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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Emerging threats from zoonotic coronaviruses-from SARS and MERS to 2019-nCoV</title><author><name sortKey="Lee, Ping Ing" sort="Lee, Ping Ing" uniqKey="Lee P" first="Ping-Ing" last="Lee">Ping-Ing Lee</name><affiliation><nlm:aff id="aff1">Department of Pediatrics, National Taiwan University Children's Hospital and National Taiwan University College of Medicine, Taipei, Taiwan</nlm:aff></affiliation></author><author><name sortKey="Hsueh, Po Ren" sort="Hsueh, Po Ren" uniqKey="Hsueh P" first="Po-Ren" last="Hsueh">Po-Ren Hsueh</name><affiliation><nlm:aff id="aff2">Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32035811</idno><idno type="pmc">7102579</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102579</idno><idno type="RBID">PMC:7102579</idno><idno type="doi">10.1016/j.jmii.2020.02.001</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000722</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000722</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Emerging threats from zoonotic coronaviruses-from SARS and MERS to 2019-nCoV</title><author><name sortKey="Lee, Ping Ing" sort="Lee, Ping Ing" uniqKey="Lee P" first="Ping-Ing" last="Lee">Ping-Ing Lee</name><affiliation><nlm:aff id="aff1">Department of Pediatrics, National Taiwan University Children's Hospital and National Taiwan University College of Medicine, Taipei, Taiwan</nlm:aff></affiliation></author><author><name sortKey="Hsueh, Po Ren" sort="Hsueh, Po Ren" uniqKey="Hsueh P" first="Po-Ren" last="Hsueh">Po-Ren Hsueh</name><affiliation><nlm:aff id="aff2">Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan</nlm:aff></affiliation></author></analytic><series><title level="j">Journal of Microbiology, Immunology, and Infection</title><idno type="ISSN">1684-1182</idno><idno type="eISSN">1995-9133</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zhu, N" uniqKey="Zhu N">N. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">J Microbiol Immunol Infect</journal-id><journal-id journal-id-type="iso-abbrev">J Microbiol Immunol Infect</journal-id><journal-title-group><journal-title>Journal of Microbiology, Immunology, and Infection</journal-title></journal-title-group><issn pub-type="ppub">1684-1182</issn><issn pub-type="epub">1995-9133</issn><publisher><publisher-name>published by Elsevier for the Taiwan Society of Microbiology</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32035811</article-id><article-id pub-id-type="pmc">7102579</article-id><article-id pub-id-type="publisher-id">S1684-1182(20)30011-6</article-id><article-id pub-id-type="doi">10.1016/j.jmii.2020.02.001</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Emerging threats from zoonotic coronaviruses-from SARS and MERS to 2019-nCoV</article-title></title-group><contrib-group><contrib contrib-type="author" id="au1"><name><surname>Lee</surname><given-names>Ping-Ing</given-names></name><email>pinging@ntu.edu.tw</email><xref rid="aff1" ref-type="aff">a</xref><xref rid="cor1" ref-type="corresp">∗</xref></contrib><contrib contrib-type="author" id="au2"><name><surname>Hsueh</surname><given-names>Po-Ren</given-names></name><xref rid="aff2" ref-type="aff">b</xref><xref rid="aff3" ref-type="aff">c</xref></contrib></contrib-group><aff id="aff1"><label>a</label>Department of Pediatrics, National Taiwan University Children's Hospital and National Taiwan University College of Medicine, Taipei, Taiwan</aff><aff id="aff2"><label>b</label>Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan</aff><aff id="aff3"><label>c</label>Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan</aff><author-notes><corresp id="cor1"><label>∗</label>Corresponding author. Department of Pediatrics, National Taiwan University Children's Hospital, No.8, Chung Shan S. Rd., Taipei, 10041, Taiwan. <email>pinging@ntu.edu.tw</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>4</day><month>2</month><year>2020</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="epub"><day>4</day><month>2</month><year>2020</year></pub-date><elocation-id></elocation-id><history><date date-type="received"><day>1</day><month>2</month><year>2020</year></date><date date-type="accepted"><day>1</day><month>2</month><year>2020</year></date></history><permissions><copyright-statement>© 2020 Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC.</copyright-statement><copyright-year>2020</copyright-year><copyright-holder></copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions></article-meta></front><body><p id="p0010">Coronaviruses are enveloped RNA viruses that are widely detected in mammals and birds, and commonly denoted in etiologies of upper respiratory tract infections in humans.<xref rid="bib1" ref-type="bibr">1</xref>, <xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib3" ref-type="bibr">3</xref> Two potentially dangerous zoonotic coronaviruses have emerged in the past two decades. The severe acute respiratory syndrome coronavirus (SARS-CoV), originating from China, was responsible for the first outbreak that extended from 2002 to 2003. The second outbreak occurred in 2012 in the Middle East and was caused by the Middle East respiratory syndrome coronavirus (MERS-CoV).<xref rid="bib1" ref-type="bibr">1</xref>, <xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib3" ref-type="bibr">3</xref>, <xref rid="bib4" ref-type="bibr">4</xref></p><p id="p0015">A new strain of coronavirus, designated as the 2019 novel coronavirus (2019-nCoV), emerged during the third outbreak in Wuhan, China, at the end of 2019.<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref> Symptoms of pneumonia with unknown etiology were reported in several patients. The infection was epidemiologically linked to the Huanan seafood market in Wuhan.<xref rid="bib6" ref-type="bibr"><sup>6</sup></xref> Similar to the SARS-CoV and the MERS-CoV, bats have been denoted as the likely primary reservoirs of the 2019-nCoV based on its similarity to bat coronaviruses.<xref rid="bib7" ref-type="bibr"><sup>7</sup></xref> The intermediary reservoir is yet to be denoted.</p><p id="p0020">The pertinent and critical factor for an emerging virus is its pandemic potential. Efficient human-to-human transmission is a requirement for large-scale spread of a new virus. The proportion of patients with mild symptoms of illness is another important factor that determines our ability to identify infected individuals and to prevent the spread of virus. Identification of transmission chains and subsequent contact tracing are further complicated when several infected individuals remain asymptomatic or mildly symptomatic.<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref></p><p id="p0025">A key factor for efficient human-to-human transmission is the ability of the virus to attach to human cells. Coronaviruses use a spike protein for attachment to host cells.<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref> Apparently, the 2019-nCoV uses the same human angiotensin-converting enzyme 2 receptor as the SARS-CoV,<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref> whereas the MERS-CoV used dipeptidyl peptidase 4 (also known as CD26).<xref rid="bib9" ref-type="bibr"><sup>9</sup></xref></p><p id="p0030">An efficient human-to-human transmission involves multiples routes of transmission, including droplet transfer, direct contact, and indirect contact. A limited human-to-human transmission may require a high infective dose and a significantly close contact with an infected person as prerequisites (<xref rid="tbl1" ref-type="table">Table 1</xref>).<table-wrap position="float" id="tbl1"><label>Table 1</label><caption><p>Efficiency of animal virus-associated human-to-human transmission.</p></caption><alt-text id="alttext0010">Table 1</alt-text><table frame="hsides" rules="groups"><thead><tr><th>Efficiency</th><th>Infective dose</th><th>Pandemic potential</th><th>Example</th></tr></thead><tbody><tr><td>Efficient</td><td>Low</td><td>High</td><td>SARS-CoV, probably 2019-nCoV</td></tr><tr><td>Limited</td><td>High</td><td>Low</td><td>MERS-CoV</td></tr><tr><td>Very limited</td><td>Very high</td><td>Very low</td><td>Avian influenza virus</td></tr><tr><td>No</td><td>None</td><td>None</td><td>Japanese encephalitis virus</td></tr></tbody></table><table-wrap-foot><fn><p>SARS-CoV, severe acute respiratory syndrome coronavirus; 2019-nCoV, 2019 novel coronavirus; MERS-CoV, Middle East respiratory syndrome coronavirus.</p></fn></table-wrap-foot></table-wrap></p><p id="p0035">All three zoonotic coronavirus outbreaks in recent decades are associated with pneumonia in patients with severe illness. Available data suggest that the 2019-nCoV may be less pathogenic than the MERS-CoV and SARS-CoV (<xref rid="tbl2" ref-type="table">Table 2</xref>). However, the severity of the disease is not necessarily linked to its transmission efficiency and pandemic potential.<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref> A rapidly increasing number of 2019-nCoV-infected cases suggests that this virus may be transmitted effectively among humans, and mild illness may be quite common in infected individuals.<xref rid="bib1" ref-type="bibr"><sup>1</sup></xref><sup>,</sup><xref rid="bib2" ref-type="bibr"><sup>2</sup></xref><sup>,</sup><xref rid="bib5" ref-type="bibr"><sup>5</sup></xref><sup>,</sup><xref rid="bib6" ref-type="bibr"><sup>6</sup></xref> These two features confer a high pandemic potential to the 2019-nCoV (<xref rid="tbl2" ref-type="table">Table 2</xref>).<table-wrap position="float" id="tbl2"><label>Table 2</label><caption><p>Epidemiological and clinical characteristics of zoonotic coronaviruses.</p></caption><alt-text id="alttext0015">Table 2</alt-text><table frame="hsides" rules="groups"><thead><tr><th>Coronavirus</th><th>SARS-CoV</th><th>MERS-CoV</th><th>2019-nCoV</th></tr></thead><tbody><tr><td>Years of outbreak</td><td>2002–2003</td><td>2012–present</td><td>2019–present</td></tr><tr><td>Primary reservoir</td><td>Bat</td><td>Bat</td><td>Bat</td></tr><tr><td>Intermediary reservoir</td><td>Civet cat</td><td>Camel</td><td>Unknown</td></tr><tr><td>Human-to-human transmission</td><td>Efficient</td><td>Limited</td><td>Possibly efficient</td></tr><tr><td>Pandemic potential</td><td>Yes</td><td>No</td><td>Yes</td></tr><tr><td>Contained</td><td>Yes</td><td>No</td><td>No, efforts ongoing</td></tr><tr><td>Incubation period</td><td>2–10 days</td><td>2–14 days</td><td>1–14 days</td></tr><tr><td>Pneumonia</td><td>Very common</td><td>Common</td><td>Common</td></tr><tr><td>Fatality rate</td><td>9.5%</td><td>34.4%</td><td>2–4% in confirmed cases to date</td></tr></tbody></table><table-wrap-foot><fn><p>SARS-CoV, severe acute respiratory syndrome coronavirus; MERS-CoV, Middle East respiratory syndrome coronavirus; 2019-nCoV, 2019 novel coronavirus.</p></fn></table-wrap-foot></table-wrap></p><p id="p0040">The next important factor to consider for the 2019-nCoV outbreak is our ability to contain the spread of this new virus. There was a lag of three months between the commencement of the SARS epidemic and the initiation of investigation by healthcare officials in 2003 in China.<xref rid="bib10" ref-type="bibr"><sup>10</sup></xref> Consequently, the infection spread to approximately 8100 people in 29 countries and resulted in 774 deaths.<xref rid="bib10" ref-type="bibr"><sup>10</sup></xref> Since mild illness is uncommon in SARS infection and infected individuals are easily identifiable, SARS could be contained effectively and eradicated without vaccination or effective antiviral therapy.<xref rid="bib10" ref-type="bibr"><sup>10</sup></xref> Currently, there are a limited number of studies from China that investigate the efficacy and potential of lopinavir/ritonavir (Kaletra), a combination of protease inhibitors used to treat and prevent HIV/AIDS, in the treatment of 2019-nCoV infection.<xref rid="bib11" ref-type="bibr"><sup>11</sup></xref> Other agents, including nucleoside analogues, neuraminidase inhibitors, remdesivir, umifenovir (arbidol), tenofovir disoproxil (TDF), and lamivudine (3TC), along with several Chinese traditional medicines, are reported as viable options for antiviral treatment of human pathogenic coronavirus.<xref rid="bib11" ref-type="bibr"><sup>11</sup></xref> Clinical efficacy of remdesivir for the treatment of the first US case of pneumonia caused by 2019-nCoV was recently reported.<xref rid="bib12" ref-type="bibr"><sup>12</sup></xref> However, these data are derived from preliminary stages of studies and are insufficient to support the implementation for clinical use in treatment of 2019-nCoV infection.<xref rid="bib11" ref-type="bibr"><sup>11</sup></xref><sup>,</sup><xref rid="bib12" ref-type="bibr"><sup>12</sup></xref></p><p id="p0045">The severe lack of information during the initial stage of the 2019-nCoV outbreak posed challenges to and complicated the containment of the infection in specific limited areas. A higher proportion of mild 2019-nCoV infections facilitates rapid spreading of the virus. Present efforts for containment may not be completely effective. 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