqKey="Ferrari R">R Ferrari</name></author><author><name sortKey="Rizzo, P" uniqKey="Rizzo P">P Rizzo</name></author><author><name sortKey="Malaschicheva, A" uniqKey="Malaschicheva A">A Malaschicheva</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Benvenuto, D" uniqKey="Benvenuto D">D Benvenuto</name></author><author><name sortKey="Giovanetti, M" uniqKey="Giovanetti M">M Giovanetti</name></author><author><name sortKey="Ciccozzi, A" uniqKey="Ciccozzi A">A Ciccozzi</name></author><author><name sortKey="Spoto, S" uniqKey="Spoto S">S Spoto</name></author><author><name sortKey="Angeletti, S" uniqKey="Angeletti S">S Angeletti</name></author><author><name sortKey="Ciccozzi, M" uniqKey="Ciccozzi M">M Ciccozzi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Boucher, Jm" uniqKey="Boucher J">JM Boucher</name></author><author><name sortKey="Peterson, Sm" uniqKey="Peterson S">SM Peterson</name></author><author><name sortKey="Urs, S" uniqKey="Urs S">S Urs</name></author><author><name sortKey="Zhang, C" uniqKey="Zhang C">C Zhang</name></author><author><name sortKey="Liaw, L" uniqKey="Liaw L">L Liaw</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Caolo, V" uniqKey="Caolo V">V Caolo</name></author><author><name sortKey="Schulten, Hm" uniqKey="Schulten H">HM Schulten</name></author><author><name sortKey="Zhuang, Zw" uniqKey="Zhuang Z">ZW Zhuang</name></author><author><name sortKey="Murakami, M" uniqKey="Murakami M">M Murakami</name></author><author><name sortKey="Wagenaar, A" uniqKey="Wagenaar A">A Wagenaar</name></author><author><name sortKey="Verbruggen, S" uniqKey="Verbruggen S">S Verbruggen</name></author><author><name sortKey="Molin, Dg" uniqKey="Molin D">DG Molin</name></author><author><name sortKey="Post, Mj" uniqKey="Post M">MJ Post</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carbone, M" uniqKey="Carbone M">M Carbone</name></author><author><name sortKey="Green, Jb" uniqKey="Green J">JB Green</name></author><author><name sortKey="Bucci, Em" uniqKey="Bucci E">EM Bucci</name></author><author><name sortKey="Lednicky, Jj" uniqKey="Lednicky J">JJ Lednicky</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chen, N" uniqKey="Chen N">N Chen</name></author><author><name sortKey="Zhou, M" uniqKey="Zhou M">M Zhou</name></author><author><name sortKey="Dong, X" uniqKey="Dong X">X Dong</name></author><author><name sortKey="Qu, J" uniqKey="Qu J">J Qu</name></author><author><name sortKey="Gong, F" uniqKey="Gong F">F Gong</name></author><author><name sortKey="Han, Y" uniqKey="Han Y">Y Han</name></author><author><name sortKey="Qiu, Y" uniqKey="Qiu Y">Y Qiu</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J Wang</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name></author><author><name sortKey="Wei, Y" uniqKey="Wei Y">Y Wei</name></author><author><name sortKey="Xia, J" uniqKey="Xia J">J Xia</name></author><author><name sortKey="Yu, T" uniqKey="Yu T">T Yu</name></author><author><name sortKey="Zhang, X" uniqKey="Zhang X">X Zhang</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cheng, J" uniqKey="Cheng J">J Cheng</name></author><author><name sortKey="Koenig, Sn" uniqKey="Koenig S">SN Koenig</name></author><author><name sortKey="Kuivaniemi, Hs" uniqKey="Kuivaniemi H">HS Kuivaniemi</name></author><author><name sortKey="Garg, V" uniqKey="Garg V">V Garg</name></author><author><name sortKey="Hans, Cp" uniqKey="Hans C">CP Hans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Aarpamfatm, C" uniqKey="Aarpamfatm C">C AaRPaMFaTM</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Collins, Sd" uniqKey="Collins S">SD Collins</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corrales Medina, Vf" uniqKey="Corrales Medina V">VF Corrales-Medina</name></author><author><name sortKey="Madjid, M" uniqKey="Madjid M">M Madjid</name></author><author><name sortKey="Musher, Dm" uniqKey="Musher D">DM Musher</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Danahay, H" uniqKey="Danahay H">H Danahay</name></author><author><name sortKey="Pessotti, Ad" uniqKey="Pessotti A">AD Pessotti</name></author><author><name sortKey="Coote, J" uniqKey="Coote J">J Coote</name></author><author><name sortKey="Montgomery, Be" uniqKey="Montgomery B">BE Montgomery</name></author><author><name sortKey="Xia, D" uniqKey="Xia D">D Xia</name></author><author><name sortKey="Wilson, A" uniqKey="Wilson A">A Wilson</name></author><author><name sortKey="Yang, H" uniqKey="Yang H">H Yang</name></author><author><name sortKey="Wang, Z" uniqKey="Wang Z">Z Wang</name></author><author><name sortKey="Bevan, L" uniqKey="Bevan L">L Bevan</name></author><author><name sortKey="Thomas, C" uniqKey="Thomas C">C Thomas</name></author><author><name sortKey="Petit, S" uniqKey="Petit S">S Petit</name></author><author><name sortKey="London, A" uniqKey="London A">A London</name></author><author><name sortKey="Lemotte, P" uniqKey="Lemotte P">P LeMotte</name></author><author><name sortKey="Doelemeyer, A" uniqKey="Doelemeyer A">A Doelemeyer</name></author><author><name sortKey="Velez Reyes, Gl" uniqKey="Velez Reyes G">GL Vélez-Reyes</name></author><author><name sortKey="Bernasconi, P" uniqKey="Bernasconi P">P Bernasconi</name></author><author><name sortKey="Fryer, Cj" uniqKey="Fryer C">CJ Fryer</name></author><author><name sortKey="Edwards, M" uniqKey="Edwards M">M Edwards</name></author><author><name sortKey="Capodieci, P" uniqKey="Capodieci P">P Capodieci</name></author><author><name sortKey="Chen, A" uniqKey="Chen A">A Chen</name></author><author><name sortKey="Hild, M" uniqKey="Hild M">M Hild</name></author><author><name sortKey="Jaffe, Ab" uniqKey="Jaffe A">AB Jaffe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="David, Eg" uniqKey="David E">EG David</name></author><author><name sortKey="Gwendolyn, Mj" uniqKey="Gwendolyn M">MJ Gwendolyn</name></author><author><name sortKey="Mehdi, B" uniqKey="Mehdi B">B Mehdi</name></author><author><name sortKey="Jiewei, X" uniqKey="Jiewei X">X Jiewei</name></author><author><name sortKey="Kirsten, O" uniqKey="Kirsten O">O Kirsten</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Doberstein, K" uniqKey="Doberstein K">K Doberstein</name></author><author><name sortKey="Steinmeyer, N" uniqKey="Steinmeyer N">N Steinmeyer</name></author><author><name sortKey="Hartmetz, Ak" uniqKey="Hartmetz A">AK Hartmetz</name></author><author><name sortKey="Eberhardt, W" uniqKey="Eberhardt W">W Eberhardt</name></author><author><name sortKey="Mittelbronn, M" uniqKey="Mittelbronn M">M Mittelbronn</name></author><author><name sortKey="Harter, Pn" uniqKey="Harter P">PN Harter</name></author><author><name sortKey="Juengel, E" uniqKey="Juengel E">E Juengel</name></author><author><name sortKey="Blaheta, R" uniqKey="Blaheta R">R Blaheta</name></author><author><name sortKey="Pfeilschifter, J" uniqKey="Pfeilschifter J">J Pfeilschifter</name></author><author><name sortKey="Gutwein, P" uniqKey="Gutwein P">P Gutwein</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fang, L" uniqKey="Fang L">L Fang</name></author><author><name sortKey="Karakiulakis, G" uniqKey="Karakiulakis G">G Karakiulakis</name></author><author><name sortKey="Roth, M" uniqKey="Roth M">M Roth</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Ferrari, R" uniqKey="Ferrari R">R Ferrari</name></author><author><name sortKey="Rizzo, P" uniqKey="Rizzo P">P Rizzo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fortini, F" uniqKey="Fortini F">F Fortini</name></author><author><name sortKey="Vieceli Dalla Sega, F" uniqKey="Vieceli Dalla Sega F">F Vieceli Dalla Sega</name></author><author><name sortKey="Caliceti, C" uniqKey="Caliceti C">C Caliceti</name></author><author><name sortKey="Lambertini, E" uniqKey="Lambertini E">E Lambertini</name></author><author><name sortKey="Pannuti, A" uniqKey="Pannuti A">A Pannuti</name></author><author><name sortKey="Peiffer, Ds" uniqKey="Peiffer D">DS Peiffer</name></author><author><name sortKey="Balla, C" uniqKey="Balla C">C Balla</name></author><author><name sortKey="Rizzo, P" uniqKey="Rizzo P">P Rizzo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guan, Wj" uniqKey="Guan W">WJ Guan</name></author><author><name sortKey="Ni, Zy" uniqKey="Ni Z">ZY Ni</name></author><author><name sortKey="Hu, Y" uniqKey="Hu Y">Y Hu</name></author><author><name sortKey="Liang, Wh" uniqKey="Liang W">WH Liang</name></author><author><name sortKey="Ou, Cq" uniqKey="Ou C">CQ Ou</name></author><author><name sortKey="He, Jx" uniqKey="He J">JX He</name></author><author><name sortKey="Liu, L" uniqKey="Liu L">L Liu</name></author><author><name sortKey="Shan, H" uniqKey="Shan H">H Shan</name></author><author><name sortKey="Lei, Cl" uniqKey="Lei C">CL Lei</name></author><author><name sortKey="Hui, Dsc" uniqKey="Hui D">DSC Hui</name></author><author><name sortKey="Du, B" uniqKey="Du B">B Du</name></author><author><name sortKey="Li, Lj" uniqKey="Li L">LJ Li</name></author><author><name sortKey="Zeng, G" uniqKey="Zeng G">G Zeng</name></author><author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name></author><author><name sortKey="Chen, Rc" uniqKey="Chen R">RC Chen</name></author><author><name sortKey="Tang, Cl" uniqKey="Tang C">CL Tang</name></author><author><name sortKey="Wang, T" uniqKey="Wang T">T Wang</name></author><author><name sortKey="Chen, Py" uniqKey="Chen P">PY Chen</name></author><author><name sortKey="Xiang, J" uniqKey="Xiang J">J Xiang</name></author><author><name sortKey="Li, Sy" uniqKey="Li S">SY Li</name></author><author><name sortKey="Wang, Jl" uniqKey="Wang J">JL Wang</name></author><author><name sortKey="Liang, Zj" uniqKey="Liang Z">ZJ Liang</name></author><author><name sortKey="Peng, Yx" uniqKey="Peng Y">YX Peng</name></author><author><name sortKey="Wei, L" uniqKey="Wei L">L Wei</name></author><author><name sortKey="Liu, Y" uniqKey="Liu Y">Y Liu</name></author><author><name sortKey="Hu, Yh" uniqKey="Hu Y">YH Hu</name></author><author><name sortKey="Peng, P" uniqKey="Peng P">P Peng</name></author><author><name sortKey="Wang, Jm" uniqKey="Wang J">JM Wang</name></author><author><name sortKey="Liu, Jy" uniqKey="Liu J">JY Liu</name></author><author><name sortKey="Chen, Z" uniqKey="Chen Z">Z Chen</name></author><author><name sortKey="Li, G" uniqKey="Li G">G Li</name></author><author><name sortKey="Zheng, Zj" uniqKey="Zheng Z">ZJ Zheng</name></author><author><name sortKey="Qiu, Sq" uniqKey="Qiu S">SQ Qiu</name></author><author><name sortKey="Luo, J" uniqKey="Luo J">J Luo</name></author><author><name sortKey="Ye, Cj" uniqKey="Ye C">CJ Ye</name></author><author><name sortKey="Zhu, Sy" uniqKey="Zhu S">SY Zhu</name></author><author><name sortKey="Zhong, Ns" uniqKey="Zhong N">NS Zhong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Gude, N" uniqKey="Gude N">N Gude</name></author><author><name sortKey="Joyo, E" uniqKey="Joyo E">E Joyo</name></author><author><name sortKey="Toko, H" uniqKey="Toko H">H Toko</name></author><author><name sortKey="Quijada, P" uniqKey="Quijada P">P Quijada</name></author><author><name sortKey="Villanueva, M" uniqKey="Villanueva M">M Villanueva</name></author><author><name sortKey="Hariharan, N" uniqKey="Hariharan N">N Hariharan</name></author><author><name sortKey="Sacchi, V" uniqKey="Sacchi V">V Sacchi</name></author><author><name sortKey="Truffa, S" uniqKey="Truffa S">S Truffa</name></author><author><name sortKey="Joyo, A" uniqKey="Joyo A">A Joyo</name></author><author><name sortKey="Voelkers, M" uniqKey="Voelkers M">M Voelkers</name></author><author><name sortKey="Alvarez, R" uniqKey="Alvarez R">R Alvarez</name></author><author><name sortKey="Sussman, Ma" uniqKey="Sussman M">MA Sussman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hildebrand, D" uniqKey="Hildebrand D">D Hildebrand</name></author><author><name sortKey="Uhle, F" uniqKey="Uhle F">F Uhle</name></author><author><name sortKey="Sahin, D" uniqKey="Sahin D">D Sahin</name></author><author><name sortKey="Krauser, U" uniqKey="Krauser U">U Krauser</name></author><author><name sortKey="Weigand, Ma" uniqKey="Weigand M">MA Weigand</name></author><author><name sortKey="Heeg, K" uniqKey="Heeg K">K Heeg</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hoffmann, M" uniqKey="Hoffmann M">M Hoffmann</name></author><author><name sortKey="Kleine Weber, H" uniqKey="Kleine Weber H">H Kleine-Weber</name></author><author><name sortKey="Schroeder, S" uniqKey="Schroeder S">S Schroeder</name></author><author><name sortKey="Kruger, N" uniqKey="Kruger N">N Krüger</name></author><author><name sortKey="Herrler, T" uniqKey="Herrler T">T Herrler</name></author><author><name sortKey="Erichsen, S" uniqKey="Erichsen S">S Erichsen</name></author><author><name sortKey="Schiergens, Ts" uniqKey="Schiergens T">TS Schiergens</name></author><author><name sortKey="Herrler, G" uniqKey="Herrler G">G Herrler</name></author><author><name sortKey="Wu, Nh" uniqKey="Wu N">NH Wu</name></author><author><name sortKey="Nitsche, A" uniqKey="Nitsche A">A Nitsche</name></author><author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Müller</name></author><author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name></author><author><name sortKey="Pohlmann, S" uniqKey="Pohlmann S">S Pöhlmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, C" uniqKey="Huang C">C Huang</name></author><author><name sortKey="Wang, Y" uniqKey="Wang Y">Y Wang</name></author><author><name sortKey="Li, X" uniqKey="Li X">X Li</name></author><author><name sortKey="Ren, L" uniqKey="Ren L">L Ren</name></author><author><name sortKey="Zhao, J" uniqKey="Zhao J">J Zhao</name></author><author><name sortKey="Hu, Y" uniqKey="Hu Y">Y Hu</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L Zhang</name></author><author><name sortKey="Fan, G" uniqKey="Fan G">G Fan</name></author><author><name sortKey="Xu, J" uniqKey="Xu J">J Xu</name></author><author><name sortKey="Gu, X" uniqKey="Gu X">X Gu</name></author><author><name sortKey="Cheng, Z" uniqKey="Cheng Z">Z Cheng</name></author><author><name sortKey="Yu, T" uniqKey="Yu T">T Yu</name></author><author><name sortKey="Xia, J" uniqKey="Xia J">J Xia</name></author><author><name sortKey="Wei, Y" uniqKey="Wei Y">Y Wei</name></author><author><name sortKey="Wu, W" uniqKey="Wu W">W Wu</name></author><author><name sortKey="Xie, X" uniqKey="Xie X">X Xie</name></author><author><name sortKey="Yin, W" uniqKey="Yin W">W Yin</name></author><author><name sortKey="Li, H" uniqKey="Li H">H Li</name></author><author><name sortKey="Liu, M" uniqKey="Liu M">M Liu</name></author><author><name sortKey="Xiao, Y" uniqKey="Xiao Y">Y Xiao</name></author><author><name sortKey="Gao, H" uniqKey="Gao H">H Gao</name></author><author><name sortKey="Guo, L" uniqKey="Guo L">L Guo</name></author><author><name sortKey="Xie, J" uniqKey="Xie J">J Xie</name></author><author><name sortKey="Wang, G" uniqKey="Wang G">G Wang</name></author><author><name sortKey="Jiang, R" uniqKey="Jiang R">R Jiang</name></author><author><name sortKey="Gao, Z" uniqKey="Gao Z">Z Gao</name></author><author><name sortKey="Jin, Q" uniqKey="Jin Q">Q Jin</name></author><author><name sortKey="Wang, J" uniqKey="Wang J">J Wang</name></author><author><name sortKey="Cao, B" uniqKey="Cao B">B Cao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ito, T" uniqKey="Ito T">T Ito</name></author><author><name sortKey="Allen, Rm" uniqKey="Allen R">RM Allen</name></author><author><name sortKey="Carson, Wf" uniqKey="Carson W">WF Carson</name></author><author><name sortKey="Schaller, M" uniqKey="Schaller M">M Schaller</name></author><author><name sortKey="Cavassani, Ka" uniqKey="Cavassani K">KA Cavassani</name></author><author><name sortKey="Hogaboam, Cm" uniqKey="Hogaboam C">CM Hogaboam</name></author><author><name sortKey="Lukacs, Nw" uniqKey="Lukacs N">NW Lukacs</name></author><author><name sortKey="Matsukawa, A" uniqKey="Matsukawa A">A Matsukawa</name></author><author><name sortKey="Kunkel, Sl" uniqKey="Kunkel S">SL Kunkel</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kyula, Jn" uniqKey="Kyula J">JN Kyula</name></author><author><name sortKey="Van Schaeybroeck, S" uniqKey="Van Schaeybroeck S">S Van Schaeybroeck</name></author><author><name sortKey="Doherty, J" uniqKey="Doherty J">J Doherty</name></author><author><name sortKey="Fenning, Cs" uniqKey="Fenning C">CS Fenning</name></author><author><name sortKey="Longley, Db" uniqKey="Longley D">DB Longley</name></author><author><name sortKey="Johnston, Pg" uniqKey="Johnston P">PG Johnston</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lambert, Dw" uniqKey="Lambert D">DW Lambert</name></author><author><name sortKey="Yarski, M" uniqKey="Yarski M">M Yarski</name></author><author><name sortKey="Warner, Fj" uniqKey="Warner F">FJ Warner</name></author><author><name sortKey="Thornhill, P" uniqKey="Thornhill P">P Thornhill</name></author><author><name sortKey="Parkin, Et" uniqKey="Parkin E">ET Parkin</name></author><author><name sortKey="Smith, Ai" uniqKey="Smith A">AI Smith</name></author><author><name sortKey="Hooper, Nm" uniqKey="Hooper N">NM Hooper</name></author><author><name sortKey="Turner, Aj" uniqKey="Turner A">AJ Turner</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lei, C" uniqKey="Lei C">C Lei</name></author><author><name sortKey="Fu, W" uniqKey="Fu W">W Fu</name></author><author><name sortKey="Qian, K" uniqKey="Qian K">K Qian</name></author><author><name sortKey="Li, T" uniqKey="Li T">T Li</name></author><author><name sortKey="Zhang, S" uniqKey="Zhang S">S Zhang</name></author><author><name sortKey="Ding, M" uniqKey="Ding M">M Ding</name></author><author><name sortKey="Hu, S" uniqKey="Hu S">S Hu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lukacs, Nw" uniqKey="Lukacs N">NW Lukacs</name></author><author><name sortKey="Smit, Jj" uniqKey="Smit J">JJ Smit</name></author><author><name sortKey="Schaller, Ma" uniqKey="Schaller M">MA Schaller</name></author><author><name sortKey="Lindell, Dm" uniqKey="Lindell D">DM Lindell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Molano, Fd" uniqKey="Molano F">FD Molano</name></author><author><name sortKey="Arevalo Rodriguez, I" uniqKey="Arevalo Rodriguez I">I Arevalo-Rodriguez</name></author><author><name sortKey="Roque I Figuls, M" uniqKey="Roque I Figuls M">M Roqué i Figuls</name></author><author><name sortKey="Montero Oleas, N" uniqKey="Montero Oleas N">N Montero Oleas</name></author><author><name sortKey="Nuvials, X" uniqKey="Nuvials X">X Nuvials</name></author><author><name sortKey="Zamora, J" uniqKey="Zamora J">J Zamora</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Osborne, Ba" uniqKey="Osborne B">BA Osborne</name></author><author><name sortKey="Minter, Lm" uniqKey="Minter L">LM Minter</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Park, Js" uniqKey="Park J">JS Park</name></author><author><name sortKey="Kim, Sh" uniqKey="Kim S">SH Kim</name></author><author><name sortKey="Kim, K" uniqKey="Kim K">K Kim</name></author><author><name sortKey="Jin, Ch" uniqKey="Jin C">CH Jin</name></author><author><name sortKey="Choi, Ky" uniqKey="Choi K">KY Choi</name></author><author><name sortKey="Jang, J" uniqKey="Jang J">J Jang</name></author><author><name sortKey="Choi, Y" uniqKey="Choi Y">Y Choi</name></author><author><name sortKey="Gwon, Ar" uniqKey="Gwon A">AR Gwon</name></author><author><name sortKey="Baik, Sh" uniqKey="Baik S">SH Baik</name></author><author><name sortKey="Yun, Uj" uniqKey="Yun U">UJ Yun</name></author><author><name sortKey="Chae, Sy" uniqKey="Chae S">SY Chae</name></author><author><name sortKey="Lee, S" uniqKey="Lee S">S Lee</name></author><author><name sortKey="Kang, Ym" uniqKey="Kang Y">YM Kang</name></author><author><name sortKey="Lee, Kc" uniqKey="Lee K">KC Lee</name></author><author><name sortKey="Arumugam, Tv" uniqKey="Arumugam T">TV Arumugam</name></author><author><name sortKey="Mattson, Mp" uniqKey="Mattson M">MP Mattson</name></author><author><name sortKey="Park, Jh" uniqKey="Park J">JH Park</name></author><author><name sortKey="Jo, Dg" uniqKey="Jo D">DG Jo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Patel, Vb" uniqKey="Patel V">VB Patel</name></author><author><name sortKey="Clarke, N" uniqKey="Clarke N">N Clarke</name></author><author><name sortKey="Wang, Z" uniqKey="Wang Z">Z Wang</name></author><author><name sortKey="Fan, D" uniqKey="Fan D">D Fan</name></author><author><name sortKey="Parajuli, N" uniqKey="Parajuli N">N Parajuli</name></author><author><name sortKey="Basu, R" uniqKey="Basu R">R Basu</name></author><author><name sortKey="Putko, B" uniqKey="Putko B">B Putko</name></author><author><name sortKey="Kassiri, Z" uniqKey="Kassiri Z">Z Kassiri</name></author><author><name sortKey="Turner, Aj" uniqKey="Turner A">AJ Turner</name></author><author><name sortKey="Oudit, Gy" uniqKey="Oudit G">GY Oudit</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Paules, Ci" uniqKey="Paules C">CI Paules</name></author><author><name sortKey="Marston, Hd" uniqKey="Marston H">HD Marston</name></author><author><name sortKey="Fauci, As" uniqKey="Fauci A">AS Fauci</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Pei, H" uniqKey="Pei H">H Pei</name></author><author><name sortKey="Yu, Q" uniqKey="Yu Q">Q Yu</name></author><author><name sortKey="Xue, Q" uniqKey="Xue Q">Q Xue</name></author><author><name sortKey="Guo, Y" uniqKey="Guo Y">Y Guo</name></author><author><name sortKey="Sun, L" uniqKey="Sun L">L Sun</name></author><author><name sortKey="Hong, Z" uniqKey="Hong Z">Z Hong</name></author><author><name sortKey="Han, H" uniqKey="Han H">H Han</name></author><author><name sortKey="Gao, E" uniqKey="Gao E">E Gao</name></author><author><name sortKey="Qu, Y" uniqKey="Qu Y">Y Qu</name></author><author><name sortKey="Tao, L" uniqKey="Tao L">L Tao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Penninkilampi, R" uniqKey="Penninkilampi R">R Penninkilampi</name></author><author><name sortKey="Brothers, Hm" uniqKey="Brothers H">HM Brothers</name></author><author><name sortKey="Eslick, Gd" uniqKey="Eslick G">GD Eslick</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qin, C" uniqKey="Qin C">C Qin</name></author><author><name sortKey="Zhou, L" uniqKey="Zhou L">L Zhou</name></author><author><name sortKey="Hu, Z" uniqKey="Hu Z">Z Hu</name></author><author><name sortKey="Zhang, S" uniqKey="Zhang S">S Zhang</name></author><author><name sortKey="Yang, S" uniqKey="Yang S">S Yang</name></author><author><name sortKey="Tao, Y" uniqKey="Tao Y">Y Tao</name></author><author><name sortKey="Xie, C" uniqKey="Xie C">C Xie</name></author><author><name sortKey="Ma, K" uniqKey="Ma K">K Ma</name></author><author><name sortKey="Shang, K" uniqKey="Shang K">K Shang</name></author><author><name sortKey="Wang, W" uniqKey="Wang W">W Wang</name></author><author><name sortKey="Tian, Ds" uniqKey="Tian D">DS Tian</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qin, L" uniqKey="Qin L">L Qin</name></author><author><name sortKey="Qiu, Kz" uniqKey="Qiu K">KZ Qiu</name></author><author><name sortKey="Hu, Cp" uniqKey="Hu C">CP Hu</name></author><author><name sortKey="Wu, Gj" uniqKey="Wu G">GJ Wu</name></author><author><name sortKey="Wang, Ll" uniqKey="Wang L">LL Wang</name></author><author><name sortKey="Tan, Yr" uniqKey="Tan Y">YR Tan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Qiu, H" uniqKey="Qiu H">H Qiu</name></author><author><name sortKey="Tang, X" uniqKey="Tang X">X Tang</name></author><author><name sortKey="Ma, J" uniqKey="Ma J">J Ma</name></author><author><name sortKey="Shaverdashvili, K" uniqKey="Shaverdashvili K">K Shaverdashvili</name></author><author><name sortKey="Zhang, K" uniqKey="Zhang K">K Zhang</name></author><author><name sortKey="Bedogni, B" uniqKey="Bedogni B">B Bedogni</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Radojcic, V" uniqKey="Radojcic V">V Radojcic</name></author><author><name sortKey="Maillard, I" uniqKey="Maillard I">I Maillard</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rapezzi, C" uniqKey="Rapezzi C">C Rapezzi</name></author><author><name sortKey="Ferrari, R" uniqKey="Ferrari R">R Ferrari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ren, J" uniqKey="Ren J">J Ren</name></author><author><name sortKey="Nie, Y" uniqKey="Nie Y">Y Nie</name></author><author><name sortKey="Lv, M" uniqKey="Lv M">M Lv</name></author><author><name sortKey="Shen, S" uniqKey="Shen S">S Shen</name></author><author><name sortKey="Tang, R" uniqKey="Tang R">R Tang</name></author><author><name sortKey="Xu, Y" uniqKey="Xu Y">Y Xu</name></author><author><name sortKey="Hou, Y" uniqKey="Hou Y">Y Hou</name></author><author><name sortKey="Zhao, S" uniqKey="Zhao S">S Zhao</name></author><author><name sortKey="Wang, T" uniqKey="Wang T">T Wang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rizzo, P" uniqKey="Rizzo P">P Rizzo</name></author><author><name sortKey="Miele, L" uniqKey="Miele L">L Miele</name></author><author><name sortKey="Ferrari, R" uniqKey="Ferrari R">R Ferrari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ruan, Q" uniqKey="Ruan Q">Q Ruan</name></author><author><name sortKey="Yang, K" uniqKey="Yang K">K Yang</name></author><author><name sortKey="Wang, W" uniqKey="Wang W">W Wang</name></author><author><name sortKey="Jiang, L" uniqKey="Jiang L">L Jiang</name></author><author><name sortKey="Song, J" uniqKey="Song J">J Song</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schmieder, Re" uniqKey="Schmieder R">RE Schmieder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schneider, Cs" uniqKey="Schneider C">CS Schneider</name></author><author><name sortKey="Xu, Q" uniqKey="Xu Q">Q Xu</name></author><author><name sortKey="Boylan, Nj" uniqKey="Boylan N">NJ Boylan</name></author><author><name sortKey="Chisholm, J" uniqKey="Chisholm J">J Chisholm</name></author><author><name sortKey="Tang, Bc" uniqKey="Tang B">BC Tang</name></author><author><name sortKey="Schuster, Bs" uniqKey="Schuster B">BS Schuster</name></author><author><name sortKey="Henning, A" uniqKey="Henning A">A Henning</name></author><author><name sortKey="Ensign, Lm" uniqKey="Ensign L">LM Ensign</name></author><author><name sortKey="Lee, E" uniqKey="Lee E">E Lee</name></author><author><name sortKey="Adstamongkonkul, P" uniqKey="Adstamongkonkul P">P Adstamongkonkul</name></author><author><name sortKey="Simons, Bw" uniqKey="Simons B">BW Simons</name></author><author><name sortKey="Wang, Ss" uniqKey="Wang S">SS Wang</name></author><author><name sortKey="Gong, X" uniqKey="Gong X">X Gong</name></author><author><name sortKey="Yu, T" uniqKey="Yu T">T Yu</name></author><author><name sortKey="Boyle, Mp" uniqKey="Boyle M">MP Boyle</name></author><author><name sortKey="Suk, Js" uniqKey="Suk J">JS Suk</name></author><author><name sortKey="Hanes, J" uniqKey="Hanes J">J Hanes</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Schoeman, D" uniqKey="Schoeman D">D Schoeman</name></author><author><name sortKey="Fielding, Bc" uniqKey="Fielding B">BC Fielding</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shiryaev, Sa" uniqKey="Shiryaev S">SA Shiryaev</name></author><author><name sortKey="Remacle, Ag" uniqKey="Remacle A">AG Remacle</name></author><author><name sortKey="Ratnikov, Bi" uniqKey="Ratnikov B">BI Ratnikov</name></author><author><name sortKey="Nelson, Na" uniqKey="Nelson N">NA Nelson</name></author><author><name sortKey="Savinov, Ay" uniqKey="Savinov A">AY Savinov</name></author><author><name sortKey="Wei, G" uniqKey="Wei G">G Wei</name></author><author><name sortKey="Bottini, M" uniqKey="Bottini M">M Bottini</name></author><author><name sortKey="Rega, Mf" uniqKey="Rega M">MF Rega</name></author><author><name sortKey="Parent, A" uniqKey="Parent A">A Parent</name></author><author><name sortKey="Desjardins, R" uniqKey="Desjardins R">R Desjardins</name></author><author><name sortKey="Fugere, M" uniqKey="Fugere M">M Fugere</name></author><author><name sortKey="Day, R" uniqKey="Day R">R Day</name></author><author><name sortKey="Sabet, M" uniqKey="Sabet M">M Sabet</name></author><author><name sortKey="Pellecchia, M" uniqKey="Pellecchia M">M Pellecchia</name></author><author><name sortKey="Liddington, Rc" uniqKey="Liddington R">RC Liddington</name></author><author><name sortKey="Smith, Jw" uniqKey="Smith J">JW Smith</name></author><author><name sortKey="Mustelin, T" uniqKey="Mustelin T">T Mustelin</name></author><author><name sortKey="Guiney, Dg" uniqKey="Guiney D">DG Guiney</name></author><author><name sortKey="Lebl, M" uniqKey="Lebl M">M Lebl</name></author><author><name sortKey="Strongin, Ay" uniqKey="Strongin A">AY Strongin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tian, S" uniqKey="Tian S">S Tian</name></author><author><name sortKey="Hu, W" uniqKey="Hu W">W Hu</name></author><author><name sortKey="Niu, L" uniqKey="Niu L">L Niu</name></author><author><name sortKey="Liu, H" uniqKey="Liu H">H Liu</name></author><author><name sortKey="Xu, H" uniqKey="Xu H">H Xu</name></author><author><name sortKey="Xiao, Sy" uniqKey="Xiao S">SY Xiao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Vieceli Dalla Sega, F" uniqKey="Vieceli Dalla Sega F">F Vieceli Dalla Sega</name></author><author><name sortKey="Fortini, F" uniqKey="Fortini F">F Fortini</name></author><author><name sortKey="Aquila, G" uniqKey="Aquila G">G Aquila</name></author><author><name sortKey="Campo, G" uniqKey="Campo G">G Campo</name></author><author><name sortKey="Vaccarezza, M" uniqKey="Vaccarezza M">M Vaccarezza</name></author><author><name sortKey="Rizzo, P" uniqKey="Rizzo P">P Rizzo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Walls, Ac" uniqKey="Walls A">AC Walls</name></author><author><name sortKey="Park, Yj" uniqKey="Park Y">YJ Park</name></author><author><name sortKey="Tortorici, Ma" uniqKey="Tortorici M">MA Tortorici</name></author><author><name sortKey="Wall, A" uniqKey="Wall A">A Wall</name></author><author><name sortKey="Mcguire, At" uniqKey="Mcguire A">AT McGuire</name></author><author><name sortKey="Veesler, D" uniqKey="Veesler D">D Veesler</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, D" uniqKey="Wang D">D Wang</name></author><author><name sortKey="Hu, B" uniqKey="Hu B">B Hu</name></author><author><name sortKey="Hu, C" uniqKey="Hu C">C Hu</name></author><author><name sortKey="Zhu, F" uniqKey="Zhu F">F Zhu</name></author><author><name sortKey="Liu, X" uniqKey="Liu X">X Liu</name></author><author><name sortKey="Zhang, J" uniqKey="Zhang J">J Zhang</name></author><author><name sortKey="Wang, B" uniqKey="Wang B">B Wang</name></author><author><name sortKey="Xiang, H" uniqKey="Xiang H">H Xiang</name></author><author><name sortKey="Cheng, Z" uniqKey="Cheng Z">Z Cheng</name></author><author><name sortKey="Xiong, Y" uniqKey="Xiong Y">Y Xiong</name></author><author><name sortKey="Zhao, Y" uniqKey="Zhao Y">Y Zhao</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X Wang</name></author><author><name sortKey="Peng, Z" uniqKey="Peng Z">Z Peng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wongchana, W" uniqKey="Wongchana W">W Wongchana</name></author><author><name sortKey="Palaga, T" uniqKey="Palaga T">T Palaga</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zheng, Yy" uniqKey="Zheng Y">YY Zheng</name></author><author><name sortKey="Ma, Yt" uniqKey="Ma Y">YT Ma</name></author><author><name sortKey="Zhang, Jy" uniqKey="Zhang J">JY Zhang</name></author><author><name sortKey="Xie, X" uniqKey="Xie X">X Xie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, P" uniqKey="Zhou P">P Zhou</name></author><author><name sortKey="Yang, Xl" uniqKey="Yang X">XL Yang</name></author><author><name sortKey="Wang, Xg" uniqKey="Wang X">XG Wang</name></author><author><name sortKey="Hu, B" uniqKey="Hu B">B Hu</name></author><author><name sortKey="Zhang, L" uniqKey="Zhang L">L Zhang</name></author><author><name sortKey="Zhang, W" uniqKey="Zhang W">W Zhang</name></author><author><name sortKey="Si, Hr" uniqKey="Si H">HR Si</name></author><author><name sortKey="Zhu, Y" uniqKey="Zhu Y">Y Zhu</name></author><author><name sortKey="Li, B" uniqKey="Li B">B Li</name></author><author><name sortKey="Huang, Cl" uniqKey="Huang C">CL Huang</name></author><author><name sortKey="Chen, Hd" uniqKey="Chen H">HD Chen</name></author><author><name sortKey="Chen, J" uniqKey="Chen J">J Chen</name></author><author><name sortKey="Luo, Y" uniqKey="Luo Y">Y Luo</name></author><author><name sortKey="Guo, H" uniqKey="Guo H">H Guo</name></author><author><name sortKey="Jiang, Rd" uniqKey="Jiang R">RD Jiang</name></author><author><name sortKey="Liu, Mq" uniqKey="Liu M">MQ Liu</name></author><author><name sortKey="Chen, Y" uniqKey="Chen Y">Y Chen</name></author><author><name sortKey="Shen, Xr" uniqKey="Shen X">XR Shen</name></author><author><name sortKey="Wang, X" uniqKey="Wang X">X Wang</name></author><author><name sortKey="Zheng, Xs" uniqKey="Zheng X">XS Zheng</name></author><author><name sortKey="Zhao, K" uniqKey="Zhao K">K Zhao</name></author><author><name sortKey="Chen, Qj" uniqKey="Chen Q">QJ Chen</name></author><author><name sortKey="Deng, F" uniqKey="Deng F">F Deng</name></author><author><name sortKey="Liu, Ll" uniqKey="Liu L">LL Liu</name></author><author><name sortKey="Yan, B" uniqKey="Yan B">B Yan</name></author><author><name sortKey="Zhan, Fx" uniqKey="Zhan F">FX Zhan</name></author><author><name sortKey="Wang, Yy" uniqKey="Wang Y">YY Wang</name></author><author><name sortKey="Xiao, Gf" uniqKey="Xiao G">GF Xiao</name></author><author><name sortKey="Shi, Zl" uniqKey="Shi Z">ZL Shi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhu, N" uniqKey="Zhu N">N Zhu</name></author><author><name sortKey="Zhang, D" uniqKey="Zhang D">D Zhang</name></author><author><name sortKey="Wang, W" uniqKey="Wang W">W Wang</name></author><author><name sortKey="Li, X" uniqKey="Li X">X Li</name></author><author><name sortKey="Yang, B" uniqKey="Yang B">B Yang</name></author><author><name sortKey="Song, J" uniqKey="Song J">J Song</name></author><author><name sortKey="Zhao, X" uniqKey="Zhao X">X Zhao</name></author><author><name sortKey="Huang, B" uniqKey="Huang B">B Huang</name></author><author><name sortKey="Shi, W" uniqKey="Shi W">W Shi</name></author><author><name sortKey="Lu, R" uniqKey="Lu R">R Lu</name></author><author><name sortKey="Niu, P" uniqKey="Niu P">P Niu</name></author><author><name sortKey="Zhan, F" uniqKey="Zhan F">F Zhan</name></author><author><name sortKey="Ma, X" uniqKey="Ma X">X Ma</name></author><author><name sortKey="Wang, D" uniqKey="Wang D">D Wang</name></author><author><name sortKey="Xu, W" uniqKey="Xu W">W Xu</name></author><author><name sortKey="Wu, G" uniqKey="Wu G">G Wu</name></author><author><name sortKey="Gao, Gf" uniqKey="Gao G">GF Gao</name></author><author><name sortKey="Tan, W" uniqKey="Tan W">W Tan</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="editorial"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Basic Res Cardiol</journal-id><journal-id journal-id-type="iso-abbrev">Basic Res. Cardiol</journal-id><journal-title-group><journal-title>Basic Research in Cardiology</journal-title></journal-title-group><issn pub-type="ppub">0300-8428</issn><issn pub-type="epub">1435-1803</issn><publisher><publisher-name>Springer Berlin Heidelberg</publisher-name><publisher-loc>Berlin/Heidelberg</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32274570</article-id><article-id pub-id-type="pmc">7144545</article-id><article-id pub-id-type="publisher-id">791</article-id><article-id pub-id-type="doi">10.1007/s00395-020-0791-5</article-id><article-categories><subj-group subj-group-type="heading"><subject>Editorial</subject></subj-group></article-categories><title-group><article-title>COVID-19 in the heart and the lungs: could we “Notch” the inflammatory storm?</article-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">http://orcid.org/0000-0001-7174-9674</contrib-id><name><surname>Rizzo</surname><given-names>Paola</given-names></name><address><email>rzzpla@unife.it</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Vieceli Dalla Sega</surname><given-names>Francesco</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Fortini</surname><given-names>Francesca</given-names></name><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name><surname>Marracino</surname><given-names>Luisa</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Rapezzi</surname><given-names>Claudio</given-names></name><xref ref-type="aff" rid="Aff2">2</xref><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name><surname>Ferrari</surname><given-names>Roberto</given-names></name><xref ref-type="aff" rid="Aff2">2</xref><xref ref-type="aff" rid="Aff3">3</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1757 2064</institution-id><institution-id institution-id-type="GRID">grid.8484.0</institution-id><institution>Department of Morphology, Surgery and Experimental Medicine and Laboratory for Technologies of Advanced Therapies (LTTA),</institution><institution>University of Ferrara,</institution></institution-wrap>Ferrara, Italy</aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1785 1274</institution-id><institution-id institution-id-type="GRID">grid.417010.3</institution-id><institution>Maria Cecilia Hospital, GVM Care & Research,</institution></institution-wrap>Cotignola, Italy</aff><aff id="Aff3"><label>3</label><institution-wrap><institution-id institution-id-type="GRID">grid.416315.4</institution-id><institution>Cardiovascular Center,</institution><institution>University Hospital of Cona,</institution></institution-wrap>Ferrara, Italy</aff></contrib-group><pub-date pub-type="epub"><day>9</day><month>4</month><year>2020</year></pub-date><pub-date pub-type="ppub"><year>2020</year></pub-date><volume>115</volume><issue>3</issue><elocation-id>31</elocation-id><history><date date-type="received"><day>21</day><month>3</month><year>2020</year></date><date date-type="accepted"><day>30</day><month>3</month><year>2020</year></date></history><permissions><copyright-statement>© Springer-Verlag GmbH Germany, part of Springer Nature 2020</copyright-statement><license><license-p>This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.</license-p></license></permissions><abstract id="Abs1"><p id="Par1">From January 2020, coronavirus disease (COVID-19) originated in China has spread around the world. The disease is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The presence of myocarditis, cardiac arrest, and acute heart failure in COVID-19 patients suggests the existence of a relationship between SARS-CoV-2 infection and cardiac disease. The Notch signalling is a major regulator of cardiovascular function and it is also implicated in several biological processes mediating viral infections. In this report we discuss the possibility to target Notch signalling to prevent SARS-CoV-2 infection and interfere with the progression of COVID-19- associated heart and lungs disease.</p></abstract><kwd-group xml:lang="en"><title>Keywords</title><kwd>Coronavirus disease</kwd><kwd>COVID-19</kwd><kwd>Cardiovascular disease</kwd><kwd>Angiotensin-converting enzyme 2</kwd><kwd>Furin</kwd><kwd>ADAM17</kwd><kwd>Notch</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© Springer-Verlag GmbH Germany, part of Springer Nature 2020</meta-value></custom-meta></custom-meta-group></article-meta></front><body><sec id="Sec2"><title>On COVID-19 and the heart</title><p id="Par2">From January 2020, coronavirus disease (COVID-19) has spread fast from China, mainly to Southwest Asia and Europe, especially to Italy, and it is now found everywhere around the world. The disease is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the seventh member of the coronavirus family which infects humans and to which Middle East Respiratory Syndrome Coronavirus (MERS)-CoV and SARS-CoV also belong [<xref ref-type="bibr" rid="CR55">55</xref>]. The classical clinical picture of COVID-19 is that of a flu-like syndrome of mild severity in most cases, but in 15% of cases it is complicated by interstitial pneumonia and a variable degree of respiratory failure [<xref ref-type="bibr" rid="CR40">40</xref>]. The underlying pathological changes, responsible for the respiratory failure, have been characterised in two patients who underwent lung lobotomies for lung adenocarcinoma and were retrospectively found to be COVID-19 positive [<xref ref-type="bibr" rid="CR6">6</xref>, <xref ref-type="bibr" rid="CR48">48</xref>]. Among COVID-19-positive patients, there are those that consult the doctor for heart symptoms, such as palpitations or chest pain rather than respiratory problems [<xref ref-type="bibr" rid="CR53">53</xref>]. Little is known about a possible relationship between COVID-19 and cardiovascular disease. An early report on 99 patients hospitalised from 1st to 20th January 2020 at Jinyntan Hospital, Wuhan, China, for SARS-CoV-2-related pneumonia, shows that pre-existing cardiovascular disease was present in 40% of them [<xref ref-type="bibr" rid="CR7">7</xref>]. A second report from the same period of time on 138 patients hospitalised at Zhongnan Hospital of Wuhan University shows that 26% of the patients required cardiologic intensive care. Among these patients, 16.7% developed arrhythmias and 7.2% experienced an acute coronary syndrome in addition to other complications [<xref ref-type="bibr" rid="CR51">51</xref>]. Furthermore, patients diagnosed with pneumonia due to SARS-CoV-2 infection showed an increase in high-sensitivity cardiac troponin I levels, suggesting myocardial injury [<xref ref-type="bibr" rid="CR23">23</xref>]. Other published and anecdotal reports indicate the presence of myocarditis, cardiac arrest, and acute heart failure in SARS-CoV-2- infected patients. It is not clear whether these cardiac conditions are provoked by SARS-CoV-2 or are complications typical of any other pathology with higher cardio-metabolic demand, and thus unrelated to the viral infection. Epidemiological studies conducted during the flu epidemic in USA in 1990 show that influenza and its related complications, such as secondary pneumonia, may cause myocardial infarction due to inflammation-induced destabilisation of coronary artery plaques [<xref ref-type="bibr" rid="CR10">10</xref>]. This results from multiple mechanisms, such as tachycardia, hypoxia, increased wall stress, and thrombophilia or release of inflammatory cytokines [<xref ref-type="bibr" rid="CR11">11</xref>]. So, a possible causal link cannot be excluded.</p><p id="Par3">A similar link with myocardial infarction and acute heart failure was shown for the recent epidemics of SARS-CoV and MERS-nCoV [<xref ref-type="bibr" rid="CR53">53</xref>]. In the absence of a specific treatment or a vaccine, which, according to experts, will not be ready before a year from now, there are only three possible remedies: (1) attempts to contain the spread of the infection with drastic and likely unpopular measures, such as quarantine or restriction of free movement in a specific area with the aim of getting the epidemic exhaust itself “naturally”. This, hopefully, should be facilitated by the coming of the summer in the Northern hemisphere; (2) supportive treatment of respiratory and cardiologic complications of the infection, including admission to intensive care units (ICUS) and use of mechanical ventilation or extracorporeal membrane oxygenation (ECMO); (3) proposal of novel approaches, based on evidence from a variety of fields of expertise, which could help in finding a possible therapy. With our short report, we would like to contribute with our experience on Notch signalling to the third option.</p></sec><sec id="Sec3"><title>Cardiovascular drugs in the context of COVID-19</title><p id="Par4">CoVs are enveloped single-stranded positive-sense RNA viruses with genomes ranging between 26.2 and 31.7 kb RNA. The genome encodes four major structural proteins: the spike (S) protein, nucleocapsid (N) protein, membrane (M) protein, and the envelope (E) protein, all required to produce the viral particle [<xref ref-type="bibr" rid="CR46">46</xref>]. Sequencing analyses on RNA of SARS-CoV-2 variants isolated from COVID-19 patients show 96% homology with a bat virus [<xref ref-type="bibr" rid="CR54">54</xref>] suggesting that, as for the other coronaviruses, SARS-CoV-2 jumped from bats to humans, probably through an intermediate host, not yet identified, after the occurrence of a mutation that allowed the infection of human cells [<xref ref-type="bibr" rid="CR3">3</xref>]. The S (spike) glycoprotein mediates the SARS-CoV-2 entry into cells following the binding to the angiotensin converting enzyme 2 (ACE2) [<xref ref-type="bibr" rid="CR22">22</xref>]. ACE2 is highly expressed on cell surface of many tissues and organs including the lungs and the myocardium [<xref ref-type="bibr" rid="CR53">53</xref>]. Of relevance, ACE2 is mainly located in the inner track of the respiratory system, thus explaining why SARS-CoV-2, differently from the flu virus which binds to the upper airways track, might cause serious respiratory insufficiency. This also explains why COVID-19 is not just a common influenza, like somebody believed [<xref ref-type="bibr" rid="CR33">33</xref>]. Differently from ACE1, which catalyses the formation of Angiotensin (Ang) II, the active component of renin–angiotensin system involved in blood pressure regulation and cardiorenal function, ACE2 cleaves Ang II in Ang (1–7). Thus, ACE2 antagonises ACE1 activity. Ang II receptor blockers (ARBs), which are widely used to treat hypertension and heart failure, increase the levels of Ang II [<xref ref-type="bibr" rid="CR44">44</xref>] and, indirectly, could activate ACE2 [<xref ref-type="bibr" rid="CR1">1</xref>]. It has been proposed that patients receiving ARBs have higher susceptibility to COVID-19 [<xref ref-type="bibr" rid="CR15">15</xref>] and, as a consequence, hypertensive or patients with heart failure should switch from ARBs to other drugs. This way of thinking, however, is not supported by any evidence [<xref ref-type="bibr" rid="CR16">16</xref>]. Actually, there are caveats here: (1) ACE2 expression is reduced in hypertension models; (2) there is no evidence of increased ACE2 expression with ARBs in the lung; (3) hypertension and its treatment with ARBs did not affect previous coronavirus infections [<xref ref-type="bibr" rid="CR16">16</xref>].</p><p id="Par5">Based on the evidence discussed above, ACE2 could be targeted to prevent SARS-CoV-2 from entering the cells. To this aim, Lei et al. generated a recombinant protein by connecting the extracellular domain of human ACE2 to the Fc region of the human immunoglobulin IgG1 which neutralised SARS-CoV and SARS-CoV-2 in vitro [<xref ref-type="bibr" rid="CR27">27</xref>]. Another approach to prevent viral infection could be the downregulation of ACE2 on cell membrane. Of relevance, ADAM17 (A Disintegrin And Metalloproteases 17), a metalloprotease significantly expressed also in the lungs and heart, is involved in the shedding of surface proteins, including ACE2 [<xref ref-type="bibr" rid="CR26">26</xref>]. Ablation of ADAM17 expression reduces ACE2 shedding, whereas overexpression of ADAM17 significantly increases its shedding [<xref ref-type="bibr" rid="CR26">26</xref>]. Furthermore, membrane translocation of ADAM17 leads to a reduction in myocardial ACE2 protein levels and activity which is associated with an increase in plasma ACE2 activity [<xref ref-type="bibr" rid="CR32">32</xref>]. Based on these data, it is tempting to speculate that increasing ADAM17 levels and/or activity to enhance shedding and increase soluble/plasma ACE2 levels could represent a way of blocking SARS-CoV-2 entry into cells (Fig. <xref rid="Fig1" ref-type="fig">1</xref>a). Of relevance, treatment with the chemotherapeutic agent 5-fluorouracil strongly activates ADAM17 in an animal model of colorectal cancer [<xref ref-type="bibr" rid="CR25">25</xref>]. Furthermore, in non-small cell lung cancer cell lines, estradiol increases the expression levels and activity of ADAM17 [<xref ref-type="bibr" rid="CR41">41</xref>]. This last finding would suggest higher shedding of ACE2 in women and could, at least partially, explain the reduced incidence of COVID-19 in women compared to men [<xref ref-type="bibr" rid="CR19">19</xref>].<fig id="Fig1"><label>Fig. 1</label><caption><p><bold> a</bold> Severe acute respiratory syndrome- coronavirus-2 (SARS-CoV-2) entry into the cells is mediated by the binding of the viral spike (S) glycoprotein to the angiotensin converting enzyme 2 (ACE2) on the cells, followed by the proteolytic cut at the S<sub>1</sub>/S<sub>2</sub> site of the S glycoprotein by the host protease furin. ACE2 levels on the plasma membrane are regulated by ADAM17, which promotes the shedding of the protein. The Notch signalling is a positive regulator of furin and a negative regulator of ADAM17 (through the transcription of miRNA-145), and thus γ-secretase inhibitor (GSI), which prevents Notch activation, may represent a strategy to interfere with the virus entry into the cells by reducing furin and increase ADAM17 shedding. An antagomir to miRNA-145 could represent an alternative approach for upregulation of ADAM17. <bold>b</bold> Notch precursor is cleaved by furin in the Golgi apparatus leading to a heterodimer on the plasma membrane consisting of Notch extracellular domain (NECD) and Notch transmembrane (TM), which contains the Notch intracellular domain (NICD). After the binding with the ligand, Notch is cleaved by ADAM (A Disintegrin And Metalloprotease) 10 or 17, and, after, by the γ-secretase complex. The resultant NICD translocates into the nucleus, where it interacts with the transcription factor CSL (CBF-1/RBP-Jk/Suppressor of hairless/Lag-1) and the transcriptional co-activator MAML (mastermind-like) to regulate the transcription of Notch target genes, such as HEY1 and 2, HES1, FURIN, and miRNA-145</p></caption><graphic xlink:href="395_2020_791_Fig1_HTML" id="MO1"></graphic></fig></p><p id="Par6">Other than ACE2, the protease furin is also required to promote entrance of the virus into the cell [<xref ref-type="bibr" rid="CR50">50</xref>]. Furin, a member of the subtilisin-like proprotein convertase family that processes protein of the secretory pathway, is a type 1 membrane-bound protease that is expressed in multiple organs, including the lungs. SARS-CoV-2, differently from SARS-CoV, presents a furin cleavage site between the S1/S2 subunits of the S glycoprotein. Following the binding of the S glycoprotein to ACE2, furin-mediated proteolytic cut of the S protein is necessary for viral entry into the cell [<xref ref-type="bibr" rid="CR50">50</xref>]. Inhibiting the expression of furin could then be a possible approach to prevent SARS-CoV-2 infection (Fig. <xref rid="Fig1" ref-type="fig">1</xref>a, b). Of relevance in this context, nanomolar concentrations of a peptide designed from the furin cleavage sequence of the avian influenza A H5N1 virus provide protection against infection by several furin-dependent pathogens [<xref ref-type="bibr" rid="CR47">47</xref>].</p><p id="Par7">Furin and ADAM17 are both intertwined with Notch, an evolutionarily conserved system of communication between adjacent cells, and thus targeting Notch could represent an alternative approach to inhibit furin and upregulate ADAM17 (Fig. <xref rid="Fig1" ref-type="fig">1</xref>b). Of interest, a recent study has investigated the physical association between SARS-CoV-2 and human proteins, identifying 66 potential cellular proteins that could be targeted to prevent viral infection [<xref ref-type="bibr" rid="CR13">13</xref>]. With this approach, it is impossible to identify host proteins crucial for viral infection, which do not interact directly with viral proteins, as is the case for furin and ADAM17. Thus, hypothesis-driven studies based on the knowledge of the molecular details of virus–cell interaction are still crucial for the identification of therapeutic targets to treat COVID-19.</p></sec><sec id="Sec4"><title>Targeting Notch to prevent SARS-CoV-2 infection</title><p id="Par8">The Notch signalling pathway plays a major role in controlling cell fate during the development and in postnatal life [<xref ref-type="bibr" rid="CR2">2</xref>]. Growing evidence shows that the Notch signalling is involved in maintaining the homeostasis of the cardiovascular system and could represent a novel target to reduce atherosclerosis progression [<xref ref-type="bibr" rid="CR18">18</xref>, <xref ref-type="bibr" rid="CR42">42</xref>] and remodelling following a myocardial infarction [<xref ref-type="bibr" rid="CR17">17</xref>, <xref ref-type="bibr" rid="CR20">20</xref>, <xref ref-type="bibr" rid="CR34">34</xref>]. In humans, there are four receptors (Notch1–4) activated by binding with ligands (Jagged1,2 and Delta-like ligands (Dll)1,3,4) on the surface of adjacent cells [<xref ref-type="bibr" rid="CR2">2</xref>]. Notch precursor is first cleaved by furin in the Golgi apparatus and then is found as a heterodimer on the cell membrane. Following ligand binding, Notch is first cleaved at the cell membrane by ADAM10 or ADAM17 thus enabling the final cleavage by the γ-secretase releasing the active Notch intracellular domain which migrates to the nucleus and regulates the transcription of target genes (Fig. <xref rid="Fig1" ref-type="fig">1</xref>b).</p><p id="Par9">Furin is transcriptionally induced by Notch1 [<xref ref-type="bibr" rid="CR38">38</xref>]. Inhibition of Notch signalling could, then, be useful to reduce furin levels and interfere with viral entry into the cell. Since Notch dysregulation is a feature of the majority of cancers, Notch inhibitors that target the γ-secretase are available and are being tested, with manageable gastrointestinal toxicity, in several clinical trials in cancer patients. Favorable response has been so far obtained in a limited number of patients indicating that it will be crucial to develop new strategies to identify “responders” to Notch inhibition-based cancer therapies [<xref ref-type="bibr" rid="CR2">2</xref>].</p><p id="Par10">Notch1-dependent enhancement of furin activity activates ADAM10 but not ADAM17 [<xref ref-type="bibr" rid="CR38">38</xref>], suggesting that Notch1 does not control ADAM17. Nevertheless, a study on abdominal aorta showed that ADAM17 expression is downregulated by the γ-secretase inhibitor (GSI) DAPT [<italic>N</italic>‐(<italic>N</italic>‐[3,5‐difluorophenacetyl]‐<sc>l</sc>‐alanyl)‐<italic>S</italic>‐phenylglycine <italic>t</italic>‐butyl ester]) [<xref ref-type="bibr" rid="CR8">8</xref>]. Since GSIs with different specificities toward each isoform of Notch exist [<xref ref-type="bibr" rid="CR2">2</xref>], more of these compounds could be tested to investigate their effects on ADAM17 and, possibly, on ACE2 shedding. Of interest, miRNA-145, which downregulates ADAM17 [<xref ref-type="bibr" rid="CR14">14</xref>], is a target of Jagged1/Notch1 signalling in vascular smooth muscle cells [<xref ref-type="bibr" rid="CR4">4</xref>]. It would be of interest to investigate whether antagomir to miRNA-145 would increase ADAM17 activity (Fig. <xref rid="Fig1" ref-type="fig">1</xref>a).</p></sec><sec id="Sec5"><title>Notch and the “cytokine storm”</title><p id="Par11">Among the proposed mechanisms of myocardial and lung injury caused by SARS-CoV-2, there is a “cytokine storm” triggered by an imbalanced response by type 1 and type 2 T helper (Th) cells [<xref ref-type="bibr" rid="CR53">53</xref>]. The Notch pathway plays a major role during the differentiation and the activity of innate and adaptive immune cells [<xref ref-type="bibr" rid="CR30">30</xref>, <xref ref-type="bibr" rid="CR49">49</xref>]. Dll4/Notch signalling is an important inducer of M1 macrophage polarisation and experiments in vitro and in vivo have shown that inhibition of the Notch by GSI or by anti-Dll4 antibodies leads to a dampening of the inflammation [<xref ref-type="bibr" rid="CR49">49</xref>]. In macrophages, Notch1 directly binds to interleukin (IL)-6 promoter in response to interferon (IFN)-γ and positively regulates IL-6 production [<xref ref-type="bibr" rid="CR52">52</xref>]. It is important to underline that IL-6, in turn, increases the expression of the Notch ligand Dll1, thus amplifying the Notch signalling and establishing a positive feedback loop that promotes the further production of IL-6 [<xref ref-type="bibr" rid="CR21">21</xref>]. In Th cells, Notch signalling triggered by Dll1,4 ligands promotes the production of inflammatory Th1/Th17 cytokines, whereas Jagged1 suppresses IL-6-induced Th17 activation [<xref ref-type="bibr" rid="CR49">49</xref>] (Fig. <xref rid="Fig2" ref-type="fig">2</xref>). A multicentre randomised controlled trial to test a monoclonal antibody against the IL-6 receptor (tocilizumab, Roche) in patients with COVID-19 pneumonia and elevated IL-6 has been conducted in China with promising results (ChiCTR2000029765). Based on these results, a phase II clinical trial to test the efficacy of tocilizumab in 330 Italian patients with COVID-19 pneumonia has been approved by the Italian Medicines Agency (<ext-link ext-link-type="uri" xlink:href="https://www.agenziafarmaco.gov.it/en">https://www.agenziafarmaco.gov.it/en</ext-link>) and a phase III clinical trial enrolling 330 patients globally has been announced in the US (<ext-link ext-link-type="uri" xlink:href="https://www.roche.com/media/releases/med-cor-2020-03-19.htm">https://www.roche.com/media/releases/med-cor-2020-03-19.htm</ext-link>). In addition, other strategies have been attempted to reduce the cytokine storm. CytoSorb is an extracorporeal cytokine adsorber and, according to the manufacturers, over 65 patients with severe COVID-19 have been treated with CytoSorb in China, Italy and Germany (<ext-link ext-link-type="uri" xlink:href="https://cytosorb-therapy.com/en/covid-19">https://cytosorb-therapy.com/en/covid-19</ext-link>). However, data on the effectiveness of this approach are not yet available.<fig id="Fig2"><label>Fig. 2</label><caption><p>Notch and IL-6 cooperate to activate the immune system and perpetuate the cytokine storm. In macrophages, Dll4/Notch signalling promotes the production of inflammatory cytokines, IL-6 among those. IL-6, in turn, increases the expression of the Notch ligands (Dll1,4), thus amplifying the Notch signalling and establishing a feedback loop that promotes the further production of IL-6. In T cells, Notch signalling triggered by Dll1/Dll4 ligands promote inflammatory Th1/Th17 cytokines; on the contrary, Jagged1 ligands dampen IL-6-induced Th17 activation. Tocilizumab is expected to block cytokine storm and prevent tissue damage. Notch inhibition by blocking Dll1,4 ligands may help to interrupt the positive feedback loop that fuels the cytokine storm. <italic>M</italic> Macrophages, <italic>T</italic> T cells</p></caption><graphic xlink:href="395_2020_791_Fig2_HTML" id="MO2"></graphic></fig></p><p id="Par12">IL-6 is a predictor of mortality in COVID-19 patients [<xref ref-type="bibr" rid="CR43">43</xref>]. However, in severely affected patients, IL-6 is moderately increased (25.2 pg/mL) [<xref ref-type="bibr" rid="CR36">36</xref>] compared to typical levels in cytokine release syndromes (more than 1600 pg/mL in sepsis) [<xref ref-type="bibr" rid="CR29">29</xref>]. This may explain why no serious vasoplegic shocks were observed. Nevertheless, the cytokine storm in COVID19 patients is characterised not only by hyperinnate immune response but also by activation of Th cell-mediated immunity. In this scenario, the idea of combining Notch inhibitors with anti-IL-6 to dampen the cytokine storm is captivating (Fig. <xref rid="Fig2" ref-type="fig">2</xref>).</p><p id="Par13">However, it must be also considered that Notch inhibition could interfere with the immune response during viral infection. Ito et al. [<xref ref-type="bibr" rid="CR24">24</xref>] found that in mice infected with influenza A virus (H1N1), macrophages increase Notch ligand Dll1 expression. In these mice, inhibition of the Notch pathway using an anti-Dll1 antibody, or GSI by intranasal administration, resulted in increased mortality, defective viral clearance, and decreased IFN-γ production in lungs [<xref ref-type="bibr" rid="CR24">24</xref>]. Notch signalling also modulates the immune response following respiratory syncytial virus (RSV) infection [<xref ref-type="bibr" rid="CR28">28</xref>]. Of note, it has been reported that RSV infection causes an increase of Jagged1 in bronchial epithelial cells and, when co-cultured with CD4 + T cells, promotes Th2 differentiation. Conversely, the reduction of Jagged1 expression with siRNA abrogates this effect and promotes an increase in Th1 differentiation. On this basis, it has been suggested that Jagged1-mediated Th2 differentiation may cause RSV-induced airway hyper-responsiveness [<xref ref-type="bibr" rid="CR37">37</xref>]. On the basis of these studies, it could be hypothesised that it may be preferable targeting specific components of the Notch signalling, such as Dll4 or Jagged1, rather than inhibiting Notch with a GSI. Of relevance, soluble Jagged1 has been shown to efficiently inhibit neointima formation after balloon injury by decreasing smooth muscle cell proliferation and migration through inhibition of Notch signalling [<xref ref-type="bibr" rid="CR5">5</xref>].</p><p id="Par14">Preclinical studies have shown that Notch inhibition can be useful not only for treatment of atherosclerosis but also for other inflammation-based conditions such as graft-versus-host disease [<xref ref-type="bibr" rid="CR39">39</xref>], chronic obstructive pulmonary disease (COPD) [<xref ref-type="bibr" rid="CR12">12</xref>] and arthritis [<xref ref-type="bibr" rid="CR31">31</xref>]. It is important to point out that before Notch inhibition becomes a reality in the clinical managements of these patients, we should address issues that could arise upon chronic exposure to Notch inhibitors, likely required for many of these pathologies, such as (1) toxicity related to the multiple cellular targets of GSIs, due to the promiscuous activity of the γ-secretase, (2) alteration of the immune system activities and of the stem cell compartment, in which Notch plays a pivotal role, and (3) the potential oncogenicity of the treatment, given the tumour suppressor role of Notch in tissues like the skin, as observed in Alzheimer’s patient treated with GSIs to inhibit the formation of amyloid A4 peptide [<xref ref-type="bibr" rid="CR2">2</xref>, <xref ref-type="bibr" rid="CR35">35</xref>]. A possible approach to avoid systemic toxicity could be delivery of GSIs and Jagged1/Dll4 inhibitors directly to the lungs by the use of nanoparticles [<xref ref-type="bibr" rid="CR45">45</xref>].</p><p id="Par15">Based on these data, we should conclude that, even if it holds great promise, Notch inhibition to block the cytokine storm in COVID-19 patients is still not feasible and targeting the IL-6 receptor or depleting the cytokines by other means represent the only approaches available at this time.</p></sec><sec id="Sec6"><title>Conclusions</title><p id="Par16">The relationship between Notch and viruses is well documented. To replicate, some viruses, such as Human Papilloma Virus and Simian Virus 40, highjack the cell machinery, including the Notch signalling, and by doing so they can cause cancer [<xref ref-type="bibr" rid="CR9">9</xref>]. Therefore, it has been proposed that the dysregulation of Notch signalling could provide diagnostic and therapeutic tools for virus-associated cancers [<xref ref-type="bibr" rid="CR9">9</xref>]. By uncovering new aspects of this relationship, we might be able to target Notch also to fight heart and lung disease caused directly by SARS-CoV-2 infection and by the cytokine storm in response to the virus.</p></sec></body><back><notes notes-type="ethics"><title>Compliance with ethical standards</title><notes notes-type="COI-statement"><title>Conflict of interest</title><p id="Par17">The authors declare that they have no conflict of interest.</p></notes></notes><ref-list id="Bib1"><title>References</title><ref id="CR1"><label>1.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Agata</surname><given-names>J</given-names></name><name><surname>Ura</surname><given-names>N</given-names></name><name><surname>Yoshida</surname><given-names>H</given-names></name><name><surname>Shinshi</surname><given-names>Y</given-names></name><name><surname>Sasaki</surname><given-names>H</given-names></name><name><surname>Hyakkoku</surname><given-names>M</given-names></name><name><surname>Taniguchi</surname><given-names>S</given-names></name><name><surname>Shimamoto</surname><given-names>K</given-names></name></person-group><article-title>Olmesartan is an angiotensin II receptor blocker with an inhibitory effect on angiotensin-converting enzyme</article-title><source>Hypertens Res</source><year>2006</year><volume>29</volume><fpage>865</fpage><lpage>874</lpage><pub-id pub-id-type="doi">10.1291/hypres.29.865</pub-id><pub-id pub-id-type="pmid">17345786</pub-id></element-citation></ref><ref id="CR2"><label>2.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Aquila</surname><given-names>G</given-names></name><name><surname>Kostina</surname><given-names>A</given-names></name><name><surname>Vieceli Dalla Sega</surname><given-names>F</given-names></name><name><surname>Shlyakhto</surname><given-names>E</given-names></name><name><surname>Kostareva</surname><given-names>A</given-names></name><name><surname>Marracino</surname><given-names>L</given-names></name><name><surname>Ferrari</surname><given-names>R</given-names></name><name><surname>Rizzo</surname><given-names>P</given-names></name><name><surname>Malaschicheva</surname><given-names>A</given-names></name></person-group><article-title>The Notch pathway: a novel therapeutic target for cardiovascular diseases?</article-title><source>Expert Opin Ther Targets</source><year>2019</year><volume>23</volume><fpage>695</fpage><lpage>710</lpage><pub-id pub-id-type="doi">10.1080/14728222.2019.1641198</pub-id><pub-id pub-id-type="pmid">31304807</pub-id></element-citation></ref><ref id="CR3"><label>3.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Benvenuto</surname><given-names>D</given-names></name><name><surname>Giovanetti</surname><given-names>M</given-names></name><name><surname>Ciccozzi</surname><given-names>A</given-names></name><name><surname>Spoto</surname><given-names>S</given-names></name><name><surname>Angeletti</surname><given-names>S</given-names></name><name><surname>Ciccozzi</surname><given-names>M</given-names></name></person-group><article-title>The 2019-new coronavirus epidemic: evidence for virus evolution</article-title><source>J Med Virol</source><year>2020</year><volume>92</volume><fpage>455</fpage><lpage>459</lpage><pub-id pub-id-type="doi">10.1002/jmv.25688</pub-id><pub-id pub-id-type="pmid">31994738</pub-id></element-citation></ref><ref id="CR4"><label>4.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Boucher</surname><given-names>JM</given-names></name><name><surname>Peterson</surname><given-names>SM</given-names></name><name><surname>Urs</surname><given-names>S</given-names></name><name><surname>Zhang</surname><given-names>C</given-names></name><name><surname>Liaw</surname><given-names>L</given-names></name></person-group><article-title>The miR-143/145 cluster is a novel transcriptional target of Jagged-1/Notch signaling in vascular smooth muscle cells</article-title><source>J Biol Chem</source><year>2011</year><volume>286</volume><fpage>28312</fpage><lpage>28321</lpage><pub-id pub-id-type="doi">10.1074/jbc.M111.221945</pub-id><pub-id pub-id-type="pmid">21685392</pub-id></element-citation></ref><ref id="CR5"><label>5.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Caolo</surname><given-names>V</given-names></name><name><surname>Schulten</surname><given-names>HM</given-names></name><name><surname>Zhuang</surname><given-names>ZW</given-names></name><name><surname>Murakami</surname><given-names>M</given-names></name><name><surname>Wagenaar</surname><given-names>A</given-names></name><name><surname>Verbruggen</surname><given-names>S</given-names></name><name><surname>Molin</surname><given-names>DG</given-names></name><name><surname>Post</surname><given-names>MJ</given-names></name></person-group><article-title>Soluble Jagged-1 inhibits neointima formation by attenuating Notch-Herp2 signaling</article-title><source>Arterioscler Thromb Vasc Biol</source><year>2011</year><volume>31</volume><fpage>1059</fpage><lpage>1065</lpage><pub-id pub-id-type="doi">10.1161/ATVBAHA.110.217935</pub-id><pub-id pub-id-type="pmid">21330605</pub-id></element-citation></ref><ref id="CR6"><label>6.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Carbone</surname><given-names>M</given-names></name><name><surname>Green</surname><given-names>JB</given-names></name><name><surname>Bucci</surname><given-names>EM</given-names></name><name><surname>Lednicky</surname><given-names>JJ</given-names></name></person-group><article-title>Editorial: Coronaviruses: Facts, Myths and Hypotheses</article-title><source>J Thorac Oncol</source><year>2020</year><pub-id pub-id-type="doi">10.1016/j.jtho.2020.02.024</pub-id><pub-id pub-id-type="pmid">32151778</pub-id></element-citation></ref><ref id="CR7"><label>7.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Chen</surname><given-names>N</given-names></name><name><surname>Zhou</surname><given-names>M</given-names></name><name><surname>Dong</surname><given-names>X</given-names></name><name><surname>Qu</surname><given-names>J</given-names></name><name><surname>Gong</surname><given-names>F</given-names></name><name><surname>Han</surname><given-names>Y</given-names></name><name><surname>Qiu</surname><given-names>Y</given-names></name><name><surname>Wang</surname><given-names>J</given-names></name><name><surname>Liu</surname><given-names>Y</given-names></name><name><surname>Wei</surname><given-names>Y</given-names></name><name><surname>Xia</surname><given-names>J</given-names></name><name><surname>Yu</surname><given-names>T</given-names></name><name><surname>Zhang</surname><given-names>X</given-names></name><name><surname>Zhang</surname><given-names>L</given-names></name></person-group><article-title>Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study</article-title><source>Lancet</source><year>2020</year><volume>395</volume><fpage>507</fpage><lpage>513</lpage><pub-id pub-id-type="doi">10.1016/S0140-6736(20)30211-7</pub-id><pub-id pub-id-type="pmid">32007143</pub-id></element-citation></ref><ref id="CR8"><label>8.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Cheng</surname><given-names>J</given-names></name><name><surname>Koenig</surname><given-names>SN</given-names></name><name><surname>Kuivaniemi</surname><given-names>HS</given-names></name><name><surname>Garg</surname><given-names>V</given-names></name><name><surname>Hans</surname><given-names>CP</given-names></name></person-group><article-title>Pharmacological inhibitor of notch signaling stabilizes the progression of small abdominal aortic aneurysm in a mouse model</article-title><source>J Am Heart Assoc</source><year>2014</year><volume>3</volume><fpage>e001064</fpage><pub-id pub-id-type="doi">10.1161/JAHA.114.001064</pub-id><pub-id pub-id-type="pmid">25349182</pub-id></element-citation></ref><ref id="CR9"><label>9.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>AaRPaMFaTM</surname><given-names>C</given-names></name></person-group><article-title>Roles of dysregulated Notch pathway and small DNA tumor viruses in cancer initiation and progression</article-title><source>J Cancer Metastasis Treat</source><year>2015</year><pub-id pub-id-type="doi">10.4103/2394-4722.171982</pub-id></element-citation></ref><ref id="CR10"><label>10.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Collins</surname><given-names>SD</given-names></name></person-group><article-title>Excess mortality from causes other than influenza and pneumonia during influenza epidemics</article-title><source>Public Health Rep</source><year>1932</year><volume>47</volume><fpage>2159</fpage><lpage>2179</lpage><pub-id pub-id-type="doi">10.2307/4580606</pub-id><pub-id pub-id-type="pmid">19315373</pub-id></element-citation></ref><ref id="CR11"><label>11.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Corrales-Medina</surname><given-names>VF</given-names></name><name><surname>Madjid</surname><given-names>M</given-names></name><name><surname>Musher</surname><given-names>DM</given-names></name></person-group><article-title>Role of acute infection in triggering acute coronary syndromes</article-title><source>Lancet Infect Dis</source><year>2010</year><volume>10</volume><fpage>83</fpage><lpage>92</lpage><pub-id pub-id-type="doi">10.1016/S1473-3099(09)70331-7</pub-id><pub-id pub-id-type="pmid">20113977</pub-id></element-citation></ref><ref id="CR12"><label>12.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Danahay</surname><given-names>H</given-names></name><name><surname>Pessotti</surname><given-names>AD</given-names></name><name><surname>Coote</surname><given-names>J</given-names></name><name><surname>Montgomery</surname><given-names>BE</given-names></name><name><surname>Xia</surname><given-names>D</given-names></name><name><surname>Wilson</surname><given-names>A</given-names></name><name><surname>Yang</surname><given-names>H</given-names></name><name><surname>Wang</surname><given-names>Z</given-names></name><name><surname>Bevan</surname><given-names>L</given-names></name><name><surname>Thomas</surname><given-names>C</given-names></name><name><surname>Petit</surname><given-names>S</given-names></name><name><surname>London</surname><given-names>A</given-names></name><name><surname>LeMotte</surname><given-names>P</given-names></name><name><surname>Doelemeyer</surname><given-names>A</given-names></name><name><surname>Vélez-Reyes</surname><given-names>GL</given-names></name><name><surname>Bernasconi</surname><given-names>P</given-names></name><name><surname>Fryer</surname><given-names>CJ</given-names></name><name><surname>Edwards</surname><given-names>M</given-names></name><name><surname>Capodieci</surname><given-names>P</given-names></name><name><surname>Chen</surname><given-names>A</given-names></name><name><surname>Hild</surname><given-names>M</given-names></name><name><surname>Jaffe</surname><given-names>AB</given-names></name></person-group><article-title>Notch2 is required for inflammatory cytokine-driven goblet cell metaplasia in the lung</article-title><source>Cell Rep</source><year>2015</year><volume>10</volume><fpage>239</fpage><lpage>252</lpage><pub-id pub-id-type="doi">10.1016/j.celrep.2014.12.017</pub-id><pub-id pub-id-type="pmid">25558064</pub-id></element-citation></ref><ref id="CR13"><label>13.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>David</surname><given-names>EG</given-names></name><name><surname>Gwendolyn</surname><given-names>MJ</given-names></name><name><surname>Mehdi</surname><given-names>B</given-names></name><name><surname>Jiewei</surname><given-names>X</given-names></name><name><surname>Kirsten</surname><given-names>O</given-names></name><etal></etal></person-group><article-title>A SARS-CoV-2-human protein-protein interaction map reveals drug targets and potential drug-repurposing</article-title><source>BioRxiv</source><year>2020</year><pub-id pub-id-type="doi">10.1101/2020.03.22.002386</pub-id></element-citation></ref><ref id="CR14"><label>14.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Doberstein</surname><given-names>K</given-names></name><name><surname>Steinmeyer</surname><given-names>N</given-names></name><name><surname>Hartmetz</surname><given-names>AK</given-names></name><name><surname>Eberhardt</surname><given-names>W</given-names></name><name><surname>Mittelbronn</surname><given-names>M</given-names></name><name><surname>Harter</surname><given-names>PN</given-names></name><name><surname>Juengel</surname><given-names>E</given-names></name><name><surname>Blaheta</surname><given-names>R</given-names></name><name><surname>Pfeilschifter</surname><given-names>J</given-names></name><name><surname>Gutwein</surname><given-names>P</given-names></name></person-group><article-title>MicroRNA-145 targets the metalloprotease ADAM17 and is suppressed in renal cell carcinoma patients</article-title><source>Neoplasia</source><year>2013</year><volume>15</volume><fpage>218</fpage><lpage>230</lpage><pub-id pub-id-type="doi">10.1593/neo.121222</pub-id><pub-id pub-id-type="pmid">23441135</pub-id></element-citation></ref><ref id="CR15"><label>15.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fang</surname><given-names>L</given-names></name><name><surname>Karakiulakis</surname><given-names>G</given-names></name><name><surname>Roth</surname><given-names>M</given-names></name></person-group><article-title>Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?</article-title><source>Lancet Respir Med</source><year>2020</year><pub-id pub-id-type="doi">10.1016/S2213-2600(20)30116-8</pub-id><pub-id pub-id-type="pmid">32222169</pub-id></element-citation></ref><ref id="CR16"><label>16.</label><mixed-citation publication-type="other">Ferrari R, Di Pasquale G, Rapezzi C (2020) 2019 CORONAVIRUS: which implications for cardiology? Eur J Prev Cardiol. 10.1177/2047487320918102</mixed-citation></ref><ref id="CR17"><label>17.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ferrari</surname><given-names>R</given-names></name><name><surname>Rizzo</surname><given-names>P</given-names></name></person-group><article-title>The Notch pathway: a novel target for myocardial remodelling therapy?</article-title><source>Eur Heart J</source><year>2014</year><volume>35</volume><fpage>2140</fpage><lpage>2145</lpage><pub-id pub-id-type="doi">10.1093/eurheartj/ehu244</pub-id><pub-id pub-id-type="pmid">24970336</pub-id></element-citation></ref><ref id="CR18"><label>18.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Fortini</surname><given-names>F</given-names></name><name><surname>Vieceli Dalla Sega</surname><given-names>F</given-names></name><name><surname>Caliceti</surname><given-names>C</given-names></name><name><surname>Lambertini</surname><given-names>E</given-names></name><name><surname>Pannuti</surname><given-names>A</given-names></name><name><surname>Peiffer</surname><given-names>DS</given-names></name><name><surname>Balla</surname><given-names>C</given-names></name><name><surname>Rizzo</surname><given-names>P</given-names></name></person-group><article-title>Estrogen-mediated protection against coronary heart disease: the role of the Notch pathway</article-title><source>J Steroid Biochem Mol Biol</source><year>2019</year><volume>189</volume><fpage>87</fpage><lpage>100</lpage><pub-id pub-id-type="doi">10.1016/j.jsbmb.2019.02.008</pub-id><pub-id pub-id-type="pmid">30817989</pub-id></element-citation></ref><ref id="CR19"><label>19.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Guan</surname><given-names>WJ</given-names></name><name><surname>Ni</surname><given-names>ZY</given-names></name><name><surname>Hu</surname><given-names>Y</given-names></name><name><surname>Liang</surname><given-names>WH</given-names></name><name><surname>Ou</surname><given-names>CQ</given-names></name><name><surname>He</surname><given-names>JX</given-names></name><name><surname>Liu</surname><given-names>L</given-names></name><name><surname>Shan</surname><given-names>H</given-names></name><name><surname>Lei</surname><given-names>CL</given-names></name><name><surname>Hui</surname><given-names>DSC</given-names></name><name><surname>Du</surname><given-names>B</given-names></name><name><surname>Li</surname><given-names>LJ</given-names></name><name><surname>Zeng</surname><given-names>G</given-names></name><name><surname>Yuen</surname><given-names>KY</given-names></name><name><surname>Chen</surname><given-names>RC</given-names></name><name><surname>Tang</surname><given-names>CL</given-names></name><name><surname>Wang</surname><given-names>T</given-names></name><name><surname>Chen</surname><given-names>PY</given-names></name><name><surname>Xiang</surname><given-names>J</given-names></name><name><surname>Li</surname><given-names>SY</given-names></name><name><surname>Wang</surname><given-names>JL</given-names></name><name><surname>Liang</surname><given-names>ZJ</given-names></name><name><surname>Peng</surname><given-names>YX</given-names></name><name><surname>Wei</surname><given-names>L</given-names></name><name><surname>Liu</surname><given-names>Y</given-names></name><name><surname>Hu</surname><given-names>YH</given-names></name><name><surname>Peng</surname><given-names>P</given-names></name><name><surname>Wang</surname><given-names>JM</given-names></name><name><surname>Liu</surname><given-names>JY</given-names></name><name><surname>Chen</surname><given-names>Z</given-names></name><name><surname>Li</surname><given-names>G</given-names></name><name><surname>Zheng</surname><given-names>ZJ</given-names></name><name><surname>Qiu</surname><given-names>SQ</given-names></name><name><surname>Luo</surname><given-names>J</given-names></name><name><surname>Ye</surname><given-names>CJ</given-names></name><name><surname>Zhu</surname><given-names>SY</given-names></name><name><surname>Zhong</surname><given-names>NS</given-names></name><collab>Covid-19 CMTEGf</collab></person-group><article-title>Clinical Characteristics of Coronavirus Disease 2019 in China</article-title><source>N Engl J Med</source><year>2020</year><pub-id pub-id-type="doi">10.1056/NEJMoa2002032</pub-id><pub-id pub-id-type="pmid">32220206</pub-id></element-citation></ref><ref id="CR20"><label>20.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Gude</surname><given-names>N</given-names></name><name><surname>Joyo</surname><given-names>E</given-names></name><name><surname>Toko</surname><given-names>H</given-names></name><name><surname>Quijada</surname><given-names>P</given-names></name><name><surname>Villanueva</surname><given-names>M</given-names></name><name><surname>Hariharan</surname><given-names>N</given-names></name><name><surname>Sacchi</surname><given-names>V</given-names></name><name><surname>Truffa</surname><given-names>S</given-names></name><name><surname>Joyo</surname><given-names>A</given-names></name><name><surname>Voelkers</surname><given-names>M</given-names></name><name><surname>Alvarez</surname><given-names>R</given-names></name><name><surname>Sussman</surname><given-names>MA</given-names></name></person-group><article-title>Notch activation enhances lineage commitment and protective signaling in cardiac progenitor cells</article-title><source>Basic Res Cardiol</source><year>2015</year><volume>110</volume><fpage>29</fpage><pub-id pub-id-type="doi">10.1007/s00395-015-0488-3</pub-id><pub-id pub-id-type="pmid">25893875</pub-id></element-citation></ref><ref id="CR21"><label>21.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hildebrand</surname><given-names>D</given-names></name><name><surname>Uhle</surname><given-names>F</given-names></name><name><surname>Sahin</surname><given-names>D</given-names></name><name><surname>Krauser</surname><given-names>U</given-names></name><name><surname>Weigand</surname><given-names>MA</given-names></name><name><surname>Heeg</surname><given-names>K</given-names></name></person-group><article-title>The interplay of notch signaling and STAT3 in TLR-activated human primary monocytes</article-title><source>Front Cell Infect Microbiol</source><year>2018</year><volume>8</volume><fpage>241</fpage><pub-id pub-id-type="doi">10.3389/fcimb.2018.00241</pub-id><pub-id pub-id-type="pmid">30042932</pub-id></element-citation></ref><ref id="CR22"><label>22.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Hoffmann</surname><given-names>M</given-names></name><name><surname>Kleine-Weber</surname><given-names>H</given-names></name><name><surname>Schroeder</surname><given-names>S</given-names></name><name><surname>Krüger</surname><given-names>N</given-names></name><name><surname>Herrler</surname><given-names>T</given-names></name><name><surname>Erichsen</surname><given-names>S</given-names></name><name><surname>Schiergens</surname><given-names>TS</given-names></name><name><surname>Herrler</surname><given-names>G</given-names></name><name><surname>Wu</surname><given-names>NH</given-names></name><name><surname>Nitsche</surname><given-names>A</given-names></name><name><surname>Müller</surname><given-names>MA</given-names></name><name><surname>Drosten</surname><given-names>C</given-names></name><name><surname>Pöhlmann</surname><given-names>S</given-names></name></person-group><article-title>SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and Is blocked by a clinically proven protease inhibitor</article-title><source>Cell</source><year>2020</year><pub-id pub-id-type="doi">10.1016/j.cell.2020.02.052</pub-id><pub-id pub-id-type="pmid">32142651</pub-id></element-citation></ref><ref id="CR23"><label>23.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Huang</surname><given-names>C</given-names></name><name><surname>Wang</surname><given-names>Y</given-names></name><name><surname>Li</surname><given-names>X</given-names></name><name><surname>Ren</surname><given-names>L</given-names></name><name><surname>Zhao</surname><given-names>J</given-names></name><name><surname>Hu</surname><given-names>Y</given-names></name><name><surname>Zhang</surname><given-names>L</given-names></name><name><surname>Fan</surname><given-names>G</given-names></name><name><surname>Xu</surname><given-names>J</given-names></name><name><surname>Gu</surname><given-names>X</given-names></name><name><surname>Cheng</surname><given-names>Z</given-names></name><name><surname>Yu</surname><given-names>T</given-names></name><name><surname>Xia</surname><given-names>J</given-names></name><name><surname>Wei</surname><given-names>Y</given-names></name><name><surname>Wu</surname><given-names>W</given-names></name><name><surname>Xie</surname><given-names>X</given-names></name><name><surname>Yin</surname><given-names>W</given-names></name><name><surname>Li</surname><given-names>H</given-names></name><name><surname>Liu</surname><given-names>M</given-names></name><name><surname>Xiao</surname><given-names>Y</given-names></name><name><surname>Gao</surname><given-names>H</given-names></name><name><surname>Guo</surname><given-names>L</given-names></name><name><surname>Xie</surname><given-names>J</given-names></name><name><surname>Wang</surname><given-names>G</given-names></name><name><surname>Jiang</surname><given-names>R</given-names></name><name><surname>Gao</surname><given-names>Z</given-names></name><name><surname>Jin</surname><given-names>Q</given-names></name><name><surname>Wang</surname><given-names>J</given-names></name><name><surname>Cao</surname><given-names>B</given-names></name></person-group><article-title>Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China</article-title><source>Lancet</source><year>2020</year><volume>395</volume><fpage>497</fpage><lpage>506</lpage><pub-id pub-id-type="doi">10.1016/S0140-6736(20)30183-5</pub-id><pub-id pub-id-type="pmid">31986264</pub-id></element-citation></ref><ref id="CR24"><label>24.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ito</surname><given-names>T</given-names></name><name><surname>Allen</surname><given-names>RM</given-names></name><name><surname>Carson</surname><given-names>WF</given-names></name><name><surname>Schaller</surname><given-names>M</given-names></name><name><surname>Cavassani</surname><given-names>KA</given-names></name><name><surname>Hogaboam</surname><given-names>CM</given-names></name><name><surname>Lukacs</surname><given-names>NW</given-names></name><name><surname>Matsukawa</surname><given-names>A</given-names></name><name><surname>Kunkel</surname><given-names>SL</given-names></name></person-group><article-title>The critical role of Notch ligand Delta-like 1 in the pathogenesis of influenza A virus (H1N1) infection</article-title><source>PLoS Pathog</source><year>2011</year><volume>7</volume><fpage>e1002341</fpage><pub-id pub-id-type="doi">10.1371/journal.ppat.1002341</pub-id><pub-id pub-id-type="pmid">22072963</pub-id></element-citation></ref><ref id="CR25"><label>25.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Kyula</surname><given-names>JN</given-names></name><name><surname>Van Schaeybroeck</surname><given-names>S</given-names></name><name><surname>Doherty</surname><given-names>J</given-names></name><name><surname>Fenning</surname><given-names>CS</given-names></name><name><surname>Longley</surname><given-names>DB</given-names></name><name><surname>Johnston</surname><given-names>PG</given-names></name></person-group><article-title>Chemotherapy-induced activation of ADAM-17: a novel mechanism of drug resistance in colorectal cancer</article-title><source>Clin Cancer Res</source><year>2010</year><volume>16</volume><fpage>3378</fpage><lpage>3389</lpage><pub-id pub-id-type="doi">10.1158/1078-0432.CCR-10-0014</pub-id><pub-id pub-id-type="pmid">20570921</pub-id></element-citation></ref><ref id="CR26"><label>26.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lambert</surname><given-names>DW</given-names></name><name><surname>Yarski</surname><given-names>M</given-names></name><name><surname>Warner</surname><given-names>FJ</given-names></name><name><surname>Thornhill</surname><given-names>P</given-names></name><name><surname>Parkin</surname><given-names>ET</given-names></name><name><surname>Smith</surname><given-names>AI</given-names></name><name><surname>Hooper</surname><given-names>NM</given-names></name><name><surname>Turner</surname><given-names>AJ</given-names></name></person-group><article-title>Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2)</article-title><source>J Biol Chem</source><year>2005</year><volume>280</volume><fpage>30113</fpage><lpage>30119</lpage><pub-id pub-id-type="doi">10.1074/jbc.M505111200</pub-id><pub-id pub-id-type="pmid">15983030</pub-id></element-citation></ref><ref id="CR27"><label>27.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lei</surname><given-names>C</given-names></name><name><surname>Fu</surname><given-names>W</given-names></name><name><surname>Qian</surname><given-names>K</given-names></name><name><surname>Li</surname><given-names>T</given-names></name><name><surname>Zhang</surname><given-names>S</given-names></name><name><surname>Ding</surname><given-names>M</given-names></name><name><surname>Hu</surname><given-names>S</given-names></name></person-group><article-title>Potent neutralization of 2019 novel coronavirus by recombinant ACE2-Ig</article-title><source>Biorxiv</source><year>2020</year><pub-id pub-id-type="doi">10.1101/2020.02.01.929976</pub-id></element-citation></ref><ref id="CR28"><label>28.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Lukacs</surname><given-names>NW</given-names></name><name><surname>Smit</surname><given-names>JJ</given-names></name><name><surname>Schaller</surname><given-names>MA</given-names></name><name><surname>Lindell</surname><given-names>DM</given-names></name></person-group><article-title>Regulation of immunity to respiratory syncytial virus by dendritic cells, toll-like receptors, and notch</article-title><source>Viral Immunol</source><year>2008</year><volume>21</volume><fpage>115</fpage><lpage>122</lpage><pub-id pub-id-type="doi">10.1089/vim.2007.0110</pub-id><pub-id pub-id-type="pmid">18419253</pub-id></element-citation></ref><ref id="CR29"><label>29.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Molano</surname><given-names>FD</given-names></name><name><surname>Arevalo-Rodriguez</surname><given-names>I</given-names></name><name><surname>Roqué i Figuls</surname><given-names>M</given-names></name><name><surname>Montero Oleas</surname><given-names>N</given-names></name><name><surname>Nuvials</surname><given-names>X</given-names></name><name><surname>Zamora</surname><given-names>J</given-names></name></person-group><article-title>Levels of interleukin-6 in identifying severely ill adult patients with sepsis</article-title><source>Cochrane</source><year>2020</year><pub-id pub-id-type="doi">10.1002/14651858.CD011811</pub-id></element-citation></ref><ref id="CR30"><label>30.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Osborne</surname><given-names>BA</given-names></name><name><surname>Minter</surname><given-names>LM</given-names></name></person-group><article-title>Notch signalling during peripheral T-cell activation and differentiation</article-title><source>Nat Rev Immunol</source><year>2007</year><volume>7</volume><fpage>64</fpage><lpage>75</lpage><pub-id pub-id-type="doi">10.1038/nri1998</pub-id><pub-id pub-id-type="pmid">17170755</pub-id></element-citation></ref><ref id="CR31"><label>31.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Park</surname><given-names>JS</given-names></name><name><surname>Kim</surname><given-names>SH</given-names></name><name><surname>Kim</surname><given-names>K</given-names></name><name><surname>Jin</surname><given-names>CH</given-names></name><name><surname>Choi</surname><given-names>KY</given-names></name><name><surname>Jang</surname><given-names>J</given-names></name><name><surname>Choi</surname><given-names>Y</given-names></name><name><surname>Gwon</surname><given-names>AR</given-names></name><name><surname>Baik</surname><given-names>SH</given-names></name><name><surname>Yun</surname><given-names>UJ</given-names></name><name><surname>Chae</surname><given-names>SY</given-names></name><name><surname>Lee</surname><given-names>S</given-names></name><name><surname>Kang</surname><given-names>YM</given-names></name><name><surname>Lee</surname><given-names>KC</given-names></name><name><surname>Arumugam</surname><given-names>TV</given-names></name><name><surname>Mattson</surname><given-names>MP</given-names></name><name><surname>Park</surname><given-names>JH</given-names></name><name><surname>Jo</surname><given-names>DG</given-names></name></person-group><article-title>Inhibition of notch signalling ameliorates experimental inflammatory arthritis</article-title><source>Ann Rheum Dis</source><year>2015</year><volume>74</volume><fpage>267</fpage><lpage>274</lpage><pub-id pub-id-type="doi">10.1136/annrheumdis-2013-203467</pub-id><pub-id pub-id-type="pmid">24255545</pub-id></element-citation></ref><ref id="CR32"><label>32.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Patel</surname><given-names>VB</given-names></name><name><surname>Clarke</surname><given-names>N</given-names></name><name><surname>Wang</surname><given-names>Z</given-names></name><name><surname>Fan</surname><given-names>D</given-names></name><name><surname>Parajuli</surname><given-names>N</given-names></name><name><surname>Basu</surname><given-names>R</given-names></name><name><surname>Putko</surname><given-names>B</given-names></name><name><surname>Kassiri</surname><given-names>Z</given-names></name><name><surname>Turner</surname><given-names>AJ</given-names></name><name><surname>Oudit</surname><given-names>GY</given-names></name></person-group><article-title>Angiotensin II induced proteolytic cleavage of myocardial ACE2 is mediated by TACE/ADAM-17: a positive feedback mechanism in the RAS</article-title><source>J Mol Cell Cardiol</source><year>2014</year><volume>66</volume><fpage>167</fpage><lpage>176</lpage><pub-id pub-id-type="doi">10.1016/j.yjmcc.2013.11.017</pub-id><pub-id pub-id-type="pmid">24332999</pub-id></element-citation></ref><ref id="CR33"><label>33.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Paules</surname><given-names>CI</given-names></name><name><surname>Marston</surname><given-names>HD</given-names></name><name><surname>Fauci</surname><given-names>AS</given-names></name></person-group><article-title>Coronavirus infections-more than just the common cold</article-title><source>JAMA</source><year>2020</year><pub-id pub-id-type="doi">10.1001/jama.2020.0757</pub-id><pub-id pub-id-type="pmid">31971553</pub-id></element-citation></ref><ref id="CR34"><label>34.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Pei</surname><given-names>H</given-names></name><name><surname>Yu</surname><given-names>Q</given-names></name><name><surname>Xue</surname><given-names>Q</given-names></name><name><surname>Guo</surname><given-names>Y</given-names></name><name><surname>Sun</surname><given-names>L</given-names></name><name><surname>Hong</surname><given-names>Z</given-names></name><name><surname>Han</surname><given-names>H</given-names></name><name><surname>Gao</surname><given-names>E</given-names></name><name><surname>Qu</surname><given-names>Y</given-names></name><name><surname>Tao</surname><given-names>L</given-names></name></person-group><article-title>Notch1 cardioprotection in myocardial ischemia/reperfusion involves reduction of oxidative/nitrative stress</article-title><source>Basic Res Cardiol</source><year>2013</year><volume>108</volume><fpage>373</fpage><pub-id pub-id-type="doi">10.1007/s00395-013-0373-x</pub-id><pub-id pub-id-type="pmid">23989801</pub-id></element-citation></ref><ref id="CR35"><label>35.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Penninkilampi</surname><given-names>R</given-names></name><name><surname>Brothers</surname><given-names>HM</given-names></name><name><surname>Eslick</surname><given-names>GD</given-names></name></person-group><article-title>Pharmacological agents targeting γ-secretase increase risk of cancer and cognitive decline in alzheimer's disease patients: a systematic review and meta-analysis</article-title><source>J Alzheimers Dis</source><year>2016</year><volume>53</volume><fpage>1395</fpage><lpage>1404</lpage><pub-id pub-id-type="doi">10.3233/JAD-160275</pub-id><pub-id pub-id-type="pmid">27392862</pub-id></element-citation></ref><ref id="CR36"><label>36.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Qin</surname><given-names>C</given-names></name><name><surname>Zhou</surname><given-names>L</given-names></name><name><surname>Hu</surname><given-names>Z</given-names></name><name><surname>Zhang</surname><given-names>S</given-names></name><name><surname>Yang</surname><given-names>S</given-names></name><name><surname>Tao</surname><given-names>Y</given-names></name><name><surname>Xie</surname><given-names>C</given-names></name><name><surname>Ma</surname><given-names>K</given-names></name><name><surname>Shang</surname><given-names>K</given-names></name><name><surname>Wang</surname><given-names>W</given-names></name><name><surname>Tian</surname><given-names>DS</given-names></name></person-group><article-title>Dysregulation of immune response in patients with COVID-19 in Wuhan, China</article-title><source>Clin Infect Dis</source><year>2020</year><pub-id pub-id-type="doi">10.1093/cid/ciaa248</pub-id><pub-id pub-id-type="pmid">32255183</pub-id></element-citation></ref><ref id="CR37"><label>37.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Qin</surname><given-names>L</given-names></name><name><surname>Qiu</surname><given-names>KZ</given-names></name><name><surname>Hu</surname><given-names>CP</given-names></name><name><surname>Wu</surname><given-names>GJ</given-names></name><name><surname>Wang</surname><given-names>LL</given-names></name><name><surname>Tan</surname><given-names>YR</given-names></name></person-group><article-title>Bronchial epithelial cells promote the differentiation of Th2 lymphocytes in airway microenvironment through jagged/notch-1 signaling after RSV infection</article-title><source>Int Arch Allergy Immunol</source><year>2019</year><volume>179</volume><fpage>43</fpage><lpage>52</lpage><pub-id pub-id-type="doi">10.1159/000495581</pub-id><pub-id pub-id-type="pmid">30943513</pub-id></element-citation></ref><ref id="CR38"><label>38.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Qiu</surname><given-names>H</given-names></name><name><surname>Tang</surname><given-names>X</given-names></name><name><surname>Ma</surname><given-names>J</given-names></name><name><surname>Shaverdashvili</surname><given-names>K</given-names></name><name><surname>Zhang</surname><given-names>K</given-names></name><name><surname>Bedogni</surname><given-names>B</given-names></name></person-group><article-title>Notch1 autoactivation via transcriptional regulation of furin, which sustains notch1 signaling by processing notch1-activating proteases ADAM10 and membrane type 1 matrix metalloproteinase</article-title><source>Mol Cell Biol</source><year>2015</year><volume>35</volume><fpage>3622</fpage><lpage>3632</lpage><pub-id pub-id-type="doi">10.1128/MCB.00116-15</pub-id><pub-id pub-id-type="pmid">26283728</pub-id></element-citation></ref><ref id="CR39"><label>39.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Radojcic</surname><given-names>V</given-names></name><name><surname>Maillard</surname><given-names>I</given-names></name></person-group><article-title>Notch signaling and alloreactivity</article-title><source>Transplantation</source><year>2016</year><volume>100</volume><fpage>2593</fpage><lpage>2600</lpage><pub-id pub-id-type="doi">10.1097/TP.0000000000001468</pub-id><pub-id pub-id-type="pmid">27607530</pub-id></element-citation></ref><ref id="CR40"><label>40.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rapezzi</surname><given-names>C</given-names></name><name><surname>Ferrari</surname><given-names>R</given-names></name></person-group><article-title>The Cardiologist at the time of Coronavirus: a perfect storm</article-title><source>Eur Heart J.</source><year>2020</year><volume>41</volume><fpage>1320</fpage><lpage>1322</lpage><pub-id pub-id-type="doi">10.1093/eurheartj/ehaa233</pub-id><pub-id pub-id-type="pmid">32236465</pub-id></element-citation></ref><ref id="CR41"><label>41.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ren</surname><given-names>J</given-names></name><name><surname>Nie</surname><given-names>Y</given-names></name><name><surname>Lv</surname><given-names>M</given-names></name><name><surname>Shen</surname><given-names>S</given-names></name><name><surname>Tang</surname><given-names>R</given-names></name><name><surname>Xu</surname><given-names>Y</given-names></name><name><surname>Hou</surname><given-names>Y</given-names></name><name><surname>Zhao</surname><given-names>S</given-names></name><name><surname>Wang</surname><given-names>T</given-names></name></person-group><article-title>Estrogen upregulates MICA/B expression in human non-small cell lung cancer through the regulation of ADAM17</article-title><source>Cell Mol Immunol</source><year>2015</year><volume>12</volume><fpage>768</fpage><lpage>776</lpage><pub-id pub-id-type="doi">10.1038/cmi.2014.101</pub-id><pub-id pub-id-type="pmid">25363527</pub-id></element-citation></ref><ref id="CR42"><label>42.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Rizzo</surname><given-names>P</given-names></name><name><surname>Miele</surname><given-names>L</given-names></name><name><surname>Ferrari</surname><given-names>R</given-names></name></person-group><article-title>The notch pathway: a crossroad between the life and death of the endothelium</article-title><source>Eur Heart J</source><year>2013</year><volume>34</volume><fpage>2504</fpage><lpage>2509</lpage><pub-id pub-id-type="doi">10.1093/eurheartj/ehs141</pub-id><pub-id pub-id-type="pmid">22645188</pub-id></element-citation></ref><ref id="CR43"><label>43.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Ruan</surname><given-names>Q</given-names></name><name><surname>Yang</surname><given-names>K</given-names></name><name><surname>Wang</surname><given-names>W</given-names></name><name><surname>Jiang</surname><given-names>L</given-names></name><name><surname>Song</surname><given-names>J</given-names></name></person-group><article-title>Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan China</article-title><source>Intensive Care Med</source><year>2020</year><pub-id pub-id-type="doi">10.1007/s00134-020-05991-x</pub-id><pub-id pub-id-type="pmid">32253449</pub-id></element-citation></ref><ref id="CR44"><label>44.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schmieder</surname><given-names>RE</given-names></name></person-group><article-title>Mechanisms for the clinical benefits of angiotensin II receptor blockers</article-title><source>Am J Hypertens</source><year>2005</year><volume>18</volume><fpage>720</fpage><lpage>730</lpage><pub-id pub-id-type="doi">10.1016/j.amjhyper.2004.11.032</pub-id><pub-id pub-id-type="pmid">15882557</pub-id></element-citation></ref><ref id="CR45"><label>45.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schneider</surname><given-names>CS</given-names></name><name><surname>Xu</surname><given-names>Q</given-names></name><name><surname>Boylan</surname><given-names>NJ</given-names></name><name><surname>Chisholm</surname><given-names>J</given-names></name><name><surname>Tang</surname><given-names>BC</given-names></name><name><surname>Schuster</surname><given-names>BS</given-names></name><name><surname>Henning</surname><given-names>A</given-names></name><name><surname>Ensign</surname><given-names>LM</given-names></name><name><surname>Lee</surname><given-names>E</given-names></name><name><surname>Adstamongkonkul</surname><given-names>P</given-names></name><name><surname>Simons</surname><given-names>BW</given-names></name><name><surname>Wang</surname><given-names>SS</given-names></name><name><surname>Gong</surname><given-names>X</given-names></name><name><surname>Yu</surname><given-names>T</given-names></name><name><surname>Boyle</surname><given-names>MP</given-names></name><name><surname>Suk</surname><given-names>JS</given-names></name><name><surname>Hanes</surname><given-names>J</given-names></name></person-group><article-title>Nanoparticles that do not adhere to mucus provide uniform and long-lasting drug delivery to airways following inhalation</article-title><source>Sci Adv</source><year>2017</year><volume>3</volume><fpage>e1601556</fpage><pub-id pub-id-type="doi">10.1126/sciadv.1601556</pub-id><pub-id pub-id-type="pmid">28435870</pub-id></element-citation></ref><ref id="CR46"><label>46.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Schoeman</surname><given-names>D</given-names></name><name><surname>Fielding</surname><given-names>BC</given-names></name></person-group><article-title>Coronavirus envelope protein: current knowledge</article-title><source>Virol J</source><year>2019</year><volume>16</volume><fpage>69</fpage><pub-id pub-id-type="doi">10.1186/s12985-019-1182-0</pub-id><pub-id pub-id-type="pmid">31133031</pub-id></element-citation></ref><ref id="CR47"><label>47.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Shiryaev</surname><given-names>SA</given-names></name><name><surname>Remacle</surname><given-names>AG</given-names></name><name><surname>Ratnikov</surname><given-names>BI</given-names></name><name><surname>Nelson</surname><given-names>NA</given-names></name><name><surname>Savinov</surname><given-names>AY</given-names></name><name><surname>Wei</surname><given-names>G</given-names></name><name><surname>Bottini</surname><given-names>M</given-names></name><name><surname>Rega</surname><given-names>MF</given-names></name><name><surname>Parent</surname><given-names>A</given-names></name><name><surname>Desjardins</surname><given-names>R</given-names></name><name><surname>Fugere</surname><given-names>M</given-names></name><name><surname>Day</surname><given-names>R</given-names></name><name><surname>Sabet</surname><given-names>M</given-names></name><name><surname>Pellecchia</surname><given-names>M</given-names></name><name><surname>Liddington</surname><given-names>RC</given-names></name><name><surname>Smith</surname><given-names>JW</given-names></name><name><surname>Mustelin</surname><given-names>T</given-names></name><name><surname>Guiney</surname><given-names>DG</given-names></name><name><surname>Lebl</surname><given-names>M</given-names></name><name><surname>Strongin</surname><given-names>AY</given-names></name></person-group><article-title>Targeting host cell furin proprotein convertases as a therapeutic strategy against bacterial toxins and viral pathogens</article-title><source>J Biol Chem</source><year>2007</year><volume>282</volume><fpage>20847</fpage><lpage>20853</lpage><pub-id pub-id-type="doi">10.1074/jbc.M703847200</pub-id><pub-id pub-id-type="pmid">17537721</pub-id></element-citation></ref><ref id="CR48"><label>48.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Tian</surname><given-names>S</given-names></name><name><surname>Hu</surname><given-names>W</given-names></name><name><surname>Niu</surname><given-names>L</given-names></name><name><surname>Liu</surname><given-names>H</given-names></name><name><surname>Xu</surname><given-names>H</given-names></name><name><surname>Xiao</surname><given-names>SY</given-names></name></person-group><article-title>Pulmonary pathology of early phase 2019 novel coronavirus (COVID-19) pneumonia in two patients with lung cancer</article-title><source>J Thorac Oncol</source><year>2020</year><pub-id pub-id-type="doi">10.1016/j.jtho.2020.02.010</pub-id><pub-id pub-id-type="pmid">32114094</pub-id></element-citation></ref><ref id="CR49"><label>49.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Vieceli Dalla Sega</surname><given-names>F</given-names></name><name><surname>Fortini</surname><given-names>F</given-names></name><name><surname>Aquila</surname><given-names>G</given-names></name><name><surname>Campo</surname><given-names>G</given-names></name><name><surname>Vaccarezza</surname><given-names>M</given-names></name><name><surname>Rizzo</surname><given-names>P</given-names></name></person-group><article-title>Notch signaling regulates immune responses in atherosclerosis</article-title><source>Front Immunol</source><year>2019</year><volume>10</volume><fpage>1130</fpage><pub-id pub-id-type="doi">10.3389/fimmu.2019.01130</pub-id><pub-id pub-id-type="pmid">31191522</pub-id></element-citation></ref><ref id="CR50"><label>50.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Walls</surname><given-names>AC</given-names></name><name><surname>Park</surname><given-names>YJ</given-names></name><name><surname>Tortorici</surname><given-names>MA</given-names></name><name><surname>Wall</surname><given-names>A</given-names></name><name><surname>McGuire</surname><given-names>AT</given-names></name><name><surname>Veesler</surname><given-names>D</given-names></name></person-group><article-title>Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein</article-title><source>Cell</source><year>2020</year><pub-id pub-id-type="doi">10.1016/j.cell.2020.02.058</pub-id><pub-id pub-id-type="pmid">32155444</pub-id></element-citation></ref><ref id="CR51"><label>51.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>D</given-names></name><name><surname>Hu</surname><given-names>B</given-names></name><name><surname>Hu</surname><given-names>C</given-names></name><name><surname>Zhu</surname><given-names>F</given-names></name><name><surname>Liu</surname><given-names>X</given-names></name><name><surname>Zhang</surname><given-names>J</given-names></name><name><surname>Wang</surname><given-names>B</given-names></name><name><surname>Xiang</surname><given-names>H</given-names></name><name><surname>Cheng</surname><given-names>Z</given-names></name><name><surname>Xiong</surname><given-names>Y</given-names></name><name><surname>Zhao</surname><given-names>Y</given-names></name><name><surname>Li</surname><given-names>Y</given-names></name><name><surname>Wang</surname><given-names>X</given-names></name><name><surname>Peng</surname><given-names>Z</given-names></name></person-group><article-title>Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan. China</article-title><source>JAMA</source><year>2020</year><pub-id pub-id-type="doi">10.1001/jama.2020.1585</pub-id><pub-id pub-id-type="pmid">32259222</pub-id></element-citation></ref><ref id="CR52"><label>52.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Wongchana</surname><given-names>W</given-names></name><name><surname>Palaga</surname><given-names>T</given-names></name></person-group><article-title>Direct regulation of interleukin-6 expression by Notch signaling in macrophages</article-title><source>Cell Mol Immunol</source><year>2012</year><volume>9</volume><fpage>155</fpage><lpage>162</lpage><pub-id pub-id-type="doi">10.1038/cmi.2011.36</pub-id><pub-id pub-id-type="pmid">21983868</pub-id></element-citation></ref><ref id="CR53"><label>53.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zheng</surname><given-names>YY</given-names></name><name><surname>Ma</surname><given-names>YT</given-names></name><name><surname>Zhang</surname><given-names>JY</given-names></name><name><surname>Xie</surname><given-names>X</given-names></name></person-group><article-title>COVID-19 and the cardiovascular system</article-title><source>Nat Rev Cardiol</source><year>2020</year><pub-id pub-id-type="doi">10.1038/s41569-020-0360-5</pub-id><pub-id pub-id-type="pmid">32231330</pub-id></element-citation></ref><ref id="CR54"><label>54.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhou</surname><given-names>P</given-names></name><name><surname>Yang</surname><given-names>XL</given-names></name><name><surname>Wang</surname><given-names>XG</given-names></name><name><surname>Hu</surname><given-names>B</given-names></name><name><surname>Zhang</surname><given-names>L</given-names></name><name><surname>Zhang</surname><given-names>W</given-names></name><name><surname>Si</surname><given-names>HR</given-names></name><name><surname>Zhu</surname><given-names>Y</given-names></name><name><surname>Li</surname><given-names>B</given-names></name><name><surname>Huang</surname><given-names>CL</given-names></name><name><surname>Chen</surname><given-names>HD</given-names></name><name><surname>Chen</surname><given-names>J</given-names></name><name><surname>Luo</surname><given-names>Y</given-names></name><name><surname>Guo</surname><given-names>H</given-names></name><name><surname>Jiang</surname><given-names>RD</given-names></name><name><surname>Liu</surname><given-names>MQ</given-names></name><name><surname>Chen</surname><given-names>Y</given-names></name><name><surname>Shen</surname><given-names>XR</given-names></name><name><surname>Wang</surname><given-names>X</given-names></name><name><surname>Zheng</surname><given-names>XS</given-names></name><name><surname>Zhao</surname><given-names>K</given-names></name><name><surname>Chen</surname><given-names>QJ</given-names></name><name><surname>Deng</surname><given-names>F</given-names></name><name><surname>Liu</surname><given-names>LL</given-names></name><name><surname>Yan</surname><given-names>B</given-names></name><name><surname>Zhan</surname><given-names>FX</given-names></name><name><surname>Wang</surname><given-names>YY</given-names></name><name><surname>Xiao</surname><given-names>GF</given-names></name><name><surname>Shi</surname><given-names>ZL</given-names></name></person-group><article-title>A pneumonia outbreak associated with a new coronavirus of probable bat origin</article-title><source>Nature</source><year>2020</year><volume>579</volume><fpage>270</fpage><lpage>273</lpage><pub-id pub-id-type="doi">10.1038/s41586-020-2012-7</pub-id><pub-id pub-id-type="pmid">32015507</pub-id></element-citation></ref><ref id="CR55"><label>55.</label><element-citation publication-type="journal"><person-group person-group-type="author"><name><surname>Zhu</surname><given-names>N</given-names></name><name><surname>Zhang</surname><given-names>D</given-names></name><name><surname>Wang</surname><given-names>W</given-names></name><name><surname>Li</surname><given-names>X</given-names></name><name><surname>Yang</surname><given-names>B</given-names></name><name><surname>Song</surname><given-names>J</given-names></name><name><surname>Zhao</surname><given-names>X</given-names></name><name><surname>Huang</surname><given-names>B</given-names></name><name><surname>Shi</surname><given-names>W</given-names></name><name><surname>Lu</surname><given-names>R</given-names></name><name><surname>Niu</surname><given-names>P</given-names></name><name><surname>Zhan</surname><given-names>F</given-names></name><name><surname>Ma</surname><given-names>X</given-names></name><name><surname>Wang</surname><given-names>D</given-names></name><name><surname>Xu</surname><given-names>W</given-names></name><name><surname>Wu</surname><given-names>G</given-names></name><name><surname>Gao</surname><given-names>GF</given-names></name><name><surname>Tan</surname><given-names>W</given-names></name><collab>Team CNCIaR</collab></person-group><article-title>A Novel coronavirus from patients with pneumonia in China, 2019</article-title><source>N Engl J Med</source><year>2020</year><volume>382</volume><fpage>727</fpage><lpage>733</lpage><pub-id pub-id-type="doi">10.1056/NEJMoa2001017</pub-id><pub-id pub-id-type="pmid">31978945</pub-id></element-citation></ref></ref-list></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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