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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Tracking the transmission and evolution of MERS-CoV</title><author><name sortKey="Hui, David S" sort="Hui, David S" uniqKey="Hui D" first="David S" last="Hui">David S. Hui</name><affiliation><nlm:aff id="aff1">Department of Medicine and Therapeutics, and Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24055454</idno><idno type="pmc">7134991</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7134991</idno><idno type="RBID">PMC:7134991</idno><idno type="doi">10.1016/S0140-6736(13)61955-8</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000814</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000814</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Tracking the transmission and evolution of MERS-CoV</title><author><name sortKey="Hui, David S" sort="Hui, David S" uniqKey="Hui D" first="David S" last="Hui">David S. Hui</name><affiliation><nlm:aff id="aff1">Department of Medicine and Therapeutics, and Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China</nlm:aff></affiliation></author></analytic><series><title level="j">Lancet (London, England)</title><idno type="ISSN">0140-6736</idno><idno type="eISSN">1474-547X</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Zaki, Am" uniqKey="Zaki A">AM Zaki</name></author><author><name sortKey="Van Boheemen, S" uniqKey="Van Boheemen S">S van Boheemen</name></author><author><name sortKey="Bestebroer, Tm" uniqKey="Bestebroer T">TM Bestebroer</name></author><author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name></author><author><name sortKey="Fouchier, Ra" uniqKey="Fouchier R">RA Fouchier</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author><author><name sortKey="Zumla, Ai" uniqKey="Zumla A">AI Zumla</name></author><author><name sortKey="Al Hakeem, Rf" uniqKey="Al Hakeem R">RF Al-Hakeem</name></author><author><name sortKey="Al Rabeeah, Aa" uniqKey="Al Rabeeah A">AA Al-Rabeeah</name></author><author><name sortKey="Stephens, Gm" uniqKey="Stephens G">GM Stephens</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Assiri, A" uniqKey="Assiri A">A Assiri</name></author><author><name sortKey="Mcgeer, A" uniqKey="Mcgeer A">A McGeer</name></author><author><name sortKey="Perl, Tm" uniqKey="Perl T">TM Perl</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guery, B" uniqKey="Guery B">B Guery</name></author><author><name sortKey="Poissy, J" uniqKey="Poissy J">J Poissy</name></author><author><name sortKey="El Mansouf, L" uniqKey="El Mansouf L">L el Mansouf</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Memish, Z" uniqKey="Memish Z">Z Memish</name></author><author><name sortKey="Mishra, N" uniqKey="Mishra N">N Mishra</name></author><author><name sortKey="Olival, K" uniqKey="Olival K">K Olival</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reusken, Cb" uniqKey="Reusken C">CB Reusken</name></author><author><name sortKey="Haagmans, Bl" uniqKey="Haagmans B">BL Haagmans</name></author><author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Muller</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Cotten, M" uniqKey="Cotten M">M Cotten</name></author><author><name sortKey="Watson, Sj" uniqKey="Watson S">SJ Watson</name></author><author><name sortKey="Kellam, P" uniqKey="Kellam P">P Kellam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chim, Ss" uniqKey="Chim S">SS Chim</name></author><author><name sortKey="Tsui, Sk" uniqKey="Tsui S">SK Tsui</name></author><author><name sortKey="Chan, Kc" uniqKey="Chan K">KC Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chiu, Rw" uniqKey="Chiu R">RW Chiu</name></author><author><name sortKey="Chim, Ss" uniqKey="Chim S">SS Chim</name></author><author><name sortKey="Lo, Ym" uniqKey="Lo Y">YM Lo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guan, Y" uniqKey="Guan Y">Y Guan</name></author><author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name></author><author><name sortKey="Zheng, B" uniqKey="Zheng B">B Zheng</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ng, Ek" uniqKey="Ng E">EK Ng</name></author><author><name sortKey="Ng, Pc" uniqKey="Ng P">PC Ng</name></author><author><name sortKey="Hon, Kl" uniqKey="Hon K">KL Hon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ng, Ek" uniqKey="Ng E">EK Ng</name></author><author><name sortKey="Hui, Ds" uniqKey="Hui D">DS Hui</name></author><author><name sortKey="Chan, Kc" uniqKey="Chan K">KC Chan</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="discussion"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Lancet</journal-id><journal-id journal-id-type="iso-abbrev">Lancet</journal-id><journal-title-group><journal-title>Lancet (London, England)</journal-title></journal-title-group><issn pub-type="ppub">0140-6736</issn><issn pub-type="epub">1474-547X</issn><publisher><publisher-name>Hui. Open Access article distributed under the terms of CC BY-NC-ND. Published by Elsevier Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">24055454</article-id><article-id pub-id-type="pmc">7134991</article-id><article-id pub-id-type="publisher-id">S0140-6736(13)61955-8</article-id><article-id pub-id-type="doi">10.1016/S0140-6736(13)61955-8</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Tracking the transmission and evolution of MERS-CoV</article-title></title-group><contrib-group><contrib contrib-type="author" id="au10"><name><surname>Hui</surname><given-names>David S</given-names></name><email>dschui@cuhk.edu.hk</email><xref rid="aff1" ref-type="aff">a</xref></contrib></contrib-group><aff id="aff1"><label>a</label>Department of Medicine and Therapeutics, and Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China</aff><pub-date pub-type="pmc-release"><day>20</day><month>9</month><year>2013</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub" iso-8601-date="2013-12-20"><season>14-20 December</season><year>2013</year></pub-date><pub-date pub-type="epub"><day>20</day><month>9</month><year>2013</year></pub-date><volume>382</volume><issue>9909</issue><fpage>1962</fpage><lpage>1964</lpage><permissions><copyright-statement>© 2013 Hui. Open Access article distributed under the terms of CC BY-NC-ND</copyright-statement><copyright-year>2013</copyright-year><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><related-article related-article-type="article-reference" id="d32e289" ext-link-type="doi" xlink:href="10.1016/S0140-6736(13)61887-5"></related-article></article-meta></front><body><p id="para10">In 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in a patient who died of severe pneumonia in Saudi Arabia.<xref rid="bib1" ref-type="bibr"><sup>1</sup></xref> Although most cases confirmed so far in the Middle East have been sporadic with an unknown source of infection, human-to-human transmission has been reported in health-care and household settings.<xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib3" ref-type="bibr">3</xref>, <xref rid="bib4" ref-type="bibr">4</xref> However, the source of the virus and mode of disease transmission remain unknown despite detection of a small fragment of sequence identical to the EMC/2012 MERS-CoV in a <italic>Taphozous perforatus</italic> bat captured in Saudi Arabia<xref rid="bib5" ref-type="bibr"><sup>5</sup></xref> and reports of cross-reactive antibodies to MERS-CoV in dromedary camels in Oman and the Canary Islands.<xref rid="bib6" ref-type="bibr"><sup>6</sup></xref></p><p id="para20">A hospital outbreak of MERS in the eastern province of Saudi Arabia was previously described,<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref> with full genome analysis of four isolates of the Al-Hasa outbreak combined with five previously identified MERS-CoV genomes. The investigators estimated that the time of most recent common ancestor (tMRCA) was August, 2011 (95% highest posterior density [HPD] November, 2009 to April, 2012), and showed that the four viruses formed a monophyletic clade. The study provided a better understanding of the transmission of MERS-CoV within family clusters<xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib7" ref-type="bibr">7</xref> and in health-care settings.<xref rid="bib4" ref-type="bibr"><sup>4</sup></xref> Nevertheless, the four cases selected were closely linked epidemiologically within this outbreak involving four health-care facilities.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref></p><p id="para30">In <italic>The Lancet</italic>, Matthew Cotten and colleagues<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref> further describe the geographical distribution and phylogenetic relation of MERS-CoV infections across time in Saudi Arabia. This study represents the largest number of MERS-CoV genomes described so far, with 13 complete and eight partial genomes (30–95% genome coverage) from 21 clinical MERS samples taken from the Al-Hasa outbreak and four other sites in Saudi Arabia (Riyadh, Buraidah, Bisha, and Hafr-Al-Batin). Each of the sequences was derived directly from clinical specimens of patients and thus avoided any mutations that would be introduced by tissue culture passage. The authors report three distinct MERS-CoV genotypes, whereas phylogeographic analyses suggest that the MERS-CoV zoonotic reservoir is geographically dispersed. Furthermore, genetic diversity in the Al-Hasa cluster suggests that the hospital outbreak might have been caused by more than one virus introduction. The data obtained from clinical MERS samples from the Al-Hasa cluster and community outbreaks has recorded evolution of the MERS-CoV virus in this epidemic within Saudi Arabia, and the sequence variations also reveal remarkable multiple-tree clusters. The study has provided interesting data supporting circulation of MERS-CoV since the middle of 2011, with the estimated tMRCA as July, 2011 (95% HPD July, 2007 to June, 2012).<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref></p><p id="para40">Although the human exposures that result in infection remain unknown, this study has added the novel finding of three distinct MERS-CoV genotypes in Riyadh, with at least two distinct lineages probably circulating in Riyadh in October, 2012. Disease transmission patterns in the epidemic suggest both human-to-human transmission and sporadic zoonotic events. The current genome sequence set is not adequate to discriminate definitively between single or multiple zoonotic introductions, but the description of the pair of related genomes from Riyadh and Bisha and the description of cases in east and west Saudi Arabia in both major lineages of the tree suggest many zoonotic events. Overall, this is an interesting study that extends earlier findings.<xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib3" ref-type="bibr">3</xref> Although this report provides neither direct evidence of animal transmission nor the precise mechanism of transmission, the information is useful in tracing the source and transmission of MERS-CoV.<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref></p><p id="para50">There are some examples of the historical role and scientific value of molecular methods in tracing emerging severe acute respiratory infections. After the major outbreaks of SARS-CoV in 2003, researchers in many countries had applied molecular genome analysis to track the viral evolution and spread of the disease.<xref rid="bib9" ref-type="bibr">9</xref>, <xref rid="bib10" ref-type="bibr">10</xref>, <xref rid="bib11" ref-type="bibr">11</xref> PCR has provided the scientific basis for direct examination of clinical samples for evidence of infection. Similar to MERS-CoV, sequence variations were reported in SARS-CoV obtained from different patients in this epidemic.<xref rid="bib9" ref-type="bibr">9</xref>, <xref rid="bib10" ref-type="bibr">10</xref>, <xref rid="bib11" ref-type="bibr">11</xref> Cotten and colleagues<xref rid="bib8" ref-type="bibr"><sup>8</sup></xref> have effectively shown that sequence variations in the MERS-CoV genome can be applied as a powerful molecular method in tracing the route of transmission, when used in conjunction with standard epidemiology. Furthermore, using the publicly released full genomic sequences of SARS-CoV in 2003, various molecular detection methods based on RT-PCR were developed. Most of the diagnostic assays were initially focused on RNA extracted from nasopharyngeal aspirates, urine, and stools, but assays based on the analysis of RNA extracted from plasma and serum were later developed.<xref rid="bib12" ref-type="bibr">12</xref>, <xref rid="bib13" ref-type="bibr">13</xref> Such blood RNA assays (with one targeted at the nucleocapsid region and the other the polymerase region of the virus genome) allowed the more standardised quantitative expression of viral loads and became useful for early SARS diagnosis, with a detection rate of up to 80% during the first week of illness, when serology diagnosis of SARS was not sensitive at the early stage.<xref rid="bib12" ref-type="bibr">12</xref>, <xref rid="bib13" ref-type="bibr">13</xref> These quantitative systems, if available, might be useful for the early diagnosis of MERS-CoV and can provide viral load information that might facilitate prognostic assessments of an infected individual.</p><p id="para60">With the increasing number of sporadic cases of MERS in the Middle East, more research is needed into the mode of transmission and exposures responsible for the sporadic introductions of MERS-CoV into human populations. Development of rapid and reliable diagnostic assays is also urgently needed so that health authorities can take appropriate public health measures to interrupt disease transmission and contain the virus.</p><p id="para70"><fig id="f10"><graphic xlink:href="fx1_lrg"></graphic><permissions><copyright-statement>© 2013 Centre For Infections/Public Health England/Science Photo Library</copyright-statement><copyright-year>2013</copyright-year><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. 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