Middle East respiratory syndrome
Identifieur interne : 001383 ( Pmc/Corpus ); précédent : 001382; suivant : 001384Middle East respiratory syndrome
Auteurs : Ziad A. Memish ; Stanley Perlman ; Maria D. Van Kerkhove ; Alimuddin ZumlaSource :
- Lancet (London, England) [ 0140-6736 ] ; 2020.
Abstract
The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen that was first identified in humans in Saudi Arabia and Jordan in 2012. Intermittent sporadic cases, community clusters, and nosocomial outbreaks of MERS-CoV continue to occur. Between April 2012 and December 2019, 2499 laboratory-confirmed cases of MERS-CoV infection, including 858 deaths (34·3% mortality) were reported from 27 countries to WHO, the majority of which were reported by Saudi Arabia (2106 cases, 780 deaths). Large outbreaks of human-to-human transmission have occurred, the largest in Riyadh and Jeddah in 2014 and in South Korea in 2015. MERS-CoV remains a high-threat pathogen identified by WHO as a priority pathogen because it causes severe disease that has a high mortality rate, epidemic potential, and no medical countermeasures. This Seminar provides an update on the current knowledge and perspectives on MERS epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, management, infection control, development of new therapeutics and vaccines, and highlights unanswered questions and priorities for research, improved management, and prevention.
Url:
DOI: 10.1016/S0140-6736(19)33221-0
PubMed: 32145185
PubMed Central: 7155742
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Middle East respiratory syndrome</title><author><name sortKey="Memish, Ziad A" sort="Memish, Ziad A" uniqKey="Memish Z" first="Ziad A" last="Memish">Ziad A. Memish</name><affiliation><nlm:aff id="aff1">College of Medicine, Alfaisal University, Riyadh, Saudi Arabia</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Research Center, King Saud Medical City Ministry of Health, Riyadh, Saudi Arabia</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA</nlm:aff></affiliation></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><affiliation><nlm:aff id="aff4">Department of Microbiology and Immunology, and Department of Pediatrics, University of Iowa, Iowa City, IA, USA</nlm:aff></affiliation></author><author><name sortKey="Van Kerkhove, Maria D" sort="Van Kerkhove, Maria D" uniqKey="Van Kerkhove M" first="Maria D" last="Van Kerkhove">Maria D. Van Kerkhove</name><affiliation><nlm:aff id="aff5">Infectious Hazards Management, Health Emergencies Programme, World Health Organization, Geneva, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Zumla, Alimuddin" sort="Zumla, Alimuddin" uniqKey="Zumla A" first="Alimuddin" last="Zumla">Alimuddin Zumla</name><affiliation><nlm:aff id="aff6">Department of Infection, Division of Infection and Immunity, Centre for Clinical Microbiology, University College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="aff7">National Institute for Health Research Biomedical Research Centre, University College London Hospitals, London, UK</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32145185</idno><idno type="pmc">7155742</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155742</idno><idno type="RBID">PMC:7155742</idno><idno type="doi">10.1016/S0140-6736(19)33221-0</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">001383</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001383</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Middle East respiratory syndrome</title><author><name sortKey="Memish, Ziad A" sort="Memish, Ziad A" uniqKey="Memish Z" first="Ziad A" last="Memish">Ziad A. Memish</name><affiliation><nlm:aff id="aff1">College of Medicine, Alfaisal University, Riyadh, Saudi Arabia</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Research Center, King Saud Medical City Ministry of Health, Riyadh, Saudi Arabia</nlm:aff></affiliation><affiliation><nlm:aff id="aff3">Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA</nlm:aff></affiliation></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name><affiliation><nlm:aff id="aff4">Department of Microbiology and Immunology, and Department of Pediatrics, University of Iowa, Iowa City, IA, USA</nlm:aff></affiliation></author><author><name sortKey="Van Kerkhove, Maria D" sort="Van Kerkhove, Maria D" uniqKey="Van Kerkhove M" first="Maria D" last="Van Kerkhove">Maria D. Van Kerkhove</name><affiliation><nlm:aff id="aff5">Infectious Hazards Management, Health Emergencies Programme, World Health Organization, Geneva, Switzerland</nlm:aff></affiliation></author><author><name sortKey="Zumla, Alimuddin" sort="Zumla, Alimuddin" uniqKey="Zumla A" first="Alimuddin" last="Zumla">Alimuddin Zumla</name><affiliation><nlm:aff id="aff6">Department of Infection, Division of Infection and Immunity, Centre for Clinical Microbiology, University College London, London, UK</nlm:aff></affiliation><affiliation><nlm:aff id="aff7">National Institute for Health Research Biomedical Research Centre, University College London Hospitals, London, UK</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="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><p>The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen that was first identified in humans in Saudi Arabia and Jordan in 2012. Intermittent sporadic cases, community clusters, and nosocomial outbreaks of MERS-CoV continue to occur. Between April 2012 and December 2019, 2499 laboratory-confirmed cases of MERS-CoV infection, including 858 deaths (34·3% mortality) were reported from 27 countries to WHO, the majority of which were reported by Saudi Arabia (2106 cases, 780 deaths). Large outbreaks of human-to-human transmission have occurred, the largest in Riyadh and Jeddah in 2014 and in South Korea in 2015. MERS-CoV remains a high-threat pathogen identified by WHO as a priority pathogen because it causes severe disease that has a high mortality rate, epidemic potential, and no medical countermeasures. This Seminar provides an update on the current knowledge and perspectives on MERS epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, management, infection control, development of new therapeutics and vaccines, and highlights unanswered questions and priorities for research, improved management, and prevention.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name></author><author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name></author><author><name sortKey="Osterhaus, Ad" uniqKey="Osterhaus A">AD Osterhaus</name></author><author><name sortKey="Stohr, K" uniqKey="Stohr K">K Stöhr</name></author></analytic></biblStruct><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="Hijawi, B" uniqKey="Hijawi B">B Hijawi</name></author><author><name sortKey="Abdallat, M" uniqKey="Abdallat M">M Abdallat</name></author><author><name sortKey="Sayaydeh, A" uniqKey="Sayaydeh A">A Sayaydeh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name></author><author><name sortKey="Kellam, P" uniqKey="Kellam P">P Kellam</name></author><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="El Kafrawy, Sa" uniqKey="El Kafrawy S">SA El-Kafrawy</name></author><author><name sortKey="Corman, Vm" uniqKey="Corman V">VM Corman</name></author><author><name sortKey="Tolah, Am" uniqKey="Tolah A">AM Tolah</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zumla, A" uniqKey="Zumla A">A Zumla</name></author><author><name sortKey="Hui, Ds" uniqKey="Hui D">DS Hui</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S Perlman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Kh" uniqKey="Kim K">KH Kim</name></author><author><name sortKey="Tandi, Te" uniqKey="Tandi T">TE Tandi</name></author><author><name sortKey="Choi, Jw" uniqKey="Choi J">JW Choi</name></author><author><name sortKey="Moon, Jm" uniqKey="Moon J">JM Moon</name></author><author><name sortKey="Kim, Ms" uniqKey="Kim M">MS Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oh, Md" uniqKey="Oh M">MD Oh</name></author><author><name sortKey="Park, Wb" uniqKey="Park W">WB Park</name></author><author><name sortKey="Park, Sw" uniqKey="Park S">SW Park</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></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Masters, Ps" uniqKey="Masters P">PS Masters</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S Perlman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Raj, Vs" uniqKey="Raj V">VS Raj</name></author><author><name sortKey="Mou, H" uniqKey="Mou H">H Mou</name></author><author><name sortKey="Smits, Sl" uniqKey="Smits S">SL Smits</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Walls, Ac" uniqKey="Walls A">AC Walls</name></author><author><name sortKey="Tortorici, Ma" uniqKey="Tortorici M">MA Tortorici</name></author><author><name sortKey="Bosch, Bj" uniqKey="Bosch B">BJ Bosch</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yuan, Y" uniqKey="Yuan Y">Y Yuan</name></author><author><name sortKey="Cao, D" uniqKey="Cao D">D Cao</name></author><author><name sortKey="Zhang, Y" uniqKey="Zhang Y">Y Zhang</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fehr, Ar" uniqKey="Fehr A">AR Fehr</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S Perlman</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Conzade, R" uniqKey="Conzade R">R Conzade</name></author><author><name sortKey="Grant, R" uniqKey="Grant R">R Grant</name></author><author><name sortKey="Malik, Mr" uniqKey="Malik M">MR Malik</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hui, Ds" uniqKey="Hui D">DS Hui</name></author><author><name sortKey="Azhar, Ei" uniqKey="Azhar E">EI Azhar</name></author><author><name sortKey="Kim, Yj" uniqKey="Kim Y">YJ Kim</name></author><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author><author><name sortKey="Oh, Md" uniqKey="Oh M">MD Oh</name></author><author><name sortKey="Zumla, A" uniqKey="Zumla A">A Zumla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kandeil, A" uniqKey="Kandeil A">A Kandeil</name></author><author><name sortKey="Gomaa, M" uniqKey="Gomaa M">M Gomaa</name></author><author><name sortKey="Nageh, A" uniqKey="Nageh A">A Nageh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Reusken, Cb" uniqKey="Reusken C">CB Reusken</name></author><author><name sortKey="Ababneh, M" uniqKey="Ababneh M">M Ababneh</name></author><author><name sortKey="Raj, Vs" uniqKey="Raj V">VS Raj</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Azhar, Ei" uniqKey="Azhar E">EI Azhar</name></author><author><name sortKey="El Kafrawy, Sa" uniqKey="El Kafrawy S">SA El-Kafrawy</name></author><author><name sortKey="Farraj, Sa" uniqKey="Farraj S">SA Farraj</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Haagmans, Bl" uniqKey="Haagmans B">BL Haagmans</name></author><author><name sortKey="Al Dhahiry, Sh" uniqKey="Al Dhahiry S">SH Al Dhahiry</name></author><author><name sortKey="Reusken, Cb" uniqKey="Reusken C">CB Reusken</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Paden, Cr" uniqKey="Paden C">CR Paden</name></author><author><name sortKey="Yusof, M" uniqKey="Yusof M">M Yusof</name></author><author><name sortKey="Al Hammadi, Zm" uniqKey="Al Hammadi Z">ZM Al Hammadi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Adney, Dr" uniqKey="Adney D">DR Adney</name></author><author><name sortKey="Van Doremalen, N" uniqKey="Van Doremalen N">N van Doremalen</name></author><author><name sortKey="Brown, Vr" uniqKey="Brown V">VR Brown</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Khalafalla, Ai" uniqKey="Khalafalla A">AI Khalafalla</name></author><author><name sortKey="Lu, X" uniqKey="Lu X">X Lu</name></author><author><name sortKey="Al Mubarak, Ai" uniqKey="Al Mubarak A">AI Al-Mubarak</name></author><author><name sortKey="Dalab, Ah" uniqKey="Dalab A">AH Dalab</name></author><author><name sortKey="Al Busadah, Ka" uniqKey="Al Busadah K">KA Al-Busadah</name></author><author><name sortKey="Erdman, Dd" uniqKey="Erdman D">DD Erdman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sikkema, Rs" uniqKey="Sikkema R">RS Sikkema</name></author><author><name sortKey="Farag, E" uniqKey="Farag E">E Farag</name></author><author><name sortKey="Islam, M" uniqKey="Islam M">M Islam</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sabir, Js" uniqKey="Sabir J">JS Sabir</name></author><author><name sortKey="Lam, Tt" uniqKey="Lam T">TT Lam</name></author><author><name sortKey="Ahmed, Mm" uniqKey="Ahmed M">MM Ahmed</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Ji" uniqKey="Kim J">JI Kim</name></author><author><name sortKey="Park, S" uniqKey="Park S">S Park</name></author><author><name sortKey="Bae, Jy" uniqKey="Bae J">JY Bae</name></author><author><name sortKey="Park, Ms" uniqKey="Park M">MS Park</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Elkholy, Aa" uniqKey="Elkholy A">AA Elkholy</name></author><author><name sortKey="Grant, R" uniqKey="Grant R">R Grant</name></author><author><name sortKey="Assiri, A" uniqKey="Assiri A">A Assiri</name></author><author><name sortKey="Elhakim, M" uniqKey="Elhakim M">M Elhakim</name></author><author><name sortKey="Malik, Mr" uniqKey="Malik M">MR Malik</name></author><author><name sortKey="Van Kerkhove, Md" uniqKey="Van Kerkhove M">MD Van Kerkhove</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Hammadi, Zm" uniqKey="Al Hammadi Z">ZM Al Hammadi</name></author><author><name sortKey="Chu, Dk" uniqKey="Chu D">DK Chu</name></author><author><name sortKey="Eltahir, Ym" uniqKey="Eltahir Y">YM Eltahir</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alraddadi, Bm" uniqKey="Alraddadi B">BM Alraddadi</name></author><author><name sortKey="Al Salmi, Hs" uniqKey="Al Salmi H">HS Al-Salmi</name></author><author><name sortKey="Jacobs Slifka, K" uniqKey="Jacobs Slifka K">K Jacobs-Slifka</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Farag, Ea" uniqKey="Farag E">EA Farag</name></author><author><name sortKey="Reusken, Cb" uniqKey="Reusken C">CB Reusken</name></author><author><name sortKey="Haagmans, Bl" uniqKey="Haagmans B">BL Haagmans</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kasem, S" uniqKey="Kasem S">S Kasem</name></author><author><name sortKey="Qasim, I" uniqKey="Qasim I">I Qasim</name></author><author><name sortKey="Al Hufofi, A" uniqKey="Al Hufofi A">A Al-Hufofi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Muhairi, Sa" uniqKey="Muhairi S">SA Muhairi</name></author><author><name sortKey="Hosani, Fa" uniqKey="Hosani F">FA Hosani</name></author><author><name sortKey="Eltahir, Ym" uniqKey="Eltahir Y">YM Eltahir</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, J" uniqKey="Zhou J">J Zhou</name></author><author><name sortKey="Li, C" uniqKey="Li C">C Li</name></author><author><name sortKey="Zhao, G" uniqKey="Zhao G">G Zhao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bernard Stoecklin, S" uniqKey="Bernard Stoecklin S">S Bernard-Stoecklin</name></author><author><name sortKey="Nikolay, B" uniqKey="Nikolay B">B Nikolay</name></author><author><name sortKey="Assiri, A" uniqKey="Assiri A">A Assiri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Choi, S" uniqKey="Choi S">S Choi</name></author><author><name sortKey="Jung, E" uniqKey="Jung E">E Jung</name></author><author><name sortKey="Choi, By" uniqKey="Choi B">BY Choi</name></author><author><name sortKey="Hur, Yj" uniqKey="Hur Y">YJ Hur</name></author><author><name sortKey="Ki, M" uniqKey="Ki M">M Ki</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="Alanazi, Kh" uniqKey="Alanazi K">KH Alanazi</name></author><author><name sortKey="Killerby, Me" uniqKey="Killerby M">ME Killerby</name></author><author><name sortKey="Biggs, Hm" uniqKey="Biggs H">HM Biggs</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Amer, H" uniqKey="Amer H">H Amer</name></author><author><name sortKey="Alqahtani, As" uniqKey="Alqahtani A">AS Alqahtani</name></author><author><name sortKey="Alzoman, H" uniqKey="Alzoman H">H Alzoman</name></author><author><name sortKey="Aljerian, N" uniqKey="Aljerian N">N Aljerian</name></author><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kang, Ck" uniqKey="Kang C">CK Kang</name></author><author><name sortKey="Song, Kh" uniqKey="Song K">KH Song</name></author><author><name sortKey="Choe, Pg" uniqKey="Choe P">PG Choe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alsaad, Ko" uniqKey="Alsaad K">KO Alsaad</name></author><author><name sortKey="Hajeer, Ah" uniqKey="Hajeer A">AH Hajeer</name></author><author><name sortKey="Al Balwi, M" uniqKey="Al Balwi M">M Al Balwi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ng, Dl" uniqKey="Ng D">DL Ng</name></author><author><name sortKey="Al Hosani, F" uniqKey="Al Hosani F">F Al Hosani</name></author><author><name sortKey="Keating, Mk" uniqKey="Keating M">MK Keating</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Yeung, Ml" uniqKey="Yeung M">ML Yeung</name></author><author><name sortKey="Yao, Y" uniqKey="Yao Y">Y Yao</name></author><author><name sortKey="Jia, L" uniqKey="Jia L">L Jia</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Corman, Vm" uniqKey="Corman V">VM Corman</name></author><author><name sortKey="Albarrak, Am" uniqKey="Albarrak A">AM Albarrak</name></author><author><name sortKey="Omrani, As" uniqKey="Omrani A">AS Omrani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Widagdo, W" uniqKey="Widagdo W">W Widagdo</name></author><author><name sortKey="Sooksawasdi Na Ayudhya, S" uniqKey="Sooksawasdi Na Ayudhya S">S Sooksawasdi Na Ayudhya</name></author><author><name sortKey="Hundie, Gb" uniqKey="Hundie G">GB Hundie</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Leist, Sr" uniqKey="Leist S">SR Leist</name></author><author><name sortKey="Cockrell, As" uniqKey="Cockrell A">AS Cockrell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Channappanavar, R" uniqKey="Channappanavar R">R Channappanavar</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S Perlman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cameron, Mj" uniqKey="Cameron M">MJ Cameron</name></author><author><name sortKey="Ran, L" uniqKey="Ran L">L Ran</name></author><author><name sortKey="Xu, L" uniqKey="Xu L">L Xu</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chu, H" uniqKey="Chu H">H Chu</name></author><author><name sortKey="Zhou, J" uniqKey="Zhou J">J Zhou</name></author><author><name sortKey="Wong, Bh" uniqKey="Wong B">BH Wong</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lau, Sk" uniqKey="Lau S">SK Lau</name></author><author><name sortKey="Lau, Cc" uniqKey="Lau C">CC Lau</name></author><author><name sortKey="Chan, Kh" uniqKey="Chan K">KH Chan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, J" uniqKey="Zhou J">J Zhou</name></author><author><name sortKey="Chu, H" uniqKey="Chu H">H Chu</name></author><author><name sortKey="Li, C" uniqKey="Li C">C Li</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Shin, Hs" uniqKey="Shin H">HS Shin</name></author><author><name sortKey="Kim, Y" uniqKey="Kim Y">Y Kim</name></author><author><name sortKey="Kim, G" uniqKey="Kim G">G Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name></author><author><name sortKey="Meyer, B" uniqKey="Meyer B">B Meyer</name></author><author><name sortKey="Muller, Ma" uniqKey="Muller M">MA Müller</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, J" uniqKey="Zhao J">J Zhao</name></author><author><name sortKey="Alshukairi, An" uniqKey="Alshukairi A">AN Alshukairi</name></author><author><name sortKey="Baharoon, Sa" uniqKey="Baharoon S">SA Baharoon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alshukairi, An" uniqKey="Alshukairi A">AN Alshukairi</name></author><author><name sortKey="Khalid, I" uniqKey="Khalid I">I Khalid</name></author><author><name sortKey="Ahmed, Wa" uniqKey="Ahmed W">WA Ahmed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Ym" uniqKey="Arabi Y">YM Arabi</name></author><author><name sortKey="Balkhy, Hh" uniqKey="Balkhy H">HH Balkhy</name></author><author><name sortKey="Hayden, Fg" uniqKey="Hayden F">FG Hayden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cauchemez, S" uniqKey="Cauchemez S">S Cauchemez</name></author><author><name sortKey="Fraser, C" uniqKey="Fraser C">C Fraser</name></author><author><name sortKey="Van Kerkhove, Md" uniqKey="Van Kerkhove M">MD Van Kerkhove</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Breban, R" uniqKey="Breban R">R Breban</name></author><author><name sortKey="Riou, J" uniqKey="Riou J">J Riou</name></author><author><name sortKey="Fontanet, A" uniqKey="Fontanet A">A Fontanet</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Sh" uniqKey="Kim S">SH Kim</name></author><author><name sortKey="Ko, Jh" uniqKey="Ko J">JH Ko</name></author><author><name sortKey="Park, Ge" uniqKey="Park G">GE Park</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Drosten, C" uniqKey="Drosten C">C Drosten</name></author><author><name sortKey="Seilmaier, M" uniqKey="Seilmaier M">M Seilmaier</name></author><author><name sortKey="Corman, Vm" uniqKey="Corman V">VM Corman</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Grant, R" uniqKey="Grant R">R Grant</name></author><author><name sortKey="Malik, Mr" uniqKey="Malik M">MR Malik</name></author><author><name sortKey="Elkholy, A" uniqKey="Elkholy A">A Elkholy</name></author><author><name sortKey="Van Kerkhove, Md" uniqKey="Van Kerkhove M">MD Van Kerkhove</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Kim, Je" uniqKey="Kim J">JE Kim</name></author><author><name sortKey="Heo, Jh" uniqKey="Heo J">JH Heo</name></author><author><name sortKey="Kim, Ho" uniqKey="Kim H">HO Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alfaraj, Sh" uniqKey="Alfaraj S">SH Alfaraj</name></author><author><name sortKey="Al Tawfiq, Ja" uniqKey="Al Tawfiq J">JA Al-Tawfiq</name></author><author><name sortKey="Altuwaijri, Ta" uniqKey="Altuwaijri T">TA Altuwaijri</name></author><author><name sortKey="Alanazi, M" uniqKey="Alanazi M">M Alanazi</name></author><author><name sortKey="Alzahrani, N" uniqKey="Alzahrani N">N Alzahrani</name></author><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hui, Ds" uniqKey="Hui D">DS Hui</name></author><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author><author><name sortKey="Zumla, A" uniqKey="Zumla A">A Zumla</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Tawfiq, Ja" uniqKey="Al Tawfiq J">JA Al-Tawfiq</name></author><author><name sortKey="Kattan, Rf" uniqKey="Kattan R">RF Kattan</name></author><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alfaraj, Sh" uniqKey="Alfaraj S">SH Alfaraj</name></author><author><name sortKey="Al Tawfiq, Ja" uniqKey="Al Tawfiq J">JA Al-Tawfiq</name></author><author><name sortKey="Altuwaijri, Ta" uniqKey="Altuwaijri T">TA Altuwaijri</name></author><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author><author><name sortKey="Al Tawfiq, Ja" uniqKey="Al Tawfiq J">JA Al-Tawfiq</name></author><author><name sortKey="Assiri, A" uniqKey="Assiri A">A Assiri</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mobaraki, K" uniqKey="Mobaraki K">K Mobaraki</name></author><author><name sortKey="Ahmadzadeh, J" uniqKey="Ahmadzadeh J">J Ahmadzadeh</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alfaraj, Sh" uniqKey="Alfaraj S">SH Alfaraj</name></author><author><name sortKey="Al Tawfiq, Ja" uniqKey="Al Tawfiq J">JA Al-Tawfiq</name></author><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author><author><name sortKey="Al Tawfiq, Ja" uniqKey="Al Tawfiq J">JA Al-Tawfiq</name></author><author><name sortKey="Makhdoom, Hq" uniqKey="Makhdoom H">HQ Makhdoom</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oh, Md" uniqKey="Oh M">MD Oh</name></author><author><name sortKey="Park, Wb" uniqKey="Park W">WB Park</name></author><author><name sortKey="Choe, Pg" uniqKey="Choe P">PG Choe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bermingham, A" uniqKey="Bermingham A">A Bermingham</name></author><author><name sortKey="Chand, Ma" uniqKey="Chand M">MA Chand</name></author><author><name sortKey="Brown, Cs" uniqKey="Brown C">CS Brown</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alfaraj, Sh" uniqKey="Alfaraj S">SH Alfaraj</name></author><author><name sortKey="Al Tawfiq, Ja" uniqKey="Al Tawfiq J">JA Al-Tawfiq</name></author><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Kelly Cirino, C" uniqKey="Kelly Cirino C">C Kelly-Cirino</name></author><author><name sortKey="Mazzola, Lt" uniqKey="Mazzola L">LT Mazzola</name></author><author><name sortKey="Chua, A" uniqKey="Chua A">A Chua</name></author><author><name sortKey="Oxenford, Cj" uniqKey="Oxenford C">CJ Oxenford</name></author><author><name sortKey="Van Kerkhove, Md" uniqKey="Van Kerkhove M">MD Van Kerkhove</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Frans, G" uniqKey="Frans G">G Frans</name></author><author><name sortKey="Beuselinck, K" uniqKey="Beuselinck K">K Beuselinck</name></author><author><name sortKey="Peeters, B" uniqKey="Peeters B">B Peeters</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Huang, P" uniqKey="Huang P">P Huang</name></author><author><name sortKey="Wang, H" uniqKey="Wang H">H Wang</name></author><author><name sortKey="Cao, Z" uniqKey="Cao Z">Z Cao</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hashem, Am" uniqKey="Hashem A">AM Hashem</name></author><author><name sortKey="Al Amri, Ss" uniqKey="Al Amri S">SS Al-Amri</name></author><author><name sortKey="Al Subhi, Tl" uniqKey="Al Subhi T">TL Al-Subhi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Park, Sw" uniqKey="Park S">SW Park</name></author><author><name sortKey="Perera, Ra" uniqKey="Perera R">RA Perera</name></author><author><name sortKey="Choe, Pg" uniqKey="Choe P">PG Choe</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Perera, Ra" uniqKey="Perera R">RA Perera</name></author><author><name sortKey="Wang, P" uniqKey="Wang P">P Wang</name></author><author><name sortKey="Gomaa, Mr" uniqKey="Gomaa M">MR Gomaa</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Okba, Nma" uniqKey="Okba N">NMA Okba</name></author><author><name sortKey="Raj, Vs" uniqKey="Raj V">VS Raj</name></author><author><name sortKey="Widjaja, I" uniqKey="Widjaja I">I Widjaja</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Das, Km" uniqKey="Das K">KM Das</name></author><author><name sortKey="Lee, Ey" uniqKey="Lee E">EY Lee</name></author><author><name sortKey="Al Jawder, Se" uniqKey="Al Jawder S">SE Al Jawder</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Das, Km" uniqKey="Das K">KM Das</name></author><author><name sortKey="Lee, Ey" uniqKey="Lee E">EY Lee</name></author><author><name sortKey="Langer, Rd" uniqKey="Langer R">RD Langer</name></author><author><name sortKey="Larsson, Sg" uniqKey="Larsson S">SG Larsson</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ajlan, Am" uniqKey="Ajlan A">AM Ajlan</name></author><author><name sortKey="Ahyad, Ra" uniqKey="Ahyad R">RA Ahyad</name></author><author><name sortKey="Jamjoom, Lg" uniqKey="Jamjoom L">LG Jamjoom</name></author><author><name sortKey="Alharthy, A" uniqKey="Alharthy A">A Alharthy</name></author><author><name sortKey="Madani, Ta" uniqKey="Madani T">TA Madani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Das, Km" uniqKey="Das K">KM Das</name></author><author><name sortKey="Lee, Ey" uniqKey="Lee E">EY Lee</name></author><author><name sortKey="Enani, Ma" uniqKey="Enani M">MA Enani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Das, Km" uniqKey="Das K">KM Das</name></author><author><name sortKey="Lee, Ey" uniqKey="Lee E">EY Lee</name></author><author><name sortKey="Singh, R" uniqKey="Singh R">R Singh</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Momattin, H" uniqKey="Momattin H">H Momattin</name></author><author><name sortKey="Al Ali, Ay" uniqKey="Al Ali A">AY Al-Ali</name></author><author><name sortKey="Al Tawfiq, Ja" uniqKey="Al Tawfiq J">JA Al-Tawfiq</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Y" uniqKey="Arabi Y">Y Arabi</name></author><author><name sortKey="Balkhy, H" uniqKey="Balkhy H">H Balkhy</name></author><author><name sortKey="Hajeer, Ah" uniqKey="Hajeer A">AH Hajeer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Ym" uniqKey="Arabi Y">YM Arabi</name></author><author><name sortKey="Alothman, A" uniqKey="Alothman A">A Alothman</name></author><author><name sortKey="Balkhy, Hh" uniqKey="Balkhy H">HH Balkhy</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Ym" uniqKey="Arabi Y">YM Arabi</name></author><author><name sortKey="Mandourah, Y" uniqKey="Mandourah Y">Y Mandourah</name></author><author><name sortKey="Al Hameed, F" uniqKey="Al Hameed F">F Al-Hameed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Behzadi, Ma" uniqKey="Behzadi M">MA Behzadi</name></author><author><name sortKey="Leyva Grado, Vh" uniqKey="Leyva Grado V">VH Leyva-Grado</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Beigel, Jh" uniqKey="Beigel J">JH Beigel</name></author><author><name sortKey="Nam, Hh" uniqKey="Nam H">HH Nam</name></author><author><name sortKey="Adams, Pl" uniqKey="Adams P">PL Adams</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rabaan, Aa" uniqKey="Rabaan A">AA Rabaan</name></author><author><name sortKey="Alahmed, Sh" uniqKey="Alahmed S">SH Alahmed</name></author><author><name sortKey="Bazzi, Am" uniqKey="Bazzi A">AM Bazzi</name></author><author><name sortKey="Alhani, Hm" uniqKey="Alhani H">HM Alhani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, Y" uniqKey="Zhou Y">Y Zhou</name></author><author><name sortKey="Yang, Y" uniqKey="Yang Y">Y Yang</name></author><author><name sortKey="Huang, J" uniqKey="Huang J">J Huang</name></author><author><name sortKey="Jiang, S" uniqKey="Jiang S">S Jiang</name></author><author><name sortKey="Du, L" uniqKey="Du L">L Du</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zumla, A" uniqKey="Zumla A">A Zumla</name></author><author><name sortKey="Chan, Jf" uniqKey="Chan J">JF Chan</name></author><author><name sortKey="Azhar, Ei" uniqKey="Azhar E">EI Azhar</name></author><author><name sortKey="Hui, Ds" uniqKey="Hui D">DS Hui</name></author><author><name sortKey="Yuen, Ky" uniqKey="Yuen K">KY Yuen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhao, J" uniqKey="Zhao J">J Zhao</name></author><author><name sortKey="Perera, Ra" uniqKey="Perera R">RA Perera</name></author><author><name sortKey="Kayali, G" uniqKey="Kayali G">G Kayali</name></author><author><name sortKey="Meyerholz, D" uniqKey="Meyerholz D">D Meyerholz</name></author><author><name sortKey="Perlman, S" uniqKey="Perlman S">S Perlman</name></author><author><name sortKey="Peiris, M" uniqKey="Peiris M">M Peiris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ko, Jh" uniqKey="Ko J">JH Ko</name></author><author><name sortKey="Seok, H" uniqKey="Seok H">H Seok</name></author><author><name sortKey="Cho, Sy" uniqKey="Cho S">SY Cho</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Arabi, Ym" uniqKey="Arabi Y">YM Arabi</name></author><author><name sortKey="Deeb, Am" uniqKey="Deeb A">AM Deeb</name></author><author><name sortKey="Al Hameed, F" uniqKey="Al Hameed F">F Al-Hameed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alraddadi, Bm" uniqKey="Alraddadi B">BM Alraddadi</name></author><author><name sortKey="Qushmaq, I" uniqKey="Qushmaq I">I Qushmaq</name></author><author><name sortKey="Al Hameed, Fm" uniqKey="Al Hameed F">FM Al-Hameed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stalin Raj, V" uniqKey="Stalin Raj V">V Stalin Raj</name></author><author><name sortKey="Okba, Nma" uniqKey="Okba N">NMA Okba</name></author><author><name sortKey="Gutierrez Alvarez, J" uniqKey="Gutierrez Alvarez J">J Gutierrez-Alvarez</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Wang, L" uniqKey="Wang L">L Wang</name></author><author><name sortKey="Shi, W" uniqKey="Shi W">W Shi</name></author><author><name sortKey="Chappell, Jd" uniqKey="Chappell J">JD Chappell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Widjaja, I" uniqKey="Widjaja I">I Widjaja</name></author><author><name sortKey="Wang, C" uniqKey="Wang C">C Wang</name></author><author><name sortKey="Van Haperen, R" uniqKey="Van Haperen R">R van Haperen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, Sm" uniqKey="Lee S">SM Lee</name></author><author><name sortKey="Kang, Ws" uniqKey="Kang W">WS Kang</name></author><author><name sortKey="Cho, Ar" uniqKey="Cho A">AR Cho</name></author><author><name sortKey="Kim, T" uniqKey="Kim T">T Kim</name></author><author><name sortKey="Park, Jk" uniqKey="Park J">JK Park</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ahmed, Ae" uniqKey="Ahmed A">AE Ahmed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Park, Je" uniqKey="Park J">JE Park</name></author><author><name sortKey="Jung, S" uniqKey="Jung S">S Jung</name></author><author><name sortKey="Kim, A" uniqKey="Kim A">A Kim</name></author><author><name sortKey="Park, Je" uniqKey="Park J">JE Park</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Rahman, A" uniqKey="Rahman A">A Rahman</name></author><author><name sortKey="Sarkar, A" uniqKey="Sarkar A">A Sarkar</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sha, J" uniqKey="Sha J">J Sha</name></author><author><name sortKey="Li, Y" uniqKey="Li Y">Y Li</name></author><author><name sortKey="Chen, X" uniqKey="Chen X">X Chen</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Seys, Ljm" uniqKey="Seys L">LJM Seys</name></author><author><name sortKey="Widagdo, W" uniqKey="Widagdo W">W Widagdo</name></author><author><name sortKey="Verhamme, Fm" uniqKey="Verhamme F">FM Verhamme</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Batawi, S" uniqKey="Batawi S">S Batawi</name></author><author><name sortKey="Tarazan, N" uniqKey="Tarazan N">N Tarazan</name></author><author><name sortKey="Al Raddadi, R" uniqKey="Al Raddadi R">R Al-Raddadi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Ngai, Jc" uniqKey="Ngai J">JC Ngai</name></author><author><name sortKey="Ko, Fw" uniqKey="Ko F">FW Ko</name></author><author><name sortKey="Ng, Ss" uniqKey="Ng S">SS Ng</name></author><author><name sortKey="To, Kw" uniqKey="To K">KW To</name></author><author><name sortKey="Tong, M" uniqKey="Tong M">M Tong</name></author><author><name sortKey="Hui, Ds" uniqKey="Hui D">DS Hui</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Schindewolf, C" uniqKey="Schindewolf C">C Schindewolf</name></author><author><name sortKey="Menachery, Vd" uniqKey="Menachery V">VD Menachery</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hemida, Mg" uniqKey="Hemida M">MG Hemida</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hemida, Mg" uniqKey="Hemida M">MG Hemida</name></author><author><name sortKey="Alnaeem, A" uniqKey="Alnaeem A">A Alnaeem</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Park, S" uniqKey="Park S">S Park</name></author><author><name sortKey="Park, Jy" uniqKey="Park J">JY Park</name></author><author><name sortKey="Song, Y" uniqKey="Song Y">Y Song</name></author><author><name sortKey="How, Sh" uniqKey="How S">SH How</name></author><author><name sortKey="Jung, Ks" uniqKey="Jung K">KS Jung</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zumla, A" uniqKey="Zumla A">A Zumla</name></author><author><name sortKey="Dar, O" uniqKey="Dar O">O Dar</name></author><author><name sortKey="Kock, R" uniqKey="Kock R">R Kock</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kirchdoerfer, Rn" uniqKey="Kirchdoerfer R">RN Kirchdoerfer</name></author><author><name sortKey="Ward, Ab" uniqKey="Ward A">AB Ward</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Chu, Dkw" uniqKey="Chu D">DKW Chu</name></author><author><name sortKey="Hui, Kpy" uniqKey="Hui K">KPY Hui</name></author><author><name sortKey="Perera, R" uniqKey="Perera R">R Perera</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lamers, Mm" uniqKey="Lamers M">MM Lamers</name></author><author><name sortKey="Raj, Vs" uniqKey="Raj V">VS Raj</name></author><author><name sortKey="Shafei, M" uniqKey="Shafei M">M Shafei</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Xie, Q" uniqKey="Xie Q">Q Xie</name></author><author><name sortKey="Cao, Y" uniqKey="Cao Y">Y Cao</name></author><author><name sortKey="Su, J" uniqKey="Su J">J Su</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Knoops, K" uniqKey="Knoops K">K Knoops</name></author><author><name sortKey="Kikkert, M" uniqKey="Kikkert M">M Kikkert</name></author><author><name sortKey="Worm, Sh" uniqKey="Worm S">SH Worm</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Amer, H" uniqKey="Amer H">H Amer</name></author><author><name sortKey="Alqahtani, As" uniqKey="Alqahtani A">AS Alqahtani</name></author><author><name sortKey="Alaklobi, F" uniqKey="Alaklobi F">F Alaklobi</name></author><author><name sortKey="Altayeb, J" uniqKey="Altayeb J">J Altayeb</name></author><author><name sortKey="Memish, Za" uniqKey="Memish Z">ZA Memish</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Al Abdallat, Mm" uniqKey="Al Abdallat M">MM Al-Abdallat</name></author><author><name sortKey="Payne, Dc" uniqKey="Payne D">DC Payne</name></author><author><name sortKey="Alqasrawi, S" uniqKey="Alqasrawi S">S Alqasrawi</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alenazi, Th" uniqKey="Alenazi T">TH Alenazi</name></author><author><name sortKey="Al Arbash, H" uniqKey="Al Arbash H">H Al Arbash</name></author><author><name sortKey="El Saed, A" uniqKey="El Saed A">A El-Saed</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hui, Ds" uniqKey="Hui D">DS Hui</name></author><author><name sortKey="Peiris, M" uniqKey="Peiris M">M Peiris</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Nam, Hs" uniqKey="Nam H">HS Nam</name></author><author><name sortKey="Park, Jw" uniqKey="Park J">JW Park</name></author><author><name sortKey="Ki, M" uniqKey="Ki M">M Ki</name></author><author><name sortKey="Yeon, My" uniqKey="Yeon M">MY Yeon</name></author><author><name sortKey="Kim, J" uniqKey="Kim J">J Kim</name></author><author><name sortKey="Kim, Sw" uniqKey="Kim S">SW Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Oboho, Ik" uniqKey="Oboho I">IK Oboho</name></author><author><name sortKey="Tomczyk, Sm" uniqKey="Tomczyk S">SM Tomczyk</name></author><author><name sortKey="Al Asmari, Am" uniqKey="Al Asmari A">AM Al-Asmari</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Hunter, Jc" uniqKey="Hunter J">JC Hunter</name></author><author><name sortKey="Nguyen, D" uniqKey="Nguyen D">D Nguyen</name></author><author><name sortKey="Aden, B" uniqKey="Aden B">B Aden</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Jo, S" uniqKey="Jo S">S Jo</name></author><author><name sortKey="Kim, H" uniqKey="Kim H">H Kim</name></author><author><name sortKey="Kim, S" uniqKey="Kim S">S Kim</name></author><author><name sortKey="Shin, Dh" uniqKey="Shin D">DH Shin</name></author><author><name sortKey="Kim, Ms" uniqKey="Kim M">MS Kim</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Mustafa, S" uniqKey="Mustafa S">S Mustafa</name></author><author><name sortKey="Balkhy, H" uniqKey="Balkhy H">H Balkhy</name></author><author><name sortKey="Gabere, Mn" uniqKey="Gabere M">MN Gabere</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Agostini, Ml" uniqKey="Agostini M">ML Agostini</name></author><author><name sortKey="Pruijssers, Aj" uniqKey="Pruijssers A">AJ Pruijssers</name></author><author><name sortKey="Chappell, Jd" uniqKey="Chappell J">JD Chappell</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Sheahan, Tp" uniqKey="Sheahan T">TP Sheahan</name></author><author><name sortKey="Sims, Ac" uniqKey="Sims A">AC Sims</name></author><author><name sortKey="Graham, Rl" uniqKey="Graham R">RL Graham</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Taylor, R" uniqKey="Taylor R">R Taylor</name></author><author><name sortKey="Kotian, P" uniqKey="Kotian P">P Kotian</name></author><author><name sortKey="Warren, T" uniqKey="Warren T">T Warren</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="review-article"><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>Elsevier Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">32145185</article-id><article-id pub-id-type="pmc">7155742</article-id><article-id pub-id-type="publisher-id">S0140-6736(19)33221-0</article-id><article-id pub-id-type="doi">10.1016/S0140-6736(19)33221-0</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Middle East respiratory syndrome</article-title></title-group><contrib-group><contrib contrib-type="author" id="au10"><name><surname>Memish</surname><given-names>Ziad A</given-names></name><degrees>Prof</degrees><degrees>FRCP</degrees><xref rid="aff1" ref-type="aff">a</xref><xref rid="aff2" ref-type="aff">b</xref><xref rid="aff3" ref-type="aff">c</xref></contrib><contrib contrib-type="author" id="au20"><name><surname>Perlman</surname><given-names>Stanley</given-names></name><degrees>Prof</degrees><degrees>PhD</degrees><xref rid="aff4" ref-type="aff">d</xref></contrib><contrib contrib-type="author" id="au30"><name><surname>Van Kerkhove</surname><given-names>Maria D</given-names></name><degrees>PhD</degrees><xref rid="aff5" ref-type="aff">e</xref></contrib><contrib contrib-type="author" id="au40"><name><surname>Zumla</surname><given-names>Alimuddin</given-names></name><degrees>Prof</degrees><degrees>FRCP</degrees><email>a.zumla@ucl.ac.uk</email><xref rid="aff6" ref-type="aff">f</xref><xref rid="aff7" ref-type="aff">g</xref><xref rid="cor1" ref-type="corresp">*</xref></contrib></contrib-group><aff id="aff1"><label>a</label>College of Medicine, Alfaisal University, Riyadh, Saudi Arabia</aff><aff id="aff2"><label>b</label>Research Center, King Saud Medical City Ministry of Health, Riyadh, Saudi Arabia</aff><aff id="aff3"><label>c</label>Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA, USA</aff><aff id="aff4"><label>d</label>Department of Microbiology and Immunology, and Department of Pediatrics, University of Iowa, Iowa City, IA, USA</aff><aff id="aff5"><label>e</label>Infectious Hazards Management, Health Emergencies Programme, World Health Organization, Geneva, Switzerland</aff><aff id="aff6"><label>f</label>Department of Infection, Division of Infection and Immunity, Centre for Clinical Microbiology, University College London, London, UK</aff><aff id="aff7"><label>g</label>National Institute for Health Research Biomedical Research Centre, University College London Hospitals, London, UK</aff><author-notes><corresp id="cor1"><label>*</label>Correspondence to: Prof Sir Alimuddin Zumla, Department of Infection, Division of Infection and Immunity, Centre for Clinical Microbiology, University College London, London, NW3 OPE, UK <email>a.zumla@ucl.ac.uk</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>4</day><month>3</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="ppub" iso-8601-date="2020-04-03"><season>28 March-3 April</season><year>2020</year></pub-date><pub-date pub-type="epub"><day>4</day><month>3</month><year>2020</year></pub-date><volume>395</volume><issue>10229</issue><fpage>1063</fpage><lpage>1077</lpage><permissions><copyright-statement>© 2020 Elsevier Ltd. All rights reserved.</copyright-statement><copyright-year>2020</copyright-year><copyright-holder>Elsevier Ltd</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><abstract id="ceab10"><title>Summary</title><p>The Middle East respiratory syndrome coronavirus (MERS-CoV) is a lethal zoonotic pathogen that was first identified in humans in Saudi Arabia and Jordan in 2012. Intermittent sporadic cases, community clusters, and nosocomial outbreaks of MERS-CoV continue to occur. Between April 2012 and December 2019, 2499 laboratory-confirmed cases of MERS-CoV infection, including 858 deaths (34·3% mortality) were reported from 27 countries to WHO, the majority of which were reported by Saudi Arabia (2106 cases, 780 deaths). Large outbreaks of human-to-human transmission have occurred, the largest in Riyadh and Jeddah in 2014 and in South Korea in 2015. MERS-CoV remains a high-threat pathogen identified by WHO as a priority pathogen because it causes severe disease that has a high mortality rate, epidemic potential, and no medical countermeasures. This Seminar provides an update on the current knowledge and perspectives on MERS epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, management, infection control, development of new therapeutics and vaccines, and highlights unanswered questions and priorities for research, improved management, and prevention.</p></abstract></article-meta></front><body><sec id="cesec10"><title>Introduction</title><p id="para1370">During the past 17 years three lethal zoonotic diseases of humans caused by novel coronaviruses, severe acute repiratory syndrome (SARS) in November, 2002,<xref rid="bib1" ref-type="bibr"><sup>1</sup></xref> Middle East respiratory syndrome (MERS) in April, 2012,<xref rid="bib2" ref-type="bibr"><sup>2</sup></xref> and more recently coronavirus disease (COVID-19) in December, 2019.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref> All three causative coronaviruses, respectively, SARS-CoV, MERS-CoV, and SARS-related coronavirus-2 (SARS-CoV-2) have focused the attention of global public health authorities and are listed in the WHO Blueprint list for priority pathogens<xref rid="bib4" ref-type="bibr"><sup>4</sup></xref> because of their pandemic potential, threat to global health security, and the absence of any effective treatments.</p><p id="para1380">SARS-CoV was first identified in humans in Guangdong, China, in November, 2002 and subsequently spread rapidly worldwide to 29 countries, resulting in 8098 human SARS cases with 774 deaths (9·6% mortality).<xref rid="bib1" ref-type="bibr">1</xref>, <xref rid="bib5" ref-type="bibr">5</xref> The SARS epidemic ended abruptly in July, 2003,<xref rid="bib1" ref-type="bibr"><sup>1</sup></xref> and no human cases of SARS have been detected over the past 15 years. MERS-CoV was first identified as causing human disease when it was isolated from a lung sample of an adult patient who was admitted at a hospital in Jeddah, Saudi Arabia, with severe pneumonia and died of multiorgan failure.<xref rid="bib6" ref-type="bibr"><sup>6</sup></xref> A retrospective study then linked MERS-CoV to a hospital outbreak in April, 2012, in Jordan.<xref rid="bib7" ref-type="bibr"><sup>7</sup></xref> MERS-CoV is considered a zoonotic pathogen, with MERS-CoV-infected dromedary camels being the animal source of infection to humans.<xref rid="bib8" ref-type="bibr">8</xref>, <xref rid="bib9" ref-type="bibr">9</xref></p><p id="para1390">Unlike SARS-CoV, which was contained within a year of emerging, MERS-CoV continues to circulate and cause human disease with intermittent sporadic cases, community clusters, and nosocomial outbreaks in the Middle East with considerable risk of spreading globally.<xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib10" ref-type="bibr">10</xref> Several outbreaks of human-to-human MERS-CoV transmission have occurred, the largest outside the Middle East occurring in South Korea in 2015.<xref rid="bib11" ref-type="bibr">11</xref>, <xref rid="bib12" ref-type="bibr">12</xref> This outbreak was associated with substantial morbidity and mortality, as well as having substantial economic, social, and health security effects.<xref rid="bib12" ref-type="bibr"><sup>12</sup></xref></p><p id="para1400">SARS-CoV-2 (initially named 2019-nCoV) was detected in December 2019 after sequencing of clinical samples from a cluster of patients in Wuhan, China who developed pneumonia of unknown cause.<xref rid="bib13" ref-type="bibr"><sup>13</sup></xref> This outbreak is rapidly evolving and as of March 3, 2020 there have been 88 948 laboratory confirmed cases of COVID-19, with 3043 deaths (3·4% mortality). Outside China, there have been 8774 cases reported from 64 countries with 128 deaths.<xref rid="bib3" ref-type="bibr"><sup>3</sup></xref></p><p id="para1410">This Seminar reviews current knowledge and provides an update on MERS-CoV epidemiology, virology, mode of transmission, pathogenesis, diagnosis, clinical features, management, infection control, and development of new therapeutics and vaccines, and also highlights unanswered questions and priorities for research, improved management, and prevention.</p></sec><sec id="cesec20"><title>Virology</title><p id="para1420">MERS-CoV, SARS-CoV, and SARS-CoV-2, are members of the <italic>Coronaviridae</italic> family of the order Nidovirales. Other human coronaviruses generally cause mild respiratory infections (eg, HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1). MERS-CoV, like SARS-CoV and SARS-CoV-2, can cause highly lethal disease in humans. MERS-CoV is a large single-strand positive-sense RNA virus (<xref rid="fig1" ref-type="fig">figure 1</xref>).<xref rid="bib14" ref-type="bibr">14</xref>, <xref rid="bib15" ref-type="bibr">15</xref>, <xref rid="bib16" ref-type="bibr">16</xref>, <xref rid="bib17" ref-type="bibr">17</xref>, <xref rid="bib18" ref-type="bibr">18</xref> The 30–31 kb coronavirus genome encodes a large number of proteins, which might confer versatility in adapting to new environments and enhance cross-species transmission. MERS-CoV has four structural proteins: spike (S) protein, envelope (E)protein, membrane (M) protein, and nucleocapsid (N) protein. The S protein is a type I transmembrane glycoprotein located as a trimer on the virus surface and consists of S1 and S2 subunits. It has crucial roles in binding, fusion, and entry into host cells. The S1 subunit has a receptor binding domain that binds to the host cellular receptor dipeptidyl peptidase 4 (DPP4). The S2 subunit has two regions, heptad repeats 1 and 2 (HR1 and HR2), which rearrange to form a six-helix bundle to enable membrane fusion. The E and M proteins are present in the viral membranes and are required for viral assembly, budding, and intracellular trafficking.<fig id="fig1"><label>Figure 1</label><caption><p>MERS-CoV structure, genome organisation, and replication</p><p>MERS-CoV encodes a large replicase-transcriptase polyprotein (rep1A and rep1B), which is processed into 16 non-structural proteins (nsp). These proteins are required for the formation of the replicase-transcription complex, for cleavage of the polyprotein, and for immune evasion. Structural proteins (spike [S], envelope [E], membrane [M], and nucleocapsid [N]) and accessory proteins (ORFs 3, 4a, 4b, 5, 8b) are encoded in the end third of the 3' end of the genome of the genome. MERS-CoV binds to its cellular receptor DPP4 via the S protein, which is processed by host proteases to expose a fusion peptide. The viral genome is then released into the cytoplasm, where it is translated on host ribosomes into rep1A and rep1B proteins. The polyprotein is cleaved by two viral-encoded proteases, encoded by nsp3 and nsp5. Proteins involved in genome and subgenome replication and transcription include nsp12 (the RNA-dependent RNA polymerase [RdRP]) and two associated proteins, nsp7 and nsp8.<xref rid="bib127" ref-type="bibr"><sup>127</sup></xref> Nsp13 (a helicase), nsp14 (which encodes an N7 methyltransferase and ExoN, a protein required for genome fidelity), and nsp16 (a 2'-O methyltransferase) are also necessary for optimal genomic and subgenomic RNA synthesis. MERS-CoV transcription involves the synthesis of subgenomic RNAs, which encode the structural and accessory proteins located at the 3' end of the genome. Subgenomic and genomic RNAs are co-terminal, sharing the same 5' leader and 3' sequences. Subgenomic RNAs code for structural and accessory proteins (ORF3, 4a, 4b, 5, and 8b). ORF8b is encoded within the N gene (marked with purple lines). These accessory proteins are believed to have immunoevasive properties, but are not essential for replication, and are variably deleted in human and camel virus isolates.<xref rid="bib128" ref-type="bibr">128</xref>, <xref rid="bib129" ref-type="bibr">129</xref>, <xref rid="bib130" ref-type="bibr">130</xref> Genomic replication occurs on membrane structures such as double membrane vesicles (DMVs), convoluted membranes (CM), and vesicle packets (VP), which are merged DMV<xref rid="bib131" ref-type="bibr"><sup>131</sup></xref> that have been formed from the rough endoplasmic reticulum (RER) by the combined action of nsp3, nsp4, and nsp6 (lower right). After synthesis on replicase-transcription complexes, RNA is encapsidated by the N protein and transported to the ERGIC (endoplasmic reticulum–Golgi compartment), where budding into membranes containing the S, E, and M proteins occurs before release from the cell. 3CLPro=chymotrypsin-like protease. ExoN=exonuclease. MERS-CoV=Middle East respiratory syndrome coronavirus. MTase=methyltransferase. NendoU=nidoviral uridylate-specific endoribonuclease. NF-κB=nuclear factor κ-light-chain-enhancer of activated B cells. NTPase=nucleoside-triphosphatase. pp1a=polyprotein 1a. PLPro=papain-like protease.</p></caption><graphic xlink:href="gr1_lrg"></graphic></fig></p><p id="para1430">MERS-CoV enters host cells via binding of its S protein to the host cell DPP4 receptor (<xref rid="fig1" ref-type="fig">figure 1</xref>; <xref rid="sec1" ref-type="sec">appendix pp 2–3</xref>).<xref rid="bib15" ref-type="bibr">15</xref>, <xref rid="bib17" ref-type="bibr">17</xref> DPP4 is less abundant in the nasal cavity and epithelial cells of the upper airways but is highly expressed on the epithelial cells of the distal airways and type I and II pneumocytes in the lung alveoli, non-ciliated bronchial epithelial cells, endothelial cells, and some haemopoietic cells.<xref rid="bib15" ref-type="bibr"><sup>15</sup></xref> DPP4 is also widely expressed on the epithelial cells of several other organs and tissues such as the kidneys, intestine, liver, thymus, and bone marrow—thus widespread dissemination of MERS-CoV could occur in the body. The structures of the S protein of MERS-CoV and other coronaviruses have been determined using cryo-electron microscopy<xref rid="bib16" ref-type="bibr">16</xref>, <xref rid="bib17" ref-type="bibr">17</xref> and provide the basis for rational design of protective antibodies and other therapeutics.</p></sec><sec id="cesec30"><title>Epidemiology</title><p id="para1440">A primary MERS-CoV infection is defined by WHO as a laboratory-confirmed MERS-CoV infection that has no direct epidemiological link to a human MERS-CoV infection, and was acquired outside of a health-care facility presumably from direct or indirect contact with the reservoir host—dromedary camels.<xref rid="bib19" ref-type="bibr"><sup>19</sup></xref></p><p id="para1450">A secondary MERS-CoV infection is defined by WHO as a laboratory-confirmed MERS-CoV infection with a direct epidemiological link to an individual with confirmed or probable MERS-CoV infection.<xref rid="bib19" ref-type="bibr"><sup>19</sup></xref></p><sec id="cesec40"><title>Geographical distribution</title><p id="para1460">Laboratory-confirmed MERS-CoV human infections<xref rid="bib19" ref-type="bibr"><sup>19</sup></xref> are reported to WHO as a requirement under the International Health Regulations (2005). The geographical distribution of countries reporting laboratory-confirmed human MERS cases and the numbers reported over time are shown in <xref rid="fig2" ref-type="fig">Figure 2</xref>, <xref rid="fig3" ref-type="fig">Figure 3</xref>. Between April, 2012 and end of December, 2019, 2499 laboratory-confirmed human cases of MERS-CoV infection, including 858 deaths (34·3% mortality) were reported from 27 countries in all continents (<xref rid="fig2" ref-type="fig">figure 2</xref>) to WHO, the majority of which were reported by Saudi Arabia (2106 cases, 780 deaths).<fig id="fig2"><label>Figure 2</label><caption><p>Geographical distribution of reported human infections of MERS-CoV</p><p>Cases reported up to and including Dec 31, 2019. MERS-CoV=Middle East respiratory syndrome coronavirus. Reproduced from Dr Mamunur R Malik, WHO Regional Office for the Eastern Mediterranean.</p></caption><graphic xlink:href="gr2_lrg"></graphic></fig><fig id="fig3"><label>Figure 3</label><caption><p>Global MERS reported to WHO by week, 2012–19</p><p>Reproduced from WHO website, by permission of Dr Mamunur R Malik, WHO Regional Office for the Eastern Mediterranean. MERS=Middle East respiratory syndrome.</p></caption><graphic xlink:href="gr3_lrg"></graphic></fig></p></sec><sec id="cesec50"><title>Sources of infection</title><p id="para1470">The origin of all primary human MERS-CoV infections remains unknown. Dromedary camels are a host reservoir species for the MERS-CoV (<xref rid="sec1" ref-type="sec">appendix pp 3–5</xref>).<xref rid="bib20" ref-type="bibr">20</xref>, <xref rid="bib21" ref-type="bibr">21</xref>, <xref rid="bib22" ref-type="bibr">22</xref>, <xref rid="bib23" ref-type="bibr">23</xref> Humans can acquire MERS-CoV through direct or indirect contact with infected dromedary camels or infected patients<xref rid="bib19" ref-type="bibr">19</xref>, <xref rid="bib20" ref-type="bibr">20</xref>, <xref rid="bib21" ref-type="bibr">21</xref>, <xref rid="bib22" ref-type="bibr">22</xref>, <xref rid="bib23" ref-type="bibr">23</xref>, <xref rid="bib24" ref-type="bibr">24</xref>, <xref rid="bib25" ref-type="bibr">25</xref>, <xref rid="bib26" ref-type="bibr">26</xref>, <xref rid="bib27" ref-type="bibr">27</xref>, <xref rid="bib28" ref-type="bibr">28</xref>, <xref rid="bib29" ref-type="bibr">29</xref>, <xref rid="bib30" ref-type="bibr">30</xref> (<xref rid="fig4" ref-type="fig">figure 4A</xref>). However not all cases infected in the community report contact with dromedary camels (<xref rid="sec1" ref-type="sec">appendix p 4–5</xref>). The transmission of MERS-CoV from dromedary camels to humans is now well documented in the Arabian Peninsula,<xref rid="bib23" ref-type="bibr">23</xref>, <xref rid="bib24" ref-type="bibr">24</xref>, <xref rid="bib25" ref-type="bibr">25</xref> but the extent to which this transmission is occurring in countries outside the Arabian Peninsula requires definition. Experimental infections have shown that infected dromedaries shed MERS-CoV from their nasal secretions with minimal signs of illness, which is limited to rhinorrhoea.<xref rid="bib27" ref-type="bibr">27</xref>, <xref rid="bib28" ref-type="bibr">28</xref>, <xref rid="bib29" ref-type="bibr">29</xref> Full-genome phylogenetic analysis indicates that evolution of diverse MERS-CoV lineages in camels have caused human infections, perpetuating a low barrier for interspecies transmission.<xref rid="bib21" ref-type="bibr">21</xref>, <xref rid="bib29" ref-type="bibr">29</xref>, <xref rid="bib30" ref-type="bibr">30</xref> However, African MERS-CoV lineages in camels imported into Saudi Arabia have not established themselves in camels in Saudi Arabia,<xref rid="bib9" ref-type="bibr">9</xref>, <xref rid="bib30" ref-type="bibr">30</xref> indicating potential differences in transmission dynamics and selection pressure. Analysis of population dynamics shows that Arabian viruses can maintain endemicity without introduction of additional lineages.<xref rid="bib9" ref-type="bibr">9</xref>, <xref rid="bib30" ref-type="bibr">30</xref> WHO is supporting molecular and serological studies at the dromedary–human interface in several countries in Africa and south Asia.<xref rid="bib31" ref-type="bibr"><sup>31</sup></xref> The phylogenetic relationship of complete genomes of MERS-CoV strains obtained from camels and humans has been published.<xref rid="bib32" ref-type="bibr"><sup>32</sup></xref><fig id="fig4"><label>Figure 4</label><caption><p>Epidemiological, clinical, and laboratory features of MERS</p><p>ALT=alanine aminotransferase. AST=asparate aminotransferase. MERS-CoV=Middle East respiratory syndrome coronavirus.</p></caption><graphic xlink:href="gr4_lrg"></graphic></fig></p></sec><sec id="cesec60"><title>Epidemiological patterns of human cases</title><p id="para1480">The epidemiological patterns of MERS-CoV in humans have remained consistent since MERS-CoV was first identified in 2012.<xref rid="bib2" ref-type="bibr"><sup>2</sup></xref> Primary cases often report direct or indirect contact with dromedary camels and present across a wide clinical spectrum from mild to severe fulminant disease. Individuals with severe primary MERS-CoV infections are often older than 65 years with comorbidities, and symptoms can present late. Individuals with mild primary MERS-CoV infections are often missed by current surveillance systems since they usually do not present to health-care facilities.</p><p id="para1490">Secondary cases have resulted from human-to-human transmission among close contacts. To date, secondary transmission has occasionally occurred between close contacts of individuals with laboratory-confirmed MERS-CoV in household settings.<xref rid="bib33" ref-type="bibr">33</xref>, <xref rid="bib34" ref-type="bibr">34</xref> However, secondary transmission in health-care facilities has repeatedly occurred in several countries and has, on occasion, resulted in large outbreaks (<xref rid="sec1" ref-type="sec">appendix p 5</xref>)—such as Jeddah, Saudi Arabia (2014), Seoul, South Korea (2015), and Riyadh, Saudi Arabia (2015, 2016, and 2018). In health-care settings, human-to-human transmission occurs between patients, between patients and health-care workers, and from patients to visitors.<xref rid="bib21" ref-type="bibr">21</xref>, <xref rid="bib33" ref-type="bibr">33</xref> Approximately half of the MERS-CoV cases reported to WHO<xref rid="bib2" ref-type="bibr"><sup>2</sup></xref> to date have resulted from human-to-human transmission in health-care facilities.<xref rid="bib21" ref-type="bibr">21</xref>, <xref rid="bib33" ref-type="bibr">33</xref></p></sec><sec id="cesec70"><title>Risk factors and transmission</title><p id="para1500">Known risk factors for MERS-CoV acquisition, transmission, and outbreaks are noted (<xref rid="box1" ref-type="boxed-text">panel 1</xref>). MERS patient data reported to WHO includes information on exposures and known risk factors during the 14 days before symptom onset, or during the 14 days before laboratory confirmation was reported (in the case of asymptomatic infection). Exposure data include travel history to MERS-CoV endemic countries, direct or indirect contact with dromedary camels or their products, contact with humans with MERS-CoV infection, and visits to health-care facilities containing patients infected with MERS-CoV are risk factors for acquiring MERS-CoV infection (<xref rid="sec1" ref-type="sec">appendix pp 4–5</xref>).<xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib24" ref-type="bibr">24</xref>, <xref rid="bib25" ref-type="bibr">25</xref>, <xref rid="bib31" ref-type="bibr">31</xref>, <xref rid="bib32" ref-type="bibr">32</xref>, <xref rid="bib33" ref-type="bibr">33</xref>, <xref rid="bib34" ref-type="bibr">34</xref>, <xref rid="bib35" ref-type="bibr">35</xref>, <xref rid="bib36" ref-type="bibr">36</xref>, <xref rid="bib37" ref-type="bibr">37</xref>, <xref rid="bib38" ref-type="bibr">38</xref>, <xref rid="bib39" ref-type="bibr">39</xref>, <xref rid="bib40" ref-type="bibr">40</xref>, <xref rid="bib41" ref-type="bibr">41</xref>, <xref rid="bib42" ref-type="bibr">42</xref>, <xref rid="bib43" ref-type="bibr">43</xref>, <xref rid="bib44" ref-type="bibr">44</xref>, <xref rid="bib45" ref-type="bibr">45</xref> MERS-CoV has been detected in camel products (eg, raw milk, meat, blood, urine, or birth products); however, genomic studies to definitively show transmission from these products to humans have not yet been done. Human primary intestinal epithelial cells, small intestine explants, and the intestinal tract are highly susceptible to MERS-CoV and can sustain viral replication. After infection of mice transgenic for the expression of the host DPP4 receptor, histological examination showed MERS-CoV enteric infection in all inoculated mice with progression to infection of the lung tissues, indicating the development of sequential respiratory infection.<xref rid="bib39" ref-type="bibr"><sup>39</sup></xref><boxed-text id="box1"><label>Panel 1</label><caption><title>Risk factors for MERS-CoV infection, transmission, and outbreaks21,34,38,132–138</title></caption><p id="para10"><bold>Community risk factors</bold></p><p id="para20"><list list-type="simple" id="celist10"><list-item id="celistitem10"><label>•</label><p id="para30">Indirect or direct contact with MERS-CoV-infected camels, camel nasal secretions, milk, urine, faeces, meat, or birthing products</p></list-item><list-item id="celistitem20"><label>•</label><p id="para40">Travel to the Middle East and contact with camels or attendance at a health facility</p></list-item><list-item id="celistitem30"><label>•</label><p id="para50">Exposure to, or contact with, patients with MERS-CoV in the community, or at healthcare facilities</p></list-item><list-item id="celistitem40"><label>•</label><p id="para60">Underlying chronic medical conditions</p></list-item></list></p><p id="para70"><bold>Nosocomial risk factors for human-to-human transmission and outbreak amplification</bold></p><p id="para80"><list list-type="simple" id="celist20"><list-item id="celistitem50"><label>•</label><p id="para90">Late diagnosis of MERS-CoV infection</p></list-item><list-item id="celistitem60"><label>•</label><p id="para100">Lack of awareness in health-care workers of the possibility of MERS in patients with a fever</p></list-item><list-item id="celistitem70"><label>•</label><p id="para110">Overcrowded or contaminated health-care facilities, especially emergency departments, dialysis units, and crowded inpatient wards</p></list-item><list-item id="celistitem80"><label>•</label><p id="para120">Exposure of hospital staff or other patients to symptomatic patients with MERS</p></list-item><list-item id="celistitem90"><label>•</label><p id="para130">Delayed implementation of infection control measures</p></list-item><list-item id="celistitem100"><label>•</label><p id="para140">Poor compliance with MERS-specific infection control guidelines (hand hygiene, droplet and contact precautions, environmental cleaning)</p></list-item><list-item id="celistitem110"><label>•</label><p id="para150">Poor compliance with appropriate personal protective equipment when assessing patients with febrile respiratory illness</p></list-item><list-item id="celistitem120"><label>•</label><p id="para160">Aerosol-generating procedures or invasive procedures in patients with MERS (eg, nebulisers, resuscitation, intubation, and ventilation)</p></list-item><list-item id="celistitem130"><label>•</label><p id="para170">Lack of proper isolation room facilities</p></list-item><list-item id="celistitem140"><label>•</label><p id="para180">Distance between patient beds of less than 1 m</p></list-item><list-item id="celistitem150"><label>•</label><p id="para190">Friends and family members staying as caregivers in overcrowded health-care facilities</p></list-item></list></p><p id="para200">MERS=Middle East respiratory syndrome. MERS-CoV=Middle East respiratory syndrome coronavirus.</p></boxed-text></p><p id="para1510">Transmission via contact with contaminated hospital environments is possible during outbreaks, although genomic studies providing an evidence base are lacking. Since environmental contamination is a potential source of infection, it is prudent to take precautionary infection control measures.</p></sec><sec id="cesec80"><title>Nosocomial transmission</title><p id="para1520">Health-care-associated outbreaks of MERS-CoV affecting inpatients, health-care workers, and visitors are characteristic of MERS (<xref rid="box2" ref-type="boxed-text">panel 2</xref>) and account for approximately 50% of reported cases.<xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib20" ref-type="bibr">20</xref>, <xref rid="bib21" ref-type="bibr">21</xref>, <xref rid="bib33" ref-type="bibr">33</xref>, <xref rid="bib40" ref-type="bibr">40</xref>, <xref rid="bib41" ref-type="bibr">41</xref>, <xref rid="bib42" ref-type="bibr">42</xref>, <xref rid="bib43" ref-type="bibr">43</xref>, <xref rid="bib44" ref-type="bibr">44</xref>, <xref rid="bib45" ref-type="bibr">45</xref> Large nosocomial outbreaks have occurred in Abu Dhabi in United Arab Emirates, Seoul in South Korea and several cities in Saudi Arabia (<xref rid="sec1" ref-type="sec">appendix p 5</xref>). The 2013 outbreak in Al Hasa, Saudi Arabia, involved 23 people in three different hospitals and was linked to poor infection control practices, aerosol-generating procedures, continuous positive pressure ventilation, and cardiopulmonary resuscitation.<xref rid="bib42" ref-type="bibr"><sup>42</sup></xref> In June, 2017, an outbreak of 34 MERS-CoV cases (including 17 in health-care workers) occurred in a hospital in Riyadh, Saudi Arabia,<xref rid="bib43" ref-type="bibr"><sup>43</sup></xref> where the primary case was a 47-year-old man admitted for emergency intubation. Before a diagnosis of MERS, this individual had contact with 220 health-care workers, patients, and visitors. Another 2017 outbreak in Riyadh involved three hospitals, with 44 MERS cases in patients, health-care workers, and family members. The outbreak arose from three severely ill people who were diagnosed with MERS late in the disease course, and involved in a superspreading event.<xref rid="bib44" ref-type="bibr"><sup>44</sup></xref> In 2015, South Korea had the largest MERS-CoV outbreak outside the Middle East with 186 cases reported, resulting from a single imported case from an individual who had returned from travelling in the Middle East. The outbreak included 185 secondary cases who acquired infection in 16 health-care facilities and 80% of transmission events were attributed to five superspreading events.<xref rid="bib45" ref-type="bibr"><sup>45</sup></xref><boxed-text id="box2"><label>Panel 2</label><caption><title>MERS prevention and interventions21,31,33,36,67</title></caption><p id="para210"><bold>The pathogen: MERS-CoV</bold></p><p id="para220"><list list-type="simple" id="celist30"><list-item id="celistitem160"><label>•</label><p id="para230">Anti-viral therapeutics including host-directed therapies or immune-based therapies are in development.</p></list-item></list></p><p id="para240"><bold>Intermediate host reservoir: dromedary camels</bold></p><p id="para250"><list list-type="simple" id="celist40"><list-item id="celistitem170"><label>•</label><p id="para260">Vaccinating dromedary camels, the source for primary human infection, is a proposed approach to preventing human infection.</p></list-item><list-item id="celistitem180"><label>•</label><p id="para270">A recombinant camelpox virus expressing the S protein has been shown to induce neutralising antibodies in camels.</p></list-item><list-item id="celistitem190"><label>•</label><p id="para280">As compared to older camels, juvenile camels have higher rates of viral shedding. Past infection is not protective.</p></list-item></list></p><p id="para290"><bold>Humans with contact with infected camels</bold></p><p id="para300"><list list-type="simple" id="celist50"><list-item id="celistitem200"><label>•</label><p id="para310">Basic hand hygiene practices.</p></list-item><list-item id="celistitem210"><label>•</label><p id="para320">Gloves and face masks when handling infected camels and camel products.</p></list-item><list-item id="celistitem220"><label>•</label><p id="para330">Pasteurising camel milk.</p></list-item><list-item id="celistitem230"><label>•</label><p id="para340">Avoid ingesting raw camel meat, dairy products, or urine.</p></list-item><list-item id="celistitem240"><label>•</label><p id="para350">Vaccine development for people with high camel exposure.</p></list-item></list></p><p id="para360"><bold>Human cases</bold></p><p id="para370"><list list-type="simple" id="celist60"><list-item id="celistitem250"><label>•</label><p id="para380">High clinical awareness of the possibility of MERS-CoV infection and making early diagnosis.</p></list-item><list-item id="celistitem260"><label>•</label><p id="para390">Isolate suspected cases early and institute infection control measures.</p></list-item><list-item id="celistitem270"><label>•</label><p id="para400">Face masks and hand hygiene measures for all HCW and family contacts.</p></list-item><list-item id="celistitem280"><label>•</label><p id="para410">Occupationally exposed people have a higher risk of infection compared to the general public. Human surveillance is focused on diseased people, and those with subclinical or asymptomatic infection and could serve as a source of infection of a susceptible person with comorbidities.</p></list-item></list></p><p id="para420"><bold>Nosocomial and community outbreaks</bold></p><p id="para430"><list list-type="simple" id="celist70"><list-item id="celistitem290"><label>•</label><p id="para440">Nosocomial cases and outbreaks are diminishing due to institution of stringent infection control measures but still account for 35–50% of cases.</p></list-item><list-item id="celistitem300"><label>•</label><p id="para450">More than 20 human vaccines have been developed and are being tested in animals—some are in human phase 1 or 2 trials.</p></list-item></list></p><p id="para460">MERS=Middle East respiratory syndrome. MERs-CoV=Middle East respiratory syndrome coronavirus.</p></boxed-text></p></sec></sec><sec id="cesec90"><title>Pathogenesis and pathology</title><p id="para1530">The mechanisms underlying the pathogenesis of MERS-CoV remain to be defined because autopsies are generally not done either for religious and cultural reasons or to prevent environmental contamination with subsequent infection of health-care workers. Therefore, there are few data on the histopathological changes in patients with MERS-CoV infection, even in severe disease.<xref rid="bib46" ref-type="bibr">46</xref>, <xref rid="bib47" ref-type="bibr">47</xref> The only two autopsies available show that viral infection was confined predominantly to the respiratory tract, although viral particles were detected in the kidney in one of the reports.<xref rid="bib47" ref-type="bibr"><sup>47</sup></xref> Further, ex vivo human kidney cultures were shown to support productive MERS-CoV infection.<xref rid="bib48" ref-type="bibr"><sup>48</sup></xref> However, it is not known whether infection of this organ contributes to worse outcomes compared with infections confined to the respiratory tract. Viral RNA, but not infectious MERS-CoV, was detected in the blood for at least 2 weeks after diagnosis. Whether this viral RNA represented an extrapulmonary infection is not clear, since MERS-CoV neutralising antibody was detected in the serum at the same time in some patients.<xref rid="bib49" ref-type="bibr"><sup>49</sup></xref></p><p id="para1540">Pathological changes in the lungs include evidence of focal haemorrhagic necrotising pneumonia with exudative diffuse alveolar damage, indistinguishable from findings detected in severe pneumonia caused by other viral agents.</p><p id="para1550">Several experimentally infected animal models for MERS have been developed (<xref rid="sec1" ref-type="sec">appendix p 6</xref>).<xref rid="bib50" ref-type="bibr">50</xref>, <xref rid="bib51" ref-type="bibr">51</xref> Methods for gene silencing and editing are being further developed, therefore it is likely that additional viral and host factors important in MERS-CoV pathogenesis will be identified.</p></sec><sec id="cesec100"><title>Protective and deleterious immune responses</title><p id="para1560">MERS-CoV pathogenesis reflects a balance between coronavirus-induced protective and pathogenic host immune responses and direct cytotoxic effects of the virus.<xref rid="bib52" ref-type="bibr"><sup>52</sup></xref> According to studies of patients infected with SARS-CoV and of mice and other animals infected experimentally with MERS-CoV, successful resolution of MERS and long-term protection from re-infection likely requires well coordinated innate and adaptive B-cell and T-cell responses. In patients with SARS, innate immune responses characterised by an extended period of cytokine secretion (eg, IFNα and IFNβ) was correlated with delayed antibody responses and poor management outcomes; this prolonged innate response has not yet been shown in patients infected with MERS-CoV.<xref rid="bib53" ref-type="bibr"><sup>53</sup></xref> MERS-CoV productively infects activated human T cells and induces delayed cytokine responses after infection of human myeloid cells in vitro, both of which could impair virus clearance and the development of an effective immune response.<xref rid="bib54" ref-type="bibr">54</xref>, <xref rid="bib55" ref-type="bibr">55</xref>, <xref rid="bib56" ref-type="bibr">56</xref></p><p id="para1570">During the acute phase of MERS, robust virus-specific CD8 T-cell responses were detected in most patients with severe or moderate disease, with antibody and CD4 T-cell responses appearing later in the disease course.<xref rid="bib57" ref-type="bibr"><sup>57</sup></xref> T-cell and antibody responses were reliably detected 2–3 weeks after diagnosis, although they were detected earlier in some patients.<xref rid="bib49" ref-type="bibr">49</xref>, <xref rid="bib57" ref-type="bibr">57</xref> Studies of MERS survivors showed that MERS-CoV-specific antibody responses tended to be lower and transient in patients with mild or subclinical disease when compared with patients with severe disease, in whom MERS-CoV-specific antibody responses were detected for at least 2 years.<xref rid="bib57" ref-type="bibr">57</xref>, <xref rid="bib58" ref-type="bibr">58</xref>, <xref rid="bib59" ref-type="bibr">59</xref>, <xref rid="bib60" ref-type="bibr">60</xref> In contrast, T-cell responses were detected in all MERS survivors for at least 2 years.<xref rid="bib59" ref-type="bibr"><sup>59</sup></xref></p><p id="para1580">The transitory nature of the antibody response in mild disease and greater stability of the T-cell response suggest that induction of both will be required for optimal long-term protection; the measurement of both will enhance the accuracy of prevalence studies.</p></sec><sec id="cesec110"><title>Clinical features</title><sec id="cesec120"><title>Incubation period</title><p id="para1590">The specific exposures that lead to sporadic MERS-CoV infections are unknown, therefore it is impossible to estimate the incubation period in primary cases. However, based on data from cases of human-to-human transmission, the incubation period is a median of 5–7 days, with a range of 2–14 days (median 5·2 days [95% CI 1·9–14·7]).<xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib10" ref-type="bibr">10</xref>, <xref rid="bib21" ref-type="bibr">21</xref>, <xref rid="bib61" ref-type="bibr">61</xref>, <xref rid="bib62" ref-type="bibr">62</xref>, <xref rid="bib63" ref-type="bibr">63</xref> Immunocompromised patients can present with longer incubation periods of up to 20 days.<xref rid="bib64" ref-type="bibr"><sup>64</sup></xref></p></sec><sec id="cesec130"><title>Presentation in adults</title><p id="para1600">The clinical presentation of patients infected with MERS-CoV ranges from asymptomatic or mild upper respiratory illness to rapidly progressive pneumonitis, respiratory failure, acute respiratory distress syndrome, septic shock, and multiorgan failure with fatal outcome (<xref rid="fig5" ref-type="fig">figure 5</xref>).<xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib10" ref-type="bibr">10</xref>, <xref rid="bib11" ref-type="bibr">11</xref>, <xref rid="bib61" ref-type="bibr">61</xref>, <xref rid="bib62" ref-type="bibr">62</xref>, <xref rid="bib63" ref-type="bibr">63</xref>, <xref rid="bib64" ref-type="bibr">64</xref>, <xref rid="bib65" ref-type="bibr">65</xref>, <xref rid="bib66" ref-type="bibr">66</xref>, <xref rid="bib67" ref-type="bibr">67</xref>, <xref rid="bib68" ref-type="bibr">68</xref>, <xref rid="bib69" ref-type="bibr">69</xref>, <xref rid="bib70" ref-type="bibr">70</xref> It is not possible to distinguish patients with a legitimate asymptomatic MERS-CoV infection from those who develop mild disease because reports to WHO provide signs and symptoms information only at the time of reporting. Many individuals remain asymptomatic whereas some go on to develop mild disease, which is why WHO classifies these individuals as mild or asymptomatic. Asymptomatic-to-mild infection rates of 25–50% have been reported.<fig id="fig5"><label>Figure 5</label><caption><p>Chest imaging abnormalities in patients with Middle East respiratory syndrome</p><p>(A) Chest x-rays showing bilateral extensive diffuse and focal opacities. (B) Chest CT scan showing bilateral extensive ground-glass reticulonodular shadowing with bronchiolar wall thickening.</p></caption><graphic xlink:href="gr5_lrg"></graphic></fig></p><p id="para1610">The signs and symptoms associated with MERS are non-specific, with or without multisystem involvement, and thus could be mistaken for other causes of respiratory tract or gastrointestinal illnesses.<xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib10" ref-type="bibr">10</xref>, <xref rid="bib11" ref-type="bibr">11</xref>, <xref rid="bib61" ref-type="bibr">61</xref>, <xref rid="bib62" ref-type="bibr">62</xref>, <xref rid="bib63" ref-type="bibr">63</xref>, <xref rid="bib64" ref-type="bibr">64</xref>, <xref rid="bib65" ref-type="bibr">65</xref>, <xref rid="bib66" ref-type="bibr">66</xref>, <xref rid="bib67" ref-type="bibr">67</xref>, <xref rid="bib68" ref-type="bibr">68</xref>, <xref rid="bib69" ref-type="bibr">69</xref>, <xref rid="bib70" ref-type="bibr">70</xref> Therefore, the clinical diagnosis of MERS can be easily missed. Patients with MERS can typically present with fever, chills, rigors, headache, a non-productive cough, sore throat, arthralgia, and myalgia followed by dyspnoea. Other associated symptoms include coryza, nausea, vomiting, dizziness, sputum production, diarrhoea, and abdominal pain. Some patients with MERS can present with atypical symptoms of mild respiratory illness without a fever and a gastrointestinal illness that precedes the development of pneumonia.<xref rid="bib64" ref-type="bibr">64</xref>, <xref rid="bib67" ref-type="bibr">67</xref>, <xref rid="bib68" ref-type="bibr">68</xref> Neuromuscular manifestations include hypersomnolence, weakness, and tingling in the extremities similar to Guillain-Barré syndrome or virus-related sensory neuropathy.<xref rid="bib68" ref-type="bibr"><sup>68</sup></xref> Co-infection of MERS-CoV with other respiratory viruses (such as parainfluenza virus, rhinovirus, influenza A or B virus, respiratory syncytial virus, enteroviruses, and human metapneumovirus) and nosocomial bacterial infections has been reported in patients receiving intensive care.<xref rid="bib61" ref-type="bibr">61</xref>, <xref rid="bib67" ref-type="bibr">67</xref></p></sec><sec id="cesec140"><title>Immunocompromised patients or those with comorbidities</title><p id="para1620">Immunocompromised patients or patients with chronic heart, liver, and kidney disease can present with atypical features, such as a longer incubation period, a longer period from initial PCR positivity to symptom onset, persistent prolonged viral shedding, and increased mortality.<xref rid="bib64" ref-type="bibr">64</xref>, <xref rid="bib65" ref-type="bibr">65</xref>, <xref rid="bib66" ref-type="bibr">66</xref>, <xref rid="bib67" ref-type="bibr">67</xref>, <xref rid="bib68" ref-type="bibr">68</xref>, <xref rid="bib69" ref-type="bibr">69</xref>, <xref rid="bib70" ref-type="bibr">70</xref> MERS-CoV causes more severe disease in people older than 60 years, and those with chronic comorbid diseases such as renal disease, cancer, chronic lung disease, immunosuppression, and diabetes.</p></sec><sec id="cesec150"><title>Children, pregnant women, and returning travelers</title><p id="para1630">In children yonger than 5 years, MERS-CoV infection appears to be rare, and usually presents as mild disease with cough as the predominant clinical symptom. Acute and severe respiratory illness (ie, a fatal outcome after multiorgan failure) has been noted in only two of 38 reported paediatric cases and these were in boys aged 9 months and 2 years with comorbidities (infantile nephrotic syndrome and cystic fibrosis, respectively).<xref rid="bib71" ref-type="bibr">71</xref>, <xref rid="bib72" ref-type="bibr">72</xref>, <xref rid="bib73" ref-type="bibr">73</xref>, <xref rid="bib74" ref-type="bibr">74</xref> Data on the prevalence of MERS-CoV in pregnant women are limited to case reports, and the clinical presentations and mortality rates are similar to non-pregnant women.<xref rid="bib75" ref-type="bibr"><sup>75</sup></xref></p><p id="para1640">MERS should be kept on the differential diagnosis list for ill travellers returning home from MERS-CoV endemic areas who present with acute febrile illness (temperature ≥38°C), aches and pains, headache, cough, dyspnoea, diarrhoea, nausea, vomiting, unexplained leucopenia (white blood cell count <3·5 × 110<sup>9</sup>/L), and thrombocytopenia (platelets <150 × 10<sup>9</sup>/L)—either with or without prominent respiratory symptoms.<xref rid="bib2" ref-type="bibr">2</xref>, <xref rid="bib10" ref-type="bibr">10</xref>, <xref rid="bib11" ref-type="bibr">11</xref>, <xref rid="bib61" ref-type="bibr">61</xref>, <xref rid="bib62" ref-type="bibr">62</xref>, <xref rid="bib63" ref-type="bibr">63</xref>, <xref rid="bib64" ref-type="bibr">64</xref>, <xref rid="bib65" ref-type="bibr">65</xref>, <xref rid="bib66" ref-type="bibr">66</xref>, <xref rid="bib67" ref-type="bibr">67</xref>, <xref rid="bib68" ref-type="bibr">68</xref>, <xref rid="bib69" ref-type="bibr">69</xref>, <xref rid="bib70" ref-type="bibr">70</xref> It is important that clinicians are alert to the possibility that patients could have MERS in all health-care settings where the virus is circulating so that an accurate diagnosis can be made and infection control measures implemented efficiently.<xref rid="bib76" ref-type="bibr"><sup>76</sup></xref></p></sec></sec><sec id="cesec160"><title>Clinical specimen types for diagnosis</title><p id="para1650">The type and quality of the clinical specimen are important in the laboratory diagnosis of MERS-CoV infection. Both upper respiratory tract specimens (oropharyngeal or nasopharyngeal swabs) and lower respiratory tract specimens (sputum, endotracheal aspirate or lavage) should be analysed whenever possible.<xref rid="bib77" ref-type="bibr">77</xref>, <xref rid="bib78" ref-type="bibr">78</xref>, <xref rid="bib79" ref-type="bibr">79</xref> Patients with MERS might not shed the virus during the early stage of their illness; thus, initial negative results from upper respiratory samples do not rule out the possibility of MERS and patients should be retested using a lower respiratory tract sample. Several studies of MERS-CoV viral load measurements show that upper respiratory tract specimens have lower viral loads than lower respiratory specimens.<xref rid="bib11" ref-type="bibr">11</xref>, <xref rid="bib12" ref-type="bibr">12</xref>, <xref rid="bib79" ref-type="bibr">79</xref>, <xref rid="bib80" ref-type="bibr">80</xref> MERS-CoV RNA has been detected in blood, urine, and stool—but at much lower viral loads than in the respiratory tract.<xref rid="bib81" ref-type="bibr">81</xref>, <xref rid="bib82" ref-type="bibr">82</xref></p><p id="para1660">Clinical specimens must be collected by trained staff using appropriate personal protective equipment—eg, when taking nasopharyngeal and oropharyngeal specimens, Dacron or rayon swabs specifically designed for collecting specimens for virology must be used.<xref rid="bib77" ref-type="bibr">77</xref>, <xref rid="bib78" ref-type="bibr">78</xref>, <xref rid="bib83" ref-type="bibr">83</xref> These swab kits should contain virus transport medium. A single negative test result does not exclude the diagnosis and repeat sampling and testing is strongly recommended.<xref rid="bib83" ref-type="bibr"><sup>83</sup></xref> A minimum of two samples, preferably from the lower respiratory tract, are needed to exclude MERS-CoV after initial assessment. To confirm clearance of the virus, respiratory samples should be collected sequentially (every 2 to 4 days) over ensuing days until there are two consecutive negative results at least 24 h apart in people who are clinically recovered.<xref rid="bib77" ref-type="bibr"><sup>77</sup></xref></p></sec><sec id="cesec170"><title>Laboratory testing</title><p id="para1670">WHO guidelines for testing should be followed.<xref rid="bib77" ref-type="bibr"><sup>77</sup></xref> MERS-CoV testing must be performed in appropriately equipped biosafety laboratories by staff trained in the relevant technical and safety procedures. National or WHO guidelines on the laboratory biosafety should be followed in all circumstances.<xref rid="bib83" ref-type="bibr"><sup>83</sup></xref></p><p id="para1680">Three real-time RT-PCR (rRT-PCR) assays for routine detection of MERS-CoV have been developed targeting upstream of the E protein gene (upE) and open reading frame (ORF)1b and ORF1a. The assay for the upE target is considered highly sensitive and is recommended for screening, with the ORF1a assay (ORF1a assay is considered more sensitive than ORF1b assay).<xref rid="bib77" ref-type="bibr"><sup>77</sup></xref></p><p id="para1690">An updated roadmap for MERS-CoV product development lists all available diagnostics and other diagnostics in the developmental phase.<xref rid="bib84" ref-type="bibr"><sup>84</sup></xref> Several diagnostic tests are under development to accelerate turnaround times from sample analysis to result.<xref rid="bib85" ref-type="bibr">85</xref>, <xref rid="bib86" ref-type="bibr">86</xref>, <xref rid="bib87" ref-type="bibr">87</xref> A 2018 rapid and specific assay for the detection of MERS-CoV combines the reverse transcription loop-mediated isothermal amplification technique and a vertical flow visualisation strip (RT-LAMP-VF) to detect the nucleocapsid gene of MERS-CoV.<xref rid="bib86" ref-type="bibr"><sup>86</sup></xref> The RT-LAMP-VF assay provides detection of MERS-CoV within 35 min and is easier to perform than the WHO-recommended rRT-PCR method.<xref rid="bib86" ref-type="bibr"><sup>86</sup></xref></p><p id="para1700">Several serological assays are available for detection of MERS-CoV: ELISA, recombinant spike immunofluorescent assay, and spike pseudoparticle neutralisation and microneutralisation assay.<xref rid="bib87" ref-type="bibr">87</xref>, <xref rid="bib88" ref-type="bibr">88</xref>, <xref rid="bib89" ref-type="bibr">89</xref>, <xref rid="bib90" ref-type="bibr">90</xref> A case confirmed by serology requires evidence of seroconversion in two samples, ideally taken at least 14 days apart, by a screening (eg, ELISA, immunofluorescence assay) and a neutralisation assay.<xref rid="bib77" ref-type="bibr">77</xref>, <xref rid="bib78" ref-type="bibr">78</xref></p></sec><sec id="cesec180"><title>Imaging</title><p id="para1710">A range of abnormal but non-specific chest x-ray findings are seen in patients with MERS.<xref rid="bib91" ref-type="bibr">91</xref>, <xref rid="bib92" ref-type="bibr">92</xref> These abnormalities include unilateral or bilateral bronchovascular shadowing, interstitial infiltrates, reticular opacities, reticulonodular shadowing, nodules, pleural effusions, and patchy to confluent consolidation (<xref rid="sec1" ref-type="sec">appendix pp 18–19</xref>). Lower lobes tend to be affected more than upper lobes early in the course of MERS and rapid opacification of lungs and progression to acute respiratory distress syndrome can occur.</p><p id="para1720">High-resolution CT might show ground glass opacities (<xref rid="fig5" ref-type="fig">figure 5B</xref>) in early CT findings (with or without consolidation) followed by interlobular septal and intralobular interstitial thickening with peripheral and lower lobe involvement<xref rid="bib93" ref-type="bibr">93</xref>, <xref rid="bib94" ref-type="bibr">94</xref> within the first week of MERS-CoV infection. During subsequent weeks, a so-called crazy-paving lung abnormality, cavitation, tree-in-bud pattern and centrilobular nodules, constrictive obliterative bronchiolitis, bronchiolitis obliterans, peribronchiolar air-trapping, thickened peripheral bronchioles, and organising pneumonia have been observed.<xref rid="bib95" ref-type="bibr"><sup>95</sup></xref></p></sec><sec id="cesec190"><title>Treatment and management</title><p id="para1730">Currently, there are no specific anti-MERS-CoV therapies available for human use. The mainstay of clinical management of MERS cases is mostly symptom focused, providing supportive care<xref rid="bib10" ref-type="bibr">10</xref>, <xref rid="bib61" ref-type="bibr">61</xref> with pain and fever management, treating concomitant or secondary bacterial infections, and supporting vital organ functions. Mild MERS cases can be managed at home.<xref rid="bib96" ref-type="bibr"><sup>96</sup></xref> Predictive factors for development of pneumonia include older age (>56 years), high fever, thrombocytopenia, lymphopenia, C-reactive protein greater than or equal to 2 mg/dL, and a high viral load in sputum (threshold cycle value of rRT-PCR <28·5).<xref rid="bib10" ref-type="bibr">10</xref>, <xref rid="bib70" ref-type="bibr">70</xref> Respiratory failure and acute kidney injury (with haematuria and proteinuria) are common among patients admitted for hospital care because of the severity of their disease and who require mechanical ventilation, extracorporeal membrane oxygenation, and dialyses.<xref rid="bib10" ref-type="bibr">10</xref>, <xref rid="bib61" ref-type="bibr">61</xref>, <xref rid="bib70" ref-type="bibr">70</xref></p><p id="para1740">Several empirical treatments have been studied in severely ill patients. Therapies used for severely ill patients with MERS have included convalescent plasma, corticosteroids, antiviral agents (eg, interferons and ribavirin), and protease inhibitors, or combination of members from these groups. A systematic review of 30 publications on therapeutic agents used for MERS treatment in various outbreaks showed a complete absence of an accurate evidence base and emphasised the need for controlled trials.<xref rid="bib97" ref-type="bibr"><sup>97</sup></xref></p><sec id="cesec200"><title>Antiviral agents</title><p id="para1750">Several agents have shown inhibitory effects against MERS-CoV in cell cultures, including interferons, ribavirin, ciclosporin, and mycophenolic acid.<xref rid="bib98" ref-type="bibr">98</xref>, <xref rid="bib99" ref-type="bibr">99</xref>, <xref rid="bib100" ref-type="bibr">100</xref>, <xref rid="bib101" ref-type="bibr">101</xref>, <xref rid="bib102" ref-type="bibr">102</xref>, <xref rid="bib103" ref-type="bibr">103</xref>, <xref rid="bib104" ref-type="bibr">104</xref>, <xref rid="bib105" ref-type="bibr">105</xref> Empirical lopinavir–ritonavir, pegylated interferon alfa-2a, and ribavirin have been used for serious cases, but no efficacy data are yet available. There is an ongoing randomised clinical trial in progress in Saudi Arabia (the MIRACLE trial; <ext-link ext-link-type="ClinicalTrials.gov" xlink:href="NCT02845843" id="interrefs10">NCT02845843</ext-link>) comparing lopinavir–ritonavir, recombinant interferon beta, and standard supportive care against placebo and standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission. This recursive, multicentre, placebo-controlled, double-blind, randomised controlled trial is designed to include two components, each consisting of two stages. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping (n=34). The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size.</p></sec><sec id="cesec210"><title>Convalescent plasma</title><p id="para1760">The use of plasma from patients with MERS who have made a full recovery (convalescent plasma) requires clinical trial evaluation. Preclinical animal data show that transfer of serum samples from MERS-CoV-immune camels to infected mice resulted in reduced weight loss and lung histopathology,<xref rid="bib106" ref-type="bibr"><sup>106</sup></xref> thus suggesting therapeutic potential. In the 2015 Korean outbreak, three of 13 patients with MERS with respiratory failure were given four infusions of convalescent plasma.<xref rid="bib107" ref-type="bibr"><sup>107</sup></xref> Two of three showed neutralising activity. Donor plasma with a plaque reduction neutralisation test (PRNT) titre of 1/80 had a meaningful serological response after convalescent plasma infusion, while that with a PRNT titre of 1/40 did not. The authors conclude that for effective convalescent plasma infusion in patients with MERS, donor plasma with a neutralisation activity of a PRNT titre greater than or equal to 1/80 should be used.</p></sec><sec id="cesec220"><title>Antibiotic therapy</title><p id="para1770">Antibiotic therapy is commonly started empirically in seriously ill patients. A retrospective study of 136 patients with MERS found that macrolide therapy resulted in no reduction in mortality or faster MERS-CoV RNA clearance compared with those who were not treated with macrolides.<xref rid="bib108" ref-type="bibr"><sup>108</sup></xref></p></sec><sec id="cesec230"><title>Intensive care management</title><p id="para1780">For serious cases, hospital inpatient care is required to reduce the risk of complications such as organ failure and secondary infections. Non-invasive ventilation is associated with a high failure rate (92%) in patients with acute hypoxaemic respiratory failure due to MERS-CoV infection.<xref rid="bib109" ref-type="bibr"><sup>109</sup></xref> Patients with severe symptoms might need to be managed in an intensive care unit, where lung-protective ventilatory strategies for acute respiratory distress syndrome, inotropic support, antimicrobial therapy for co-infections, and renal replacement therapy for acute renal failure can be provided.</p></sec><sec id="cesec240"><title>Systemic corticosteroids</title><p id="para1790">Studies show no benefit from the use of systemic corticosteroids. Systemic corticosteroids were shown to delay viral clearance in critically ill patients with MERS-CoV infection.<xref rid="bib100" ref-type="bibr"><sup>100</sup></xref></p></sec><sec id="cesec250"><title>New treatments</title><p id="para1800">A range of potential treatments are under consideration, development, or evaluation (<xref rid="box3" ref-type="boxed-text">panel 3</xref>). A phase 1, first-in-human, single site, randomised, double-blind, placebo-controlled study to evaluate the safety, tolerability, pharmacokinetics, and immunogenicity of single ascending doses of a co-administered monoclonal antibodies REGN3048 and REGN3051 administered intravenously in healthy adult volunteers (<ext-link ext-link-type="ClinicalTrials.gov" xlink:href="NCT03301090" id="interrefs20">NCT03301090</ext-link>) is ongoing and study duration will be approximately 16 months. Another study is comparing patients who received extracorporeal membrane oxygenation (ECMO) support with those who did not receive ECMO support (<ext-link ext-link-type="ClinicalTrials.gov" xlink:href="NCT02627378" id="interrefs30">NCT02627378</ext-link>). Several monoclonal and polyclonal neutralising antibody products, including novel chimeric camel or human heavy-chain antibodies, are protective in animal models,<xref rid="bib110" ref-type="bibr">110</xref>, <xref rid="bib111" ref-type="bibr">111</xref>, <xref rid="bib112" ref-type="bibr">112</xref> and their potential use for pre-exposure or post-exposure prophylaxis in outbreak management requires evaluations in controlled trials.<boxed-text id="box3"><label>Panel 3</label><caption><title>Potential therapies for the treatment of MERS coronavirus infection97–105, 139–143</title></caption><p id="para470"><bold>Antibody-based interventions</bold></p><p id="para480"><list list-type="simple" id="celist80"><list-item id="celistitem310"><label>•</label><p id="para490">Whole blood</p></list-item><list-item id="celistitem320"><label>•</label><p id="para500">Convalescent plasma</p></list-item><list-item id="celistitem330"><label>•</label><p id="para510">Intravenous immunoglobulin</p></list-item><list-item id="celistitem340"><label>•</label><p id="para520">Polyclonal human immunoglobulin (SAB-301) from transgenic cows</p></list-item><list-item id="celistitem350"><label>•</label><p id="para530">Equine antibody fragments</p></list-item><list-item id="celistitem360"><label>•</label><p id="para540">Camel antibodies</p></list-item><list-item id="celistitem370"><label>•</label><p id="para550">Monoclonal antibodies (eg, MERS-4, MERS-7)</p></list-item><list-item id="celistitem380"><label>•</label><p id="para560">Human monoclonal antibodies to Sprotein</p></list-item><list-item id="celistitem390"><label>•</label><p id="para570">Humanised anti-S monoclonals (eg, hMS-1, m336, 4C2)</p></list-item></list></p><p id="para580"><bold>Interferons</bold></p><p id="para590"><list list-type="simple" id="celist90"><list-item id="celistitem400"><label>•</label><p id="para600">Interferon alfa (1a, 2b)</p></list-item><list-item id="celistitem410"><label>•</label><p id="para610">Interferon beta-1b</p></list-item><list-item id="celistitem420"><label>•</label><p id="para620">Interferon gamma</p></list-item></list></p><p id="para630"><bold>Antivirals</bold></p><p id="para640"><list list-type="simple" id="celist100"><list-item id="celistitem430"><label>•</label><p id="para650">Ribavirin monotherapy (with or without interferon)</p></list-item><list-item id="celistitem440"><label>•</label><p id="para660">HIV protease inhibitors (eg, lopinavir, nelfinavir)</p></list-item><list-item id="celistitem450"><label>•</label><p id="para670">Cyclophilin inhibitors (eg, ciclosporin, alisporivir)</p></list-item><list-item id="celistitem460"><label>•</label><p id="para680">Nucleoside viral RNA polymerase inhibitors (galidesivir, remdesivir, EIDD 2801 [prodrug of EIDD 1931]</p></list-item></list></p><p id="para690"><bold>MERS-CoV 3C-like protease inhibitors</bold></p><p id="para700"><list list-type="simple" id="celist110"><list-item id="celistitem470"><label>•</label><p id="para710">Flavinoids (eg, herbacetin, isobavachalcone, quercetin 3-β-d-glucoside, helichrysetin)</p></list-item></list></p><p id="para720"><bold>Combination therapies</bold></p><p id="para730"><list list-type="simple" id="celist120"><list-item id="celistitem480"><label>•</label><p id="para740">Lopinavir-ritonavir and interferon beta 1b</p></list-item><list-item id="celistitem490"><label>•</label><p id="para750">Cyclosporin plus interferon alpha</p></list-item><list-item id="celistitem500"><label>•</label><p id="para760">Lopinavir-ritonavir</p></list-item><list-item id="celistitem510"><label>•</label><p id="para770">Ribavirin and interferon alpha</p></list-item></list></p><p id="para780"><bold>Host-directed therapies (repurposed drugs)</bold></p><p id="para790"><list list-type="simple" id="celist130"><list-item id="celistitem520"><label>•</label><p id="para800">Chlorpromazine</p></list-item><list-item id="celistitem530"><label>•</label><p id="para810">Mycophenolic acid (with or without interferon beta 1b)</p></list-item><list-item id="celistitem540"><label>•</label><p id="para820">Nitazoxanide</p></list-item><list-item id="celistitem550"><label>•</label><p id="para830">Sitagliptin</p></list-item><list-item id="celistitem560"><label>•</label><p id="para840">Omacetaxine mepesuccinate</p></list-item><list-item id="celistitem570"><label>•</label><p id="para850">Aciclovir</p></list-item><list-item id="celistitem580"><label>•</label><p id="para860">Imatinib mesylate (tyrosine mesylate inhibitor)</p></list-item><list-item id="celistitem590"><label>•</label><p id="para870">Neurotransmitter inhibitors (eg, clomipramine, astemizole)</p></list-item><list-item id="celistitem600"><label>•</label><p id="para880">Neutriceuticals (eg, zinc)</p></list-item></list></p><p id="para890"><bold>Host-directed therapies (cellular therapy)</bold></p><p id="para900"><list list-type="simple" id="celist140"><list-item id="celistitem610"><label>•</label><p id="para910">Allogeneic mesenchymal stromal cells</p></list-item></list></p><p id="para920"><bold>Lectins</bold></p><p id="para930"><list list-type="simple" id="celist150"><list-item id="celistitem620"><label>•</label><p id="para940">Mannose binding lectin</p></list-item></list></p><p id="para950"><bold>Anti-coronavirus peptides</bold></p><p id="para960"><list list-type="simple" id="celist160"><list-item id="celistitem630"><label>•</label><p id="para970">Peptides derived from HR1, HR2, and RBD spike protein subunits</p></list-item><list-item id="celistitem640"><label>•</label><p id="para980">Peptides inhibiting viral entry and replication</p></list-item><list-item id="celistitem650"><label>•</label><p id="para990">Peptides derived from antimicrobial peptides</p></list-item></list></p><p id="para1000"><bold>RNA interference molecules silencing key MERS-CoV genes</bold></p><p id="para1010"><list list-type="simple" id="celist170"><list-item id="celistitem660"><label>•</label><p id="para1020">miRNA molecules</p></list-item><list-item id="celistitem670"><label>•</label><p id="para1030">siRNA molecules</p></list-item></list></p><p id="para1040">MERS=Middle East respiratory syndrome. MERS-CoV=Middle East respiratory syndrome coronavirus. RBD=receptor-binding domain. S=spike. RNA=ribonucleic acid. miRNA=micro RNA. siRNA=small interfering RNA.</p></boxed-text></p></sec><sec id="cesec260"><title>Mental health support</title><p id="para1810">In a mental health study, 7·6% of 1656 patients who were quarantined showed symptoms of anxiety, and 6·4% reported feelings of anger during the 2 weeks of quarantine.<xref rid="bib113" ref-type="bibr"><sup>113</sup></xref> Mental health support, accurate information, and appropriate supplies, including food, clothes, and accommodation, should be provided to people who feel isolated.</p></sec><sec id="cesec270"><title>Management outcomes and mortality rates</title><p id="para1820">Several studies have reported disease severity and mortality risk factor data from patients in the Middle East and South Korea.<xref rid="bib11" ref-type="bibr">11</xref>, <xref rid="bib12" ref-type="bibr">12</xref>, <xref rid="bib21" ref-type="bibr">21</xref>, <xref rid="bib114" ref-type="bibr">114</xref>, <xref rid="bib115" ref-type="bibr">115</xref>, <xref rid="bib116" ref-type="bibr">116</xref>, <xref rid="bib117" ref-type="bibr">117</xref> Ahmed and colleagues collected the daily information on MERS-CoV cases posted online by the Saudi Arabian Ministry of Health between Dec 2, 2014, and Nov 12, 2016, and reviewed 660 laboratory-confirmed cases of MERS.<xref rid="bib114" ref-type="bibr"><sup>114</sup></xref> They showed mortality at day 3 (13·8%), day 30 (28·3%), and overall (29·8%). Patients older than 60 years were more likely to die (45·2% mortality) from their infections than were younger patients (20%).</p><p id="para1830">Several factors are associated with severe disease and high mortality rates in patients with MERS. These factors include male sex, comorbid pre-existing illnesses (such as obesity, diabetes mellitus, cancer, chronic heart, lung, and kidney disease, and immunocompromised states), low serum albumin, thrombocytopenia, lymphopenia, concomitant infections, and positive plasma MERS-CoV RNA. DPP4 receptors are upregulated in the lungs of smokers and patients with chronic obstructive pulmonary disease, which might explain why patients with comorbid lung diseases are prone to severe illness.<xref rid="bib118" ref-type="bibr"><sup>118</sup></xref> In the 2015 Korean outbreak, the case-fatality rate was 20·4% (39 of 186 patients died), the in-hospital mortality was 19·4% (36 of 186 patients), 7-day mortality (from symptom onset) was 3·8% (seven of 186), and 28-day mortality was 17·7% (33 of 186).<xref rid="bib11" ref-type="bibr">11</xref>, <xref rid="bib12" ref-type="bibr">12</xref> Host factors associated with mortality in this outbreak were older age (>60 years), smoking history, pre-existing pneumonia, abnormal renal function, and comorbidity. Low albumin, altered mentality, and high pneumonia severity index score at admission were risk factors for mortality.</p></sec><sec id="cesec280"><title>Prognosis and long term follow-up of MERS survivors</title><p id="para1840">In a study of long-term effects after recovery from MERS,<xref rid="bib119" ref-type="bibr"><sup>119</sup></xref> patients with severe illness who were admitted to intensive care reported higher limitations in some measure of their quality of life than patients with less severe illness who were managed in medical wards. The long-term consequences of MERS illness on survivors appear to be similar to those caused by other viral causes of severe acute respiratory infections such as influenza, parainfluenza, and metapneumovirus.<xref rid="bib120" ref-type="bibr"><sup>120</sup></xref> Follow-up imaging studies of patients who recover from MERS indicate that lung fibrosis might develop in a substantial number of patients.<xref rid="bib95" ref-type="bibr"><sup>95</sup></xref></p></sec></sec><sec id="cesec290"><title>Prevention</title><p id="para1850">The prevention of transmission of MERS-CoV in the community and in health-care settings is crucial to preventing outbreaks and further spread. Several substantive reviews and WHO guidelines are available on the subject.<xref rid="bib21" ref-type="bibr">21</xref>, <xref rid="bib61" ref-type="bibr">61</xref>, <xref rid="bib76" ref-type="bibr">76</xref>, <xref rid="bib96" ref-type="bibr">96</xref></p><p id="para1860">It is important to maintain good personal and environmental hygiene, and to implement stringent contact and droplet precautions among health-care workers. To prevent community transmission, contact tracing, quarantine or isolation of close contacts, and public education are important measures.<xref rid="bib20" ref-type="bibr">20</xref>, <xref rid="bib60" ref-type="bibr">60</xref></p><p id="para1870">In hospitals, early case detection followed by isolation is essential, ideally in negative pressure isolation rooms. The main infection prevention and control measures for managing patients with MERS are well documented from the SARS epidemic and from experiences from managing MERS outbreaks (<xref rid="sec1" ref-type="sec">appendix pp 7–8</xref>).</p><sec id="cesec300"><title>Advances in vaccine development</title><p id="para1880">Advances in technology, vaccine platforms, clinical trial designs, and bioinformatics are supporting MERS-CoV vaccine development (<xref rid="sec1" ref-type="sec">appendix pp 8–9</xref>). WHO target product profiles for MERS-CoV vaccines calls for the development of three types of MERS vaccines: a human vaccine for long-term protection of people at high exposure risk, such as health-care workers and those working with potentially infected camels; a human vaccine for reactive use in outbreak settings; and a dromedary camel vaccine to prevent zoonotic transmission.<xref rid="bib121" ref-type="bibr"><sup>121</sup></xref> Multiple types of vaccine candidates are in development including inactivated whole virus, live attenuated virus, viral vectored vaccines, subunit vaccines, and DNA vaccines.<xref rid="bib121" ref-type="bibr">121</xref>, <xref rid="bib122" ref-type="bibr">122</xref> Most vaccines use the S protein or the domain of the S protein required for binding to host DPP4 as an immunogen, since neutralising antibodies are mostly directed to the receptor binding domain.</p></sec><sec id="cesec310"><title>Priorities for MERS research, surveillance, management, and control</title><p id="para1890">WHO, Food and Agriculture Organization of the UN, and World Organization for Animal Health, in consultation with global MERS community, identified knowledge gaps and priorities for MERS research, surveillance, management, and control (<xref rid="box4" ref-type="boxed-text">panel 4</xref>).<xref rid="bib31" ref-type="bibr"><sup>31</sup></xref><boxed-text id="box4"><label>Panel 4</label><caption><title>Priorities for MERS research, surveillance, management, and control</title></caption><p id="para1050"><bold>Establishing a One Health global consortium:</bold></p><p id="para1060"><list list-type="simple" id="celist180"><list-item id="celistitem680"><label>•</label><p id="para1070">Creation of a One Health multidisciplinary consortia in Middle Eastern and African countries to tackle zoonotic spread of MERS-CoV between animals, humans, and the environment and to monitor, respond to, and prevent major outbreaks</p></list-item><list-item id="celistitem690"><label>•</label><p id="para1080">Establishing effective One Health research and surveillance collaborations between a range of expertise including public health officers, physicians, veterinarians, animal husbandry specialists, agriculturalists, ecologists, phylogeneticists, trialists, and basic scientists</p></list-item></list></p><p id="para1090"><bold>Priority studies in dromedary camels:</bold></p><p id="para1100"><list list-type="simple" id="celist190"><list-item id="celistitem700"><label>•</label><p id="para1110">Natural history studies that evaluate evidence of re-infection</p></list-item><list-item id="celistitem710"><label>•</label><p id="para1120">Value chain and production system analyses</p></list-item><list-item id="celistitem720"><label>•</label><p id="para1130">Improving surveillance to evaluate any seasonal or temporal variation in viral shedding</p></list-item><list-item id="celistitem730"><label>•</label><p id="para1140">Identifying important points for interventions and interruption of within-species and zoonotic transmission</p></list-item><list-item id="celistitem740"><label>•</label><p id="para1150">Accelerating the development of camel vaccine candidates</p></list-item></list></p><p id="para1160"><bold>Priority studies at the animal–human–environmental interface:</bold></p><p id="para1170"><list list-type="simple" id="celist200"><list-item id="celistitem750"><label>•</label><p id="para1180">Real-time mapping of virus circulation and geographical range of MERS-CoV infection in humans and dromedary camels</p></list-item><list-item id="celistitem760"><label>•</label><p id="para1190">Development of new accurate and accessible point-of-care diagnostic tests for outbreak containment, case management, and surveillance</p></list-item><list-item id="celistitem770"><label>•</label><p id="para1200">Evaluating geographical extent of spillover from animals to humans in Africa, the Middle East, and south Asia</p></list-item><list-item id="celistitem780"><label>•</label><p id="para1210">Animal and human serological, virological, and genomic studies in specific locations to evaluate risk factors for human infection and exact routes of zoonotic transmission, including food and oral routes</p></list-item><list-item id="celistitem790"><label>•</label><p id="para1220">Social science and anthropological studies to describe and quantify exposures to dromedary camels and identify opportunities for risk-mitigating interventions</p></list-item></list></p><p id="para1230"><bold>Priority studies in human populations:</bold></p><p id="para1240"><list list-type="simple" id="celist210"><list-item id="celistitem800"><label>•</label><p id="para1250">Accelerating research and development, implementation, and evaluation of medical countermeasures to reduce morbidity and mortality associated with MERS (especially in high risk comorbid populations)</p></list-item><list-item id="celistitem810"><label>•</label><p id="para1260">Identifying optimal interventions for reducing infection among health-care workers in hospital settings</p></list-item><list-item id="celistitem820"><label>•</label><p id="para1270">Determining the role of asymptomatic cases in transmission of infections in humans and whether any specific behaviours can result in human infection from non-human sources</p></list-item><list-item id="celistitem830"><label>•</label><p id="para1280">Targeted epidemiological studies in clinical settings to better understand immune response and duration of infectiousness and address the long-term medical and psychological complications in MERS survivors</p></list-item><list-item id="celistitem840"><label>•</label><p id="para1290">Integrating testing for MERS-CoV into existing respiratory disease surveillance systems to identify extent and spectrum of mild infection in the community</p></list-item></list></p><p id="para1300"><bold>Priority studies for vaccines, therapeutics, and rapid diagnostics:</bold></p><p id="para1310"><list list-type="simple" id="celist220"><list-item id="celistitem850"><label>•</label><p id="para1320">Accelerating the development of human MERS-CoV vaccine candidates</p></list-item><list-item id="celistitem860"><label>•</label><p id="para1330">Accelerating development of MERS-CoV therapeutic pipeline and host-directed therapies</p></list-item><list-item id="celistitem870"><label>•</label><p id="para1340">Development of new accurate and accessible diagnostic tests for outbreak containment, case management, and surveillance</p></list-item><list-item id="celistitem880"><label>•</label><p id="para1350">Increased donor investment into research and development for: novel point-of-care testing options, syndromic panels for differential diagnosis, a greater understanding of viral and antibody kinetics, improved access to clinical specimens, and establishment of international reference standards</p></list-item></list></p><p id="para1360">Adapted from the FAO-OIE-WHO MERS Technical Working Group's report on MERS (2018). MERS=Middle East respiratory syndrome. <xref rid="bib31" ref-type="bibr"><sup>31</sup></xref> MERS-CoV=Middle East respiratory syndrome coronavirus.</p></boxed-text></p><p id="para1900">Several recent publications have highlighted the importance of a one-human-environmental-animal-health (One Health) approach to tackle and control the spread of MERS-CoV (<xref rid="sec1" ref-type="sec">appendix p 9</xref>).<xref rid="bib31" ref-type="bibr">31</xref>, <xref rid="bib121" ref-type="bibr">121</xref>, <xref rid="bib122" ref-type="bibr">122</xref>, <xref rid="bib123" ref-type="bibr">123</xref>, <xref rid="bib124" ref-type="bibr">124</xref>, <xref rid="bib125" ref-type="bibr">125</xref>, <xref rid="bib126" ref-type="bibr">126</xref></p></sec></sec><sec id="cesec320"><title>Conclusion</title><p id="para1910">MERS-CoV is a pathogen with epidemic potential that continues to cause sporadic human disease and remains on the WHO Blueprint 2020 priority list.<xref rid="bib4" ref-type="bibr"><sup>4</sup></xref> Given that MERS-CoV appears to be highly endemic among dromedary camels from geographically widespread areas of the Middle East and Africa, zoonotic transmission with consequent risk of human epidemics will most likely continue for years to come.<xref rid="bib8" ref-type="bibr">8</xref>, <xref rid="bib9" ref-type="bibr">9</xref> MERS-CoV endemic and at-risk countries must invest more in surveillance, in public health research, and in medical interventions—including human and camel vaccine development. The continued risk of human MERS-CoV outbreaks 7 years after its first discovery, effective human and camel MERS-CoV vaccines appear to be the ideal way to prevent continuing spread of MERS-CoV in dromedary camels in the Middle East and in humans at high risk of acquiring community and nosocomial MERS-CoV infection.</p></sec><sec id="cesec330"><title>Search strategy and selection criteria</title><p id="para1920"><boxed-text id="cetextbox10"><p id="para1930">We searched publications in the English language literature on PubMed and Google Scholar (dates we used to refine our search: Sept 1, 2012, to Dec 31, 2019). We used the search terms “Middle East Respiratory Syndrome” OR “MERS-CoV” OR “MERS” in combination with the terms “Coronavirus”, OR “Middle East”, OR “Epidemiology”, “Aetiology”, “Dromedaries”, “Camels”, “Bats”, OR “Transmission”, OR “Virology” OR “Pathogenesis”, “Clinical features” OR “Infection control”, “Diagnostic tests”, OR “Diagnosis” OR “Treatment”, OR “Management”, OR “drugs”, “Therapies”, OR “Prevention” OR “Vaccines” OR “Nosocomial” OR “Hospital”. We also searched websites of global and national public health agencies such as WHO, WHO–Regional Office for the Eastern Mediterranean, UN Food and Agriculture Organization, US Centers for Disease Control and Prevention (CDC), Public Health England (UK), World Organisation for Animal Health, European Centre for Disease Prevention and Control (ECDC), and the Saudi Ministry of Health Middle East respiratory syndrome (MERS) portal. We reviewed publications on MERS from WHO, CDC, ECDC, Center for Infectious Disease Research and Policy (University of Minnesota, USA), and ProMED (Program for Monitoring Emerging Diseases) websites. We focused our review on publications published in the past 36 months to update the <italic>Lancet</italic> Seminar on MERS published in September, 2015. We also selected reference lists and substantive reviews of articles identified by this search strategy that we judged relevant to provide readers with additional details and more references than this Seminar can accommodate.</p></boxed-text></p></sec></body><back><ref-list id="bibl10"><title>References</title><ref id="bib1"><label>1</label><element-citation publication-type="other" id="sbref10"><person-group person-group-type="author"><collab>WHO</collab></person-group><article-title>SARS (severe acute respiratory syndrome)</article-title><ext-link ext-link-type="uri" xlink:href="https://www.who.int/ith/diseases/sars/en/" id="interrefs40">https://www.who.int/ith/diseases/sars/en/</ext-link></element-citation></ref><ref id="bib2"><label>2</label><element-citation publication-type="other" id="sbref20"><person-group person-group-type="author"><collab>WHO</collab></person-group><article-title>Middle East respiratory syndrome coronavirus (MERS-CoV)</article-title><ext-link ext-link-type="uri" xlink:href="https://www.who.int/emergencies/mers-cov/en/" id="interrefs50">https://www.who.int/emergencies/mers-cov/en/</ext-link></element-citation></ref><ref id="bib3"><label>3</label><element-citation publication-type="other" id="sbref30"><person-group person-group-type="author"><collab>WHO</collab></person-group><article-title>Coronavirus disease (COVID-19) outbreak</article-title><ext-link ext-link-type="uri" xlink:href="https://www.who.int/emergencies/diseases/novel-coronavirus-2019" id="interrefs60">https://www.who.int/emergencies/diseases/novel-coronavirus-2019</ext-link></element-citation></ref><ref id="bib4"><label>4</label><element-citation publication-type="other" id="sbref40"><person-group person-group-type="author"><collab>WHO</collab></person-group><article-title>A research and development blueprint for action to prevent epidemics</article-title><ext-link ext-link-type="uri" xlink:href="https://www.who.int/blueprint/en/" id="interrefs70">https://www.who.int/blueprint/en/</ext-link></element-citation></ref><ref id="bib5"><label>5</label><element-citation publication-type="journal" id="sbref50"><person-group person-group-type="author"><name><surname>Peiris</surname><given-names>JS</given-names></name><name><surname>Yuen</surname><given-names>KY</given-names></name><name><surname>Osterhaus</surname><given-names>AD</given-names></name><name><surname>Stöhr</surname><given-names>K</given-names></name></person-group><article-title>The severe acute respiratory syndrome</article-title><source>N Engl J Med</source><volume>349</volume><year>2003</year><fpage>2431</fpage><lpage>2441</lpage><pub-id pub-id-type="pmid">14681510</pub-id></element-citation></ref><ref id="bib6"><label>6</label><element-citation publication-type="journal" id="sbref60"><person-group person-group-type="author"><name><surname>Zaki</surname><given-names>AM</given-names></name><name><surname>van Boheemen</surname><given-names>S</given-names></name><name><surname>Bestebroer</surname><given-names>TM</given-names></name><name><surname>Osterhaus</surname><given-names>AD</given-names></name><name><surname>Fouchier</surname><given-names>RA</given-names></name></person-group><article-title>Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia</article-title><source>N Engl J Med</source><volume>367</volume><year>2012</year><fpage>1814</fpage><lpage>1820</lpage><pub-id pub-id-type="pmid">23075143</pub-id></element-citation></ref><ref id="bib7"><label>7</label><element-citation publication-type="journal" id="sbref70"><person-group person-group-type="author"><name><surname>Hijawi</surname><given-names>B</given-names></name><name><surname>Abdallat</surname><given-names>M</given-names></name><name><surname>Sayaydeh</surname><given-names>A</given-names></name></person-group><article-title>Novel coronavirus infections in Jordan, April 2012: epidemiological findings from a retrospective investigation</article-title><source>East Mediterr Health J</source><volume>19</volume><year>2013</year><fpage>S12</fpage><lpage>S18</lpage><pub-id pub-id-type="pmid">23888790</pub-id></element-citation></ref><ref id="bib8"><label>8</label><element-citation publication-type="journal" id="sbref80"><person-group person-group-type="author"><name><surname>Drosten</surname><given-names>C</given-names></name><name><surname>Kellam</surname><given-names>P</given-names></name><name><surname>Memish</surname><given-names>ZA</given-names></name></person-group><article-title>Evidence for camel-to-human transmission of MERS coronavirus</article-title><source>N Engl J Med</source><volume>371</volume><year>2014</year><fpage>1359</fpage><lpage>1360</lpage><pub-id pub-id-type="pmid">25271615</pub-id></element-citation></ref><ref id="bib9"><label>9</label><element-citation publication-type="journal" id="sbref90"><person-group person-group-type="author"><name><surname>El-Kafrawy</surname><given-names>SA</given-names></name><name><surname>Corman</surname><given-names>VM</given-names></name><name><surname>Tolah</surname><given-names>AM</given-names></name></person-group><article-title>Enzootic patterns of Middle East respiratory syndrome coronavirus in imported African and local Arabian dromedary camels: a prospective genomic study</article-title><source>Lancet Planet Health</source><volume>3</volume><year>2019</year><fpage>e521</fpage><lpage>e528</lpage><pub-id pub-id-type="pmid">31843456</pub-id></element-citation></ref><ref id="bib10"><label>10</label><element-citation publication-type="journal" id="sbref100"><person-group person-group-type="author"><name><surname>Zumla</surname><given-names>A</given-names></name><name><surname>Hui</surname><given-names>DS</given-names></name><name><surname>Perlman</surname><given-names>S</given-names></name></person-group><article-title>Middle East respiratory syndrome</article-title><source>Lancet</source><volume>386</volume><year>2015</year><fpage>995</fpage><lpage>1007</lpage><pub-id pub-id-type="pmid">26049252</pub-id></element-citation></ref><ref id="bib11"><label>11</label><element-citation publication-type="journal" id="sbref110"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>KH</given-names></name><name><surname>Tandi</surname><given-names>TE</given-names></name><name><surname>Choi</surname><given-names>JW</given-names></name><name><surname>Moon</surname><given-names>JM</given-names></name><name><surname>Kim</surname><given-names>MS</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak in South Korea, 2015: epidemiology, characteristics and public health implications</article-title><source>J Hosp Infect</source><volume>95</volume><year>2017</year><fpage>207</fpage><lpage>213</lpage><pub-id pub-id-type="pmid">28153558</pub-id></element-citation></ref><ref id="bib12"><label>12</label><element-citation publication-type="journal" id="sbref120"><person-group person-group-type="author"><name><surname>Oh</surname><given-names>MD</given-names></name><name><surname>Park</surname><given-names>WB</given-names></name><name><surname>Park</surname><given-names>SW</given-names></name></person-group><article-title>Middle East respiratory syndrome: what we learned from the 2015 outbreak in the Republic of Korea</article-title><source>Korean J Intern Med</source><volume>33</volume><year>2018</year><fpage>233</fpage><lpage>246</lpage><pub-id pub-id-type="pmid">29506344</pub-id></element-citation></ref><ref id="bib13"><label>13</label><element-citation publication-type="journal" id="sbref130"><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></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><comment>published online January 24.</comment><pub-id pub-id-type="doi">10.1056/NEJMoa2001017</pub-id></element-citation></ref><ref id="bib14"><label>14</label><element-citation publication-type="book" id="sbref140"><person-group person-group-type="author"><name><surname>Masters</surname><given-names>PS</given-names></name><name><surname>Perlman</surname><given-names>S</given-names></name></person-group><chapter-title>Coronaviridae</chapter-title><person-group person-group-type="editor"><name><surname>Knipe</surname><given-names>DM</given-names></name><name><surname>Howley</surname><given-names>PM</given-names></name></person-group><source>Fields virology</source><year>2013</year><publisher-name>Lippincott Williams & Wilkins</publisher-name><publisher-loc>Philadelphia, PA</publisher-loc><fpage>825</fpage><lpage>858</lpage></element-citation></ref><ref id="bib15"><label>15</label><element-citation publication-type="journal" id="sbref150"><person-group person-group-type="author"><name><surname>Raj</surname><given-names>VS</given-names></name><name><surname>Mou</surname><given-names>H</given-names></name><name><surname>Smits</surname><given-names>SL</given-names></name></person-group><article-title>Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC</article-title><source>Nature</source><volume>495</volume><year>2013</year><fpage>251</fpage><lpage>254</lpage><pub-id pub-id-type="pmid">23486063</pub-id></element-citation></ref><ref id="bib16"><label>16</label><element-citation publication-type="journal" id="sbref160"><person-group person-group-type="author"><name><surname>Walls</surname><given-names>AC</given-names></name><name><surname>Tortorici</surname><given-names>MA</given-names></name><name><surname>Bosch</surname><given-names>BJ</given-names></name></person-group><article-title>Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimer</article-title><source>Nature</source><volume>531</volume><year>2016</year><fpage>114</fpage><lpage>117</lpage><pub-id pub-id-type="pmid">26855426</pub-id></element-citation></ref><ref id="bib17"><label>17</label><element-citation publication-type="journal" id="sbref170"><person-group person-group-type="author"><name><surname>Yuan</surname><given-names>Y</given-names></name><name><surname>Cao</surname><given-names>D</given-names></name><name><surname>Zhang</surname><given-names>Y</given-names></name></person-group><article-title>Cryo-em structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains</article-title><source>Nat Commun</source><volume>8</volume><year>2017</year><object-id pub-id-type="publisher-id">15092</object-id></element-citation></ref><ref id="bib18"><label>18</label><element-citation publication-type="journal" id="sbref180"><person-group person-group-type="author"><name><surname>Fehr</surname><given-names>AR</given-names></name><name><surname>Perlman</surname><given-names>S</given-names></name></person-group><article-title>Coronaviruses: an overview of their replication and pathogenesis</article-title><source>Methods Mol Biol</source><volume>1282</volume><year>2015</year><fpage>1</fpage><lpage>23</lpage><pub-id pub-id-type="pmid">25720466</pub-id></element-citation></ref><ref id="bib19"><label>19</label><element-citation publication-type="other" id="sbref190"><person-group person-group-type="author"><collab>WHO</collab></person-group><article-title>Middle East respiratory syndrome coronavirus: case definition for reporting to WHO</article-title><ext-link ext-link-type="uri" xlink:href="https://www.who.int/csr/disease/coronavirus_infections/case_definition/en/" id="interrefs90">https://www.who.int/csr/disease/coronavirus_infections/case_definition/en/</ext-link></element-citation></ref><ref id="bib20"><label>20</label><element-citation publication-type="journal" id="sbref200"><person-group person-group-type="author"><name><surname>Conzade</surname><given-names>R</given-names></name><name><surname>Grant</surname><given-names>R</given-names></name><name><surname>Malik</surname><given-names>MR</given-names></name></person-group><article-title>Reported direct and indirect contact with dromedary camels among laboratory-confirmed MERS-CoV cases</article-title><source>Viruses</source><volume>10</volume><year>2018</year><fpage>425</fpage></element-citation></ref><ref id="bib21"><label>21</label><element-citation publication-type="journal" id="sbref210"><person-group person-group-type="author"><name><surname>Hui</surname><given-names>DS</given-names></name><name><surname>Azhar</surname><given-names>EI</given-names></name><name><surname>Kim</surname><given-names>YJ</given-names></name><name><surname>Memish</surname><given-names>ZA</given-names></name><name><surname>Oh</surname><given-names>MD</given-names></name><name><surname>Zumla</surname><given-names>A</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus: risk factors and determinants of primary, household, and nosocomial transmission</article-title><source>Lancet Infect Dis</source><volume>18</volume><year>2018</year><fpage>e217</fpage><lpage>e227</lpage><pub-id pub-id-type="pmid">29680581</pub-id></element-citation></ref><ref id="bib22"><label>22</label><element-citation publication-type="journal" id="sbref220"><person-group person-group-type="author"><name><surname>Kandeil</surname><given-names>A</given-names></name><name><surname>Gomaa</surname><given-names>M</given-names></name><name><surname>Nageh</surname><given-names>A</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels in Africa and Middle East</article-title><source>Viruses</source><volume>11</volume><year>2019</year><fpage>717</fpage></element-citation></ref><ref id="bib23"><label>23</label><element-citation publication-type="journal" id="sbref230"><person-group person-group-type="author"><name><surname>Reusken</surname><given-names>CB</given-names></name><name><surname>Ababneh</surname><given-names>M</given-names></name><name><surname>Raj</surname><given-names>VS</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus (MERS-CoV) serology in major livestock species in an affected region in Jordan, June to September 2013</article-title><source>Euro Surveill</source><volume>18</volume><year>2013</year><object-id pub-id-type="publisher-id">20662</object-id></element-citation></ref><ref id="bib24"><label>24</label><element-citation publication-type="journal" id="sbref240"><person-group person-group-type="author"><name><surname>Azhar</surname><given-names>EI</given-names></name><name><surname>El-Kafrawy</surname><given-names>SA</given-names></name><name><surname>Farraj</surname><given-names>SA</given-names></name></person-group><article-title>Evidence for camel-to-human transmission of MERS coronavirus</article-title><source>N Engl J Med</source><volume>370</volume><year>2014</year><fpage>2499</fpage><lpage>2505</lpage><pub-id pub-id-type="pmid">24896817</pub-id></element-citation></ref><ref id="bib25"><label>25</label><element-citation publication-type="journal" id="sbref250"><person-group person-group-type="author"><name><surname>Haagmans</surname><given-names>BL</given-names></name><name><surname>Al Dhahiry</surname><given-names>SH</given-names></name><name><surname>Reusken</surname><given-names>CB</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus in dromedary camels: an outbreak investigation</article-title><source>Lancet Infect Dis</source><volume>14</volume><year>2014</year><fpage>140</fpage><lpage>145</lpage><pub-id pub-id-type="pmid">24355866</pub-id></element-citation></ref><ref id="bib26"><label>26</label><element-citation publication-type="journal" id="sbref260"><person-group person-group-type="author"><name><surname>Paden</surname><given-names>CR</given-names></name><name><surname>Yusof</surname><given-names>M</given-names></name><name><surname>Al Hammadi</surname><given-names>ZM</given-names></name></person-group><article-title>Zoonotic origin and transmission of Middle East respiratory syndrome coronavirus in the UAE</article-title><source>Zoonoses Public Health</source><volume>65</volume><year>2018</year><fpage>322</fpage><lpage>333</lpage><pub-id pub-id-type="pmid">29239118</pub-id></element-citation></ref><ref id="bib27"><label>27</label><element-citation publication-type="journal" id="sbref270"><person-group person-group-type="author"><name><surname>Adney</surname><given-names>DR</given-names></name><name><surname>van Doremalen</surname><given-names>N</given-names></name><name><surname>Brown</surname><given-names>VR</given-names></name></person-group><article-title>Replication and shedding of MERS-CoV in upper respiratory tract of inoculated dromedary camels</article-title><source>Emerg Infect Dis</source><volume>20</volume><year>2014</year><fpage>1999</fpage><lpage>2005</lpage><pub-id pub-id-type="pmid">25418529</pub-id></element-citation></ref><ref id="bib28"><label>28</label><element-citation publication-type="journal" id="sbref280"><person-group person-group-type="author"><name><surname>Khalafalla</surname><given-names>AI</given-names></name><name><surname>Lu</surname><given-names>X</given-names></name><name><surname>Al-Mubarak</surname><given-names>AI</given-names></name><name><surname>Dalab</surname><given-names>AH</given-names></name><name><surname>Al-Busadah</surname><given-names>KA</given-names></name><name><surname>Erdman</surname><given-names>DD</given-names></name></person-group><article-title>MERS-CoV in upper respiratory tract and lungs of dromedary camels, Saudi Arabia, 2013–2014</article-title><source>Emerg Infect Dis</source><volume>21</volume><year>2015</year><fpage>1153</fpage><lpage>1158</lpage><pub-id pub-id-type="pmid">26079346</pub-id></element-citation></ref><ref id="bib29"><label>29</label><element-citation publication-type="journal" id="sbref290"><person-group person-group-type="author"><name><surname>Sikkema</surname><given-names>RS</given-names></name><name><surname>Farag</surname><given-names>E</given-names></name><name><surname>Islam</surname><given-names>M</given-names></name></person-group><article-title>Global status of Middle East respiratory syndrome coronavirus in dromedary camels: a systematic review</article-title><source>Epidemiol Infect</source><volume>147</volume><year>2019</year><fpage>e84</fpage><pub-id pub-id-type="pmid">30869000</pub-id></element-citation></ref><ref id="bib30"><label>30</label><element-citation publication-type="journal" id="sbref300"><person-group person-group-type="author"><name><surname>Sabir</surname><given-names>JS</given-names></name><name><surname>Lam</surname><given-names>TT</given-names></name><name><surname>Ahmed</surname><given-names>MM</given-names></name></person-group><article-title>Co-circulation of three camel coronavirus species and recombination of MERS-CoVs in Saudi Arabia</article-title><source>Science</source><volume>351</volume><year>2016</year><fpage>81</fpage><lpage>84</lpage><pub-id pub-id-type="pmid">26678874</pub-id></element-citation></ref><ref id="bib31"><label>31</label><element-citation publication-type="journal" id="sbref310"><person-group person-group-type="author"><collab>FAO-OIE-WHO MERS Technical Working Group</collab></person-group><article-title>MERS: progress on the global response, remaining challenges and the way forward</article-title><source>Antiviral Res</source><volume>159</volume><year>2018</year><fpage>35</fpage><lpage>44</lpage><pub-id pub-id-type="pmid">30236531</pub-id></element-citation></ref><ref id="bib32"><label>32</label><element-citation publication-type="journal" id="sbref320"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>JI</given-names></name><name><surname>Park</surname><given-names>S</given-names></name><name><surname>Bae</surname><given-names>JY</given-names></name><name><surname>Park</surname><given-names>MS</given-names></name></person-group><article-title>Evolutionary relationship analysis of Middle East respiratory syndrome coronavirus 4a and 4b protein coding sequences</article-title><source>J Vet Sci</source><volume>20</volume><year>2019</year><fpage>e1</fpage><pub-id pub-id-type="pmid">30944524</pub-id></element-citation></ref><ref id="bib33"><label>33</label><element-citation publication-type="journal" id="sbref330"><person-group person-group-type="author"><name><surname>Elkholy</surname><given-names>AA</given-names></name><name><surname>Grant</surname><given-names>R</given-names></name><name><surname>Assiri</surname><given-names>A</given-names></name><name><surname>Elhakim</surname><given-names>M</given-names></name><name><surname>Malik</surname><given-names>MR</given-names></name><name><surname>Van Kerkhove</surname><given-names>MD</given-names></name></person-group><article-title>MERS-CoV infection among healthcare workers and risk factors for death: retrospective analysis of all laboratory-confirmed cases reported to WHO from 2012 to 2 June 2018</article-title><source>J Infect Public Health</source><year>2019</year><comment>published online May 2.</comment><pub-id pub-id-type="doi">10.1016/j.jiph.2019.04.011</pub-id></element-citation></ref><ref id="bib34"><label>34</label><element-citation publication-type="journal" id="sbref340"><person-group person-group-type="author"><name><surname>Al Hammadi</surname><given-names>ZM</given-names></name><name><surname>Chu</surname><given-names>DK</given-names></name><name><surname>Eltahir</surname><given-names>YM</given-names></name></person-group><article-title>Asymptomatic MERS-CoV infection in humans possibly linked to infected dromedaries imported from Oman to United Arab Emirates, May 2015</article-title><source>Emerg Infect Dis</source><volume>21</volume><year>2015</year><fpage>2197</fpage><lpage>2200</lpage><pub-id pub-id-type="pmid">26584223</pub-id></element-citation></ref><ref id="bib35"><label>35</label><element-citation publication-type="journal" id="sbref350"><person-group person-group-type="author"><name><surname>Alraddadi</surname><given-names>BM</given-names></name><name><surname>Al-Salmi</surname><given-names>HS</given-names></name><name><surname>Jacobs-Slifka</surname><given-names>K</given-names></name></person-group><article-title>Risk factors for Middle East respiratory syndrome coronavirus infection among healthcare personnel</article-title><source>Emerg Infect Dis</source><volume>22</volume><year>2016</year><fpage>1915</fpage><lpage>1920</lpage><pub-id pub-id-type="pmid">27767011</pub-id></element-citation></ref><ref id="bib36"><label>36</label><element-citation publication-type="journal" id="sbref360"><person-group person-group-type="author"><name><surname>Farag</surname><given-names>EA</given-names></name><name><surname>Reusken</surname><given-names>CB</given-names></name><name><surname>Haagmans</surname><given-names>BL</given-names></name></person-group><article-title>High proportion of MERS-CoV shedding dromedaries at slaughterhouse with a potential epidemiological link to human cases, Qatar 2014</article-title><source>Infect Ecol Epidemiol</source><volume>5</volume><year>2015</year><object-id pub-id-type="publisher-id">28305</object-id></element-citation></ref><ref id="bib37"><label>37</label><element-citation publication-type="journal" id="sbref370"><person-group person-group-type="author"><name><surname>Kasem</surname><given-names>S</given-names></name><name><surname>Qasim</surname><given-names>I</given-names></name><name><surname>Al-Hufofi</surname><given-names>A</given-names></name></person-group><article-title>Cross-sectional study of MERS-CoV-specific RNA and antibodies in animals that have had contact with MERS patients in Saudi Arabia</article-title><source>J Infect Public Health</source><volume>11</volume><year>2018</year><fpage>331</fpage><lpage>338</lpage><pub-id pub-id-type="pmid">28993171</pub-id></element-citation></ref><ref id="bib38"><label>38</label><element-citation publication-type="journal" id="sbref380"><person-group person-group-type="author"><name><surname>Muhairi</surname><given-names>SA</given-names></name><name><surname>Hosani</surname><given-names>FA</given-names></name><name><surname>Eltahir</surname><given-names>YM</given-names></name></person-group><article-title>Epidemiological investigation of Middle East respiratory syndrome coronavirus in dromedary camel farms linked with human infection in Abu Dhabi Emirate, United Arab Emirates</article-title><source>Virus Genes</source><volume>52</volume><year>2016</year><fpage>848</fpage><lpage>854</lpage><pub-id pub-id-type="pmid">27357298</pub-id></element-citation></ref><ref id="bib39"><label>39</label><element-citation publication-type="journal" id="sbref390"><person-group person-group-type="author"><name><surname>Zhou</surname><given-names>J</given-names></name><name><surname>Li</surname><given-names>C</given-names></name><name><surname>Zhao</surname><given-names>G</given-names></name></person-group><article-title>Human intestinal tract serves as an alternative infection route for Middle East respiratory syndrome coronavirus</article-title><source>Sci Adv</source><volume>3</volume><year>2017</year><object-id pub-id-type="publisher-id">eaao4966</object-id></element-citation></ref><ref id="bib40"><label>40</label><element-citation publication-type="journal" id="sbref400"><person-group person-group-type="author"><name><surname>Bernard-Stoecklin</surname><given-names>S</given-names></name><name><surname>Nikolay</surname><given-names>B</given-names></name><name><surname>Assiri</surname><given-names>A</given-names></name></person-group><article-title>Comparative analysis of eleven healthcare-associated outbreaks of Middle East respiratory syndrome coronavirus (MERS-CoV) from 2015 to 2017</article-title><source>Sci Rep</source><volume>9</volume><year>2019</year><object-id pub-id-type="publisher-id">7385</object-id></element-citation></ref><ref id="bib41"><label>41</label><element-citation publication-type="journal" id="sbref410"><person-group person-group-type="author"><name><surname>Choi</surname><given-names>S</given-names></name><name><surname>Jung</surname><given-names>E</given-names></name><name><surname>Choi</surname><given-names>BY</given-names></name><name><surname>Hur</surname><given-names>YJ</given-names></name><name><surname>Ki</surname><given-names>M</given-names></name></person-group><article-title>High reproduction number of Middle East respiratory syndrome coronavirus in nosocomial outbreaks: mathematical modelling in Saudi Arabia and South Korea</article-title><source>J Hosp Infect</source><volume>99</volume><year>2018</year><fpage>162</fpage><lpage>168</lpage><pub-id pub-id-type="pmid">28958834</pub-id></element-citation></ref><ref id="bib42"><label>42</label><element-citation publication-type="journal" id="sbref420"><person-group person-group-type="author"><name><surname>Assiri</surname><given-names>A</given-names></name><name><surname>McGeer</surname><given-names>A</given-names></name><name><surname>Perl</surname><given-names>TM</given-names></name></person-group><article-title>Hospital outbreak of Middle East respiratory syndrome coronavirus</article-title><source>N Engl J Med</source><volume>369</volume><year>2013</year><fpage>407</fpage><lpage>416</lpage><pub-id pub-id-type="pmid">23782161</pub-id></element-citation></ref><ref id="bib43"><label>43</label><element-citation publication-type="journal" id="sbref430"><person-group person-group-type="author"><name><surname>Alanazi</surname><given-names>KH</given-names></name><name><surname>Killerby</surname><given-names>ME</given-names></name><name><surname>Biggs</surname><given-names>HM</given-names></name></person-group><article-title>Scope and extent of healthcare-associated Middle East respiratory syndrome coronavirus transmission during two contemporaneous outbreaks in Riyadh, Saudi Arabia, 2017</article-title><source>Infect Control Hosp Epidemiol</source><volume>40</volume><year>2019</year><fpage>79</fpage><lpage>88</lpage><pub-id pub-id-type="pmid">30595141</pub-id></element-citation></ref><ref id="bib44"><label>44</label><element-citation publication-type="journal" id="sbref440"><person-group person-group-type="author"><name><surname>Amer</surname><given-names>H</given-names></name><name><surname>Alqahtani</surname><given-names>AS</given-names></name><name><surname>Alzoman</surname><given-names>H</given-names></name><name><surname>Aljerian</surname><given-names>N</given-names></name><name><surname>Memish</surname><given-names>ZA</given-names></name></person-group><article-title>Unusual presentation of Middle East respiratory syndrome coronavirus leading to a large outbreak in Riyadh during 2017</article-title><source>Am J Infect Control</source><volume>46</volume><year>2018</year><fpage>1022</fpage><lpage>1025</lpage><pub-id pub-id-type="pmid">29661625</pub-id></element-citation></ref><ref id="bib45"><label>45</label><element-citation publication-type="journal" id="sbref450"><person-group person-group-type="author"><name><surname>Kang</surname><given-names>CK</given-names></name><name><surname>Song</surname><given-names>KH</given-names></name><name><surname>Choe</surname><given-names>PG</given-names></name></person-group><article-title>Clinical and epidemiologic characteristics of spreaders of Middle East respiratory syndrome coronavirus during the 2015 outbreak in Korea</article-title><source>J Korean Med Sci</source><volume>32</volume><year>2017</year><fpage>744</fpage><lpage>749</lpage><pub-id pub-id-type="pmid">28378546</pub-id></element-citation></ref><ref id="bib46"><label>46</label><element-citation publication-type="journal" id="sbref460"><person-group person-group-type="author"><name><surname>Alsaad</surname><given-names>KO</given-names></name><name><surname>Hajeer</surname><given-names>AH</given-names></name><name><surname>Al Balwi</surname><given-names>M</given-names></name></person-group><article-title>Histopathology of Middle East respiratory syndrome coronovirus (MERS-CoV) infection—clinicopathological and ultrastructural study</article-title><source>Histopathology</source><volume>72</volume><year>2018</year><fpage>516</fpage><lpage>524</lpage><pub-id pub-id-type="pmid">28858401</pub-id></element-citation></ref><ref id="bib47"><label>47</label><element-citation publication-type="journal" id="sbref470"><person-group person-group-type="author"><name><surname>Ng</surname><given-names>DL</given-names></name><name><surname>Al Hosani</surname><given-names>F</given-names></name><name><surname>Keating</surname><given-names>MK</given-names></name></person-group><article-title>Clinicopathologic, immunohistochemical, and ultrastructural findings of a fatal case of Middle East respiratory syndrome coronavirus infection in the United Arab Emirates, April 2014</article-title><source>Am J Pathol</source><volume>186</volume><year>2016</year><fpage>652</fpage><lpage>658</lpage><pub-id pub-id-type="pmid">26857507</pub-id></element-citation></ref><ref id="bib48"><label>48</label><element-citation publication-type="journal" id="sbref480"><person-group person-group-type="author"><name><surname>Yeung</surname><given-names>ML</given-names></name><name><surname>Yao</surname><given-names>Y</given-names></name><name><surname>Jia</surname><given-names>L</given-names></name></person-group><article-title>MERS coronavirus induces apoptosis in kidney and lung by upregulating Smad7 and FGF2</article-title><source>Nat Microbiol</source><volume>1</volume><year>2016</year><object-id pub-id-type="publisher-id">16004</object-id></element-citation></ref><ref id="bib49"><label>49</label><element-citation publication-type="journal" id="sbref490"><person-group person-group-type="author"><name><surname>Corman</surname><given-names>VM</given-names></name><name><surname>Albarrak</surname><given-names>AM</given-names></name><name><surname>Omrani</surname><given-names>AS</given-names></name></person-group><article-title>Viral shedding and antibody response in 37 patients with Middle East respiratory syndrome coronavirus infection</article-title><source>Clin Infect Dis</source><volume>62</volume><year>2016</year><fpage>477</fpage><lpage>483</lpage><pub-id pub-id-type="pmid">26565003</pub-id></element-citation></ref><ref id="bib50"><label>50</label><element-citation publication-type="journal" id="sbref500"><person-group person-group-type="author"><name><surname>Widagdo</surname><given-names>W</given-names></name><name><surname>Sooksawasdi Na Ayudhya</surname><given-names>S</given-names></name><name><surname>Hundie</surname><given-names>GB</given-names></name></person-group><article-title>Host determinants of MERS-CoV transmission and pathogenesis</article-title><source>Viruses</source><volume>11</volume><year>2019</year><fpage>E280</fpage><pub-id pub-id-type="pmid">30893947</pub-id></element-citation></ref><ref id="bib51"><label>51</label><element-citation publication-type="journal" id="sbref510"><person-group person-group-type="author"><name><surname>Leist</surname><given-names>SR</given-names></name><name><surname>Cockrell</surname><given-names>AS</given-names></name></person-group><article-title>Genetically engineering a susceptible mouse model for MERS-CoV-induced acute respiratory distress syndrome</article-title><source>Methods Mol Biol</source><volume>2099</volume><year>2020</year><fpage>137</fpage><lpage>159</lpage><pub-id pub-id-type="pmid">31883094</pub-id></element-citation></ref><ref id="bib52"><label>52</label><element-citation publication-type="journal" id="sbref520"><person-group person-group-type="author"><name><surname>Channappanavar</surname><given-names>R</given-names></name><name><surname>Perlman</surname><given-names>S</given-names></name></person-group><article-title>Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology</article-title><source>Semin Immunopathol</source><volume>39</volume><year>2017</year><fpage>529</fpage><lpage>539</lpage><pub-id pub-id-type="pmid">28466096</pub-id></element-citation></ref><ref id="bib53"><label>53</label><element-citation publication-type="journal" id="sbref530"><person-group person-group-type="author"><name><surname>Cameron</surname><given-names>MJ</given-names></name><name><surname>Ran</surname><given-names>L</given-names></name><name><surname>Xu</surname><given-names>L</given-names></name></person-group><article-title>Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome</article-title><source>J Virol</source><volume>81</volume><year>2007</year><fpage>8692</fpage><lpage>8706</lpage><pub-id pub-id-type="pmid">17537853</pub-id></element-citation></ref><ref id="bib54"><label>54</label><element-citation publication-type="journal" id="sbref540"><person-group person-group-type="author"><name><surname>Chu</surname><given-names>H</given-names></name><name><surname>Zhou</surname><given-names>J</given-names></name><name><surname>Wong</surname><given-names>BH</given-names></name></person-group><article-title>Productive replication of Middle East respiratory syndrome coronavirus in monocyte-derived dendritic cells modulates innate immune response</article-title><source>Virology</source><volume>454–455</volume><year>2014</year><fpage>197</fpage><lpage>205</lpage></element-citation></ref><ref id="bib55"><label>55</label><element-citation publication-type="journal" id="sbref550"><person-group person-group-type="author"><name><surname>Lau</surname><given-names>SK</given-names></name><name><surname>Lau</surname><given-names>CC</given-names></name><name><surname>Chan</surname><given-names>KH</given-names></name></person-group><article-title>Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and treatment</article-title><source>J Gen Virol</source><volume>94</volume><year>2013</year><fpage>2679</fpage><lpage>2690</lpage><pub-id pub-id-type="pmid">24077366</pub-id></element-citation></ref><ref id="bib56"><label>56</label><element-citation publication-type="journal" id="sbref560"><person-group person-group-type="author"><name><surname>Zhou</surname><given-names>J</given-names></name><name><surname>Chu</surname><given-names>H</given-names></name><name><surname>Li</surname><given-names>C</given-names></name></person-group><article-title>Active replication of Middle East respiratory syndrome coronavirus and aberrant induction of inflammatory cytokines and chemokines in human macrophages: implications for pathogenesis</article-title><source>J Infect Dis</source><volume>209</volume><year>2014</year><fpage>1331</fpage><lpage>1342</lpage><pub-id pub-id-type="pmid">24065148</pub-id></element-citation></ref><ref id="bib57"><label>57</label><element-citation publication-type="journal" id="sbref570"><person-group person-group-type="author"><name><surname>Shin</surname><given-names>HS</given-names></name><name><surname>Kim</surname><given-names>Y</given-names></name><name><surname>Kim</surname><given-names>G</given-names></name></person-group><article-title>Immune responses to Middle East respiratory syndrome coronavirus during the acute and convalescent phases of human infection</article-title><source>Clin Infect Dis</source><volume>68</volume><year>2019</year><fpage>984</fpage><lpage>992</lpage><pub-id pub-id-type="pmid">30060038</pub-id></element-citation></ref><ref id="bib58"><label>58</label><element-citation publication-type="journal" id="sbref580"><person-group person-group-type="author"><name><surname>Drosten</surname><given-names>C</given-names></name><name><surname>Meyer</surname><given-names>B</given-names></name><name><surname>Müller</surname><given-names>MA</given-names></name></person-group><article-title>Transmission of MERS-coronavirus in household contacts</article-title><source>N Engl J Med</source><volume>371</volume><year>2014</year><fpage>828</fpage><lpage>835</lpage><pub-id pub-id-type="pmid">25162889</pub-id></element-citation></ref><ref id="bib59"><label>59</label><element-citation publication-type="journal" id="sbref590"><person-group person-group-type="author"><name><surname>Zhao</surname><given-names>J</given-names></name><name><surname>Alshukairi</surname><given-names>AN</given-names></name><name><surname>Baharoon</surname><given-names>SA</given-names></name></person-group><article-title>Recovery from the Middle East respiratory syndrome is associated with antibody and T-cell responses</article-title><source>Sci Immunol</source><volume>2</volume><year>2017</year><object-id pub-id-type="publisher-id">eaan5393</object-id></element-citation></ref><ref id="bib60"><label>60</label><element-citation publication-type="journal" id="sbref600"><person-group person-group-type="author"><name><surname>Alshukairi</surname><given-names>AN</given-names></name><name><surname>Khalid</surname><given-names>I</given-names></name><name><surname>Ahmed</surname><given-names>WA</given-names></name></person-group><article-title>Antibody response and disease severity in healthcare worker MERS survivors</article-title><source>Emerg Infect Dis</source><volume>22</volume><year>2016</year><fpage>1113</fpage><lpage>1115</lpage></element-citation></ref><ref id="bib61"><label>61</label><element-citation publication-type="journal" id="sbref610"><person-group person-group-type="author"><name><surname>Arabi</surname><given-names>YM</given-names></name><name><surname>Balkhy</surname><given-names>HH</given-names></name><name><surname>Hayden</surname><given-names>FG</given-names></name></person-group><article-title>Middle East respiratory syndrome</article-title><source>N Engl J Med</source><volume>376</volume><year>2017</year><fpage>584</fpage><lpage>594</lpage><pub-id pub-id-type="pmid">28177862</pub-id></element-citation></ref><ref id="bib62"><label>62</label><element-citation publication-type="journal" id="sbref620"><person-group person-group-type="author"><name><surname>Cauchemez</surname><given-names>S</given-names></name><name><surname>Fraser</surname><given-names>C</given-names></name><name><surname>Van Kerkhove</surname><given-names>MD</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus: quantification of the extent of the epidemic, surveillance biases, and transmissibility</article-title><source>Lancet Infect Dis</source><volume>14</volume><year>2014</year><fpage>50</fpage><lpage>56</lpage><pub-id pub-id-type="pmid">24239323</pub-id></element-citation></ref><ref id="bib63"><label>63</label><element-citation publication-type="journal" id="sbref630"><person-group person-group-type="author"><name><surname>Breban</surname><given-names>R</given-names></name><name><surname>Riou</surname><given-names>J</given-names></name><name><surname>Fontanet</surname><given-names>A</given-names></name></person-group><article-title>Interhuman transmissibility of Middle East respiratory syndrome coronavirus: estimation of pandemic risk</article-title><source>Lancet</source><volume>382</volume><year>2013</year><fpage>694</fpage><lpage>699</lpage><pub-id pub-id-type="pmid">23831141</pub-id></element-citation></ref><ref id="bib64"><label>64</label><element-citation publication-type="journal" id="sbref640"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>SH</given-names></name><name><surname>Ko</surname><given-names>JH</given-names></name><name><surname>Park</surname><given-names>GE</given-names></name></person-group><article-title>Atypical presentations of MERS-CoV infection in immunocompromised hosts</article-title><source>J Infect Chemother</source><volume>23</volume><year>2017</year><fpage>769</fpage><lpage>773</lpage><pub-id pub-id-type="pmid">28545936</pub-id></element-citation></ref><ref id="bib65"><label>65</label><element-citation publication-type="journal" id="sbref650"><person-group person-group-type="author"><name><surname>Drosten</surname><given-names>C</given-names></name><name><surname>Seilmaier</surname><given-names>M</given-names></name><name><surname>Corman</surname><given-names>VM</given-names></name></person-group><article-title>Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection</article-title><source>Lancet Infect Dis</source><volume>13</volume><year>2013</year><fpage>745</fpage><lpage>751</lpage><pub-id pub-id-type="pmid">23782859</pub-id></element-citation></ref><ref id="bib66"><label>66</label><element-citation publication-type="journal" id="sbref660"><person-group person-group-type="author"><name><surname>Grant</surname><given-names>R</given-names></name><name><surname>Malik</surname><given-names>MR</given-names></name><name><surname>Elkholy</surname><given-names>A</given-names></name><name><surname>Van Kerkhove</surname><given-names>MD</given-names></name></person-group><article-title>A review of asymptomatic and sub-clinical Middle East respiratory syndrome coronavirus infections</article-title><source>Epidemiol Rev</source><year>2019</year><comment>published online Nov 29.</comment><pub-id pub-id-type="doi">10.1093/epirev/mxz009</pub-id></element-citation></ref><ref id="bib67"><label>67</label><element-citation publication-type="journal" id="sbref670"><person-group person-group-type="author"><collab>WHO MERS-CoV Research Group</collab></person-group><article-title>State of knowledge and data gaps of Middle East respiratory syndrome coronavirus (MERS-CoV) in humans</article-title><source>PLoS Curr</source><volume>5</volume><year>2013</year></element-citation></ref><ref id="bib68"><label>68</label><element-citation publication-type="journal" id="sbref680"><person-group person-group-type="author"><name><surname>Kim</surname><given-names>JE</given-names></name><name><surname>Heo</surname><given-names>JH</given-names></name><name><surname>Kim</surname><given-names>HO</given-names></name></person-group><article-title>Neurological complications during treatment of Middle East respiratory syndrome</article-title><source>J Clin Neurol</source><volume>13</volume><year>2017</year><fpage>227</fpage><lpage>233</lpage><pub-id pub-id-type="pmid">28748673</pub-id></element-citation></ref><ref id="bib69"><label>69</label><element-citation publication-type="journal" id="sbref690"><person-group person-group-type="author"><name><surname>Alfaraj</surname><given-names>SH</given-names></name><name><surname>Al-Tawfiq</surname><given-names>JA</given-names></name><name><surname>Altuwaijri</surname><given-names>TA</given-names></name><name><surname>Alanazi</surname><given-names>M</given-names></name><name><surname>Alzahrani</surname><given-names>N</given-names></name><name><surname>Memish</surname><given-names>ZA</given-names></name></person-group><article-title>Middle east respiratory syndrome coronavirus transmission among health care workers: implication for infection control</article-title><source>Am J Infect Control</source><volume>46</volume><year>2018</year><fpage>165</fpage><lpage>168</lpage><pub-id pub-id-type="pmid">28958446</pub-id></element-citation></ref><ref id="bib70"><label>70</label><element-citation publication-type="journal" id="sbref700"><person-group person-group-type="author"><name><surname>Hui</surname><given-names>DS</given-names></name><name><surname>Memish</surname><given-names>ZA</given-names></name><name><surname>Zumla</surname><given-names>A</given-names></name></person-group><article-title>Severe acute respiratory syndrome vs the Middle East respiratory syndrome</article-title><source>Curr Opin Pulm Med</source><volume>20</volume><year>2014</year><fpage>233</fpage><lpage>241</lpage><pub-id pub-id-type="pmid">24626235</pub-id></element-citation></ref><ref id="bib71"><label>71</label><element-citation publication-type="journal" id="sbref710"><person-group person-group-type="author"><name><surname>Al-Tawfiq</surname><given-names>JA</given-names></name><name><surname>Kattan</surname><given-names>RF</given-names></name><name><surname>Memish</surname><given-names>ZA</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus disease is rare in children: an update from Saudi Arabia</article-title><source>World J Clin Pediatr</source><volume>5</volume><year>2016</year><fpage>391</fpage><lpage>396</lpage><pub-id pub-id-type="pmid">27872828</pub-id></element-citation></ref><ref id="bib72"><label>72</label><element-citation publication-type="journal" id="sbref720"><person-group person-group-type="author"><name><surname>Alfaraj</surname><given-names>SH</given-names></name><name><surname>Al-Tawfiq</surname><given-names>JA</given-names></name><name><surname>Altuwaijri</surname><given-names>TA</given-names></name><name><surname>Memish</surname><given-names>ZA</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus in pediatrics: a report of seven cases from Saudi Arabia</article-title><source>Front Med</source><volume>13</volume><year>2019</year><fpage>126</fpage><lpage>130</lpage><pub-id pub-id-type="pmid">29623560</pub-id></element-citation></ref><ref id="bib73"><label>73</label><element-citation publication-type="journal" id="sbref730"><person-group person-group-type="author"><name><surname>Memish</surname><given-names>ZA</given-names></name><name><surname>Al-Tawfiq</surname><given-names>JA</given-names></name><name><surname>Assiri</surname><given-names>A</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus disease in children</article-title><source>Pediatr Infect Dis J</source><volume>33</volume><year>2014</year><fpage>904</fpage><lpage>906</lpage><pub-id pub-id-type="pmid">24763193</pub-id></element-citation></ref><ref id="bib74"><label>74</label><element-citation publication-type="journal" id="sbref740"><person-group person-group-type="author"><name><surname>Mobaraki</surname><given-names>K</given-names></name><name><surname>Ahmadzadeh</surname><given-names>J</given-names></name></person-group><article-title>Current epidemiological status of Middle East respiratory syndrome coronavirus in the world from 1.1.2017 to 17.1.2018: a cross-sectional study</article-title><source>BMC Infect Dis</source><volume>19</volume><year>2019</year><fpage>351</fpage><pub-id pub-id-type="pmid">31029095</pub-id></element-citation></ref><ref id="bib75"><label>75</label><element-citation publication-type="journal" id="sbref750"><person-group person-group-type="author"><name><surname>Alfaraj</surname><given-names>SH</given-names></name><name><surname>Al-Tawfiq</surname><given-names>JA</given-names></name><name><surname>Memish</surname><given-names>ZA</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus (MERS-CoV) infection during pregnancy: report of two cases & review of the literature</article-title><source>J Microbiol Immunol Infect</source><volume>52</volume><year>2019</year><fpage>501</fpage><lpage>503</lpage><pub-id pub-id-type="pmid">29907538</pub-id></element-citation></ref><ref id="bib76"><label>76</label><element-citation publication-type="other" id="sbref760"><person-group person-group-type="author"><collab>WHO</collab></person-group><article-title>Infection prevention and control during health care for probable or confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection</article-title><ext-link ext-link-type="uri" xlink:href="https://www.who.int/csr/disease/coronavirus_infections/ipc-mers-cov/en/" id="interrefs120">https://www.who.int/csr/disease/coronavirus_infections/ipc-mers-cov/en/</ext-link><year>2015</year></element-citation></ref><ref id="bib77"><label>77</label><element-citation publication-type="other" id="sbref770"><person-group person-group-type="author"><collab>WHO</collab></person-group><article-title>Laboratory testing for middle east respiratory syndrome coronavirus</article-title><ext-link ext-link-type="uri" xlink:href="https://apps.who.int/iris/bitstream/handle/10665/259952/WHO-MERS-LAB-15.1-Rev1-2018-eng.pdf?sequence=1" id="interrefs130">https://apps.who.int/iris/bitstream/handle/10665/259952/WHO-MERS-LAB-15.1-Rev1-2018-eng.pdf?sequence=1</ext-link><year>2018</year></element-citation></ref><ref id="bib78"><label>78</label><element-citation publication-type="other" id="sbref780"><person-group person-group-type="author"><collab>CDC</collab></person-group><article-title>CDC laboratory testing for Middle East respiratory syndrome coronavirus (MERS-CoV)</article-title><ext-link ext-link-type="uri" xlink:href="https://www.cdc.gov/coronavirus/mers/lab/lab-testing.html" id="interrefs140">https://www.cdc.gov/coronavirus/mers/lab/lab-testing.html</ext-link></element-citation></ref><ref id="bib79"><label>79</label><element-citation publication-type="journal" id="sbref790"><person-group person-group-type="author"><name><surname>Memish</surname><given-names>ZA</given-names></name><name><surname>Al-Tawfiq</surname><given-names>JA</given-names></name><name><surname>Makhdoom</surname><given-names>HQ</given-names></name></person-group><article-title>Respiratory tract samples, viral load, and genome fraction yield in patients with Middle East respiratory syndrome</article-title><source>J Infect Dis</source><volume>210</volume><year>2014</year><fpage>1590</fpage><lpage>1594</lpage><pub-id pub-id-type="pmid">24837403</pub-id></element-citation></ref><ref id="bib80"><label>80</label><element-citation publication-type="journal" id="sbref800"><person-group person-group-type="author"><name><surname>Oh</surname><given-names>MD</given-names></name><name><surname>Park</surname><given-names>WB</given-names></name><name><surname>Choe</surname><given-names>PG</given-names></name></person-group><article-title>Viral load kinetics of MERS coronavirus infection</article-title><source>N Engl J Med</source><volume>375</volume><year>2016</year><fpage>1303</fpage><lpage>1305</lpage></element-citation></ref><ref id="bib81"><label>81</label><element-citation publication-type="journal" id="sbref810"><person-group person-group-type="author"><name><surname>Bermingham</surname><given-names>A</given-names></name><name><surname>Chand</surname><given-names>MA</given-names></name><name><surname>Brown</surname><given-names>CS</given-names></name></person-group><article-title>Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United Kingdom from the Middle East, September 2012</article-title><source>Euro Surveill</source><volume>17</volume><year>2012</year><object-id pub-id-type="publisher-id">20290</object-id></element-citation></ref><ref id="bib82"><label>82</label><element-citation publication-type="journal" id="sbref820"><person-group person-group-type="author"><name><surname>Alfaraj</surname><given-names>SH</given-names></name><name><surname>Al-Tawfiq</surname><given-names>JA</given-names></name><name><surname>Memish</surname><given-names>ZA</given-names></name></person-group><article-title>Middle east respiratory syndrome coronavirus intermittent positive cases: implications for infection control</article-title><source>Am J Infect Control</source><volume>47</volume><year>2019</year><fpage>290</fpage><lpage>293</lpage><pub-id pub-id-type="pmid">30352694</pub-id></element-citation></ref><ref id="bib83"><label>83</label><element-citation publication-type="other" id="sbref830"><person-group person-group-type="author"><collab>WHO</collab></person-group><article-title>Laboratory biorisk management for laboratories handling human specimens suspected of confirmed to contain novel coronavirus: interim recommendations</article-title><ext-link ext-link-type="uri" xlink:href="https://www.who.int/csr/disease/coronavirus_infections/Biosafety_InterimRecommendations_NovelCoronavirus_19Feb13.pdf?ua=1" id="interrefs150">https://www.who.int/csr/disease/coronavirus_infections/Biosafety_InterimRecommendations_NovelCoronavirus_19Feb13.pdf?ua=1</ext-link><year>2013</year></element-citation></ref><ref id="bib84"><label>84</label><element-citation publication-type="journal" id="sbref840"><person-group person-group-type="author"><name><surname>Kelly-Cirino</surname><given-names>C</given-names></name><name><surname>Mazzola</surname><given-names>LT</given-names></name><name><surname>Chua</surname><given-names>A</given-names></name><name><surname>Oxenford</surname><given-names>CJ</given-names></name><name><surname>Van Kerkhove</surname><given-names>MD</given-names></name></person-group><article-title>An updated roadmap for MERS-CoV research and product development: focus on diagnostics</article-title><source>BMJ Glob Health</source><volume>4</volume><year>2019</year><object-id pub-id-type="publisher-id">e001105</object-id></element-citation></ref><ref id="bib85"><label>85</label><element-citation publication-type="journal" id="sbref850"><person-group person-group-type="author"><name><surname>Frans</surname><given-names>G</given-names></name><name><surname>Beuselinck</surname><given-names>K</given-names></name><name><surname>Peeters</surname><given-names>B</given-names></name></person-group><article-title>Migrating a lab-developed MERS-CoV real-time PCR to 3 “sample to result” systems: experiences on optimization and validation</article-title><source>Diagn Microbiol Infect Dis</source><volume>94</volume><year>2019</year><fpage>349</fpage><lpage>354</lpage><pub-id pub-id-type="pmid">30929995</pub-id></element-citation></ref><ref id="bib86"><label>86</label><element-citation publication-type="journal" id="sbref860"><person-group person-group-type="author"><name><surname>Huang</surname><given-names>P</given-names></name><name><surname>Wang</surname><given-names>H</given-names></name><name><surname>Cao</surname><given-names>Z</given-names></name></person-group><article-title>A rapid and specific assay for the detection of MERS-CoV</article-title><source>Front Microbiol</source><volume>9</volume><year>2018</year><object-id pub-id-type="publisher-id">1101</object-id></element-citation></ref><ref id="bib87"><label>87</label><element-citation publication-type="journal" id="sbref870"><person-group person-group-type="author"><name><surname>Hashem</surname><given-names>AM</given-names></name><name><surname>Al-Amri</surname><given-names>SS</given-names></name><name><surname>Al-Subhi</surname><given-names>TL</given-names></name></person-group><article-title>Development and validation of different indirect ELISAS for MERS-CoV serological testing</article-title><source>J Immunol Methods</source><volume>466</volume><year>2019</year><fpage>41</fpage><lpage>46</lpage><pub-id pub-id-type="pmid">30659836</pub-id></element-citation></ref><ref id="bib88"><label>88</label><element-citation publication-type="journal" id="sbref880"><person-group person-group-type="author"><name><surname>Park</surname><given-names>SW</given-names></name><name><surname>Perera</surname><given-names>RA</given-names></name><name><surname>Choe</surname><given-names>PG</given-names></name></person-group><article-title>Comparison of serological assays in human Middle East respiratory syndrome (MERS)-coronavirus infection</article-title><source>Euro Surveill</source><volume>20</volume><year>2015</year><fpage>1</fpage><lpage>5</lpage><pub-id pub-id-type="pmid">26132766</pub-id></element-citation></ref><ref id="bib89"><label>89</label><element-citation publication-type="journal" id="sbref890"><person-group person-group-type="author"><name><surname>Perera</surname><given-names>RA</given-names></name><name><surname>Wang</surname><given-names>P</given-names></name><name><surname>Gomaa</surname><given-names>MR</given-names></name></person-group><article-title>Seroepidemiology for MERS coronavirus using microneutralisation and pseudoparticle virus neutralisation assays reveal a high prevalence of antibody in Dromedary camels in Egypt, June 2013</article-title><source>Euro Surveill</source><volume>18</volume><year>2013</year><object-id pub-id-type="publisher-id">20574</object-id></element-citation></ref><ref id="bib90"><label>90</label><element-citation publication-type="journal" id="sbref900"><person-group person-group-type="author"><name><surname>Okba</surname><given-names>NMA</given-names></name><name><surname>Raj</surname><given-names>VS</given-names></name><name><surname>Widjaja</surname><given-names>I</given-names></name></person-group><article-title>Sensitive and specific detection of low-level antibody responses in mild Middle East respiratory syndrome coronavirus infections</article-title><source>Emerg Infect Dis</source><volume>25</volume><year>2019</year><fpage>1868</fpage><lpage>1877</lpage><pub-id pub-id-type="pmid">31423970</pub-id></element-citation></ref><ref id="bib91"><label>91</label><element-citation publication-type="journal" id="sbref910"><person-group person-group-type="author"><name><surname>Das</surname><given-names>KM</given-names></name><name><surname>Lee</surname><given-names>EY</given-names></name><name><surname>Al Jawder</surname><given-names>SE</given-names></name></person-group><article-title>Acute Middle East respiratory syndrome coronavirus: temporal lung changes observed on the chest radiographs of 55 patients</article-title><source>AJR Am J Roentgenol</source><volume>205</volume><year>2015</year><fpage>W267</fpage><lpage>W274</lpage><pub-id pub-id-type="pmid">26102309</pub-id></element-citation></ref><ref id="bib92"><label>92</label><element-citation publication-type="journal" id="sbref920"><person-group person-group-type="author"><name><surname>Das</surname><given-names>KM</given-names></name><name><surname>Lee</surname><given-names>EY</given-names></name><name><surname>Langer</surname><given-names>RD</given-names></name><name><surname>Larsson</surname><given-names>SG</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus: what does a radiologist need to know?</article-title><source>AJR Am J Roentgenol</source><volume>206</volume><year>2016</year><fpage>1193</fpage><lpage>1201</lpage><pub-id pub-id-type="pmid">26998804</pub-id></element-citation></ref><ref id="bib93"><label>93</label><element-citation publication-type="journal" id="sbref930"><person-group person-group-type="author"><name><surname>Ajlan</surname><given-names>AM</given-names></name><name><surname>Ahyad</surname><given-names>RA</given-names></name><name><surname>Jamjoom</surname><given-names>LG</given-names></name><name><surname>Alharthy</surname><given-names>A</given-names></name><name><surname>Madani</surname><given-names>TA</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus (MERS-CoV) infection: chest CT findings</article-title><source>AJR Am J Roentgenol</source><volume>203</volume><year>2014</year><fpage>782</fpage><lpage>787</lpage><pub-id pub-id-type="pmid">24918624</pub-id></element-citation></ref><ref id="bib94"><label>94</label><element-citation publication-type="journal" id="sbref940"><person-group person-group-type="author"><name><surname>Das</surname><given-names>KM</given-names></name><name><surname>Lee</surname><given-names>EY</given-names></name><name><surname>Enani</surname><given-names>MA</given-names></name></person-group><article-title>CT correlation with outcomes in 15 patients with acute Middle East respiratory syndrome coronavirus</article-title><source>AJR Am J Roentgenol</source><volume>204</volume><year>2015</year><fpage>736</fpage><lpage>742</lpage><pub-id pub-id-type="pmid">25615627</pub-id></element-citation></ref><ref id="bib95"><label>95</label><element-citation publication-type="journal" id="sbref950"><person-group person-group-type="author"><name><surname>Das</surname><given-names>KM</given-names></name><name><surname>Lee</surname><given-names>EY</given-names></name><name><surname>Singh</surname><given-names>R</given-names></name></person-group><article-title>Follow-up chest radiographic findings in patients with MERS-CoV after recovery</article-title><source>Indian J Radiol Imaging</source><volume>27</volume><year>2017</year><fpage>342</fpage><lpage>349</lpage><pub-id pub-id-type="pmid">29089687</pub-id></element-citation></ref><ref id="bib96"><label>96</label><element-citation publication-type="other" id="sbref960"><person-group person-group-type="author"><collab>WHO</collab></person-group><article-title>Home care for patients with Middle East respiratory syndrome coronavirus (MERS-CoV) infection presenting with mild symptoms and management of contacts interim guidance</article-title><ext-link ext-link-type="uri" xlink:href="https://apps.who.int/iris/bitstream/handle/10665/272948/WHO-MERS-IPC-18.1-eng.pdf?ua=1" id="interrefs160">https://apps.who.int/iris/bitstream/handle/10665/272948/WHO-MERS-IPC-18.1-eng.pdf?ua=1</ext-link><year>June 2018</year></element-citation></ref><ref id="bib97"><label>97</label><element-citation publication-type="journal" id="sbref970"><person-group person-group-type="author"><name><surname>Momattin</surname><given-names>H</given-names></name><name><surname>Al-Ali</surname><given-names>AY</given-names></name><name><surname>Al-Tawfiq</surname><given-names>JA</given-names></name></person-group><article-title>A systematic review of therapeutic agents for the treatment of the Middle East respiratory syndrome coronavirus (MERS-CoV)</article-title><source>Travel Med Infect Dis</source><volume>30</volume><year>2019</year><fpage>9</fpage><lpage>18</lpage><pub-id pub-id-type="pmid">31252170</pub-id></element-citation></ref><ref id="bib98"><label>98</label><element-citation publication-type="journal" id="sbref980"><person-group person-group-type="author"><name><surname>Arabi</surname><given-names>Y</given-names></name><name><surname>Balkhy</surname><given-names>H</given-names></name><name><surname>Hajeer</surname><given-names>AH</given-names></name></person-group><article-title>Feasibility, safety, clinical, and laboratory effects of convalescent plasma therapy for patients with Middle East respiratory syndrome coronavirus infection: a study protocol</article-title><source>Springerplus</source><volume>4</volume><year>2015</year><fpage>709</fpage><pub-id pub-id-type="pmid">26618098</pub-id></element-citation></ref><ref id="bib99"><label>99</label><element-citation publication-type="journal" id="sbref990"><person-group person-group-type="author"><name><surname>Arabi</surname><given-names>YM</given-names></name><name><surname>Alothman</surname><given-names>A</given-names></name><name><surname>Balkhy</surname><given-names>HH</given-names></name></person-group><article-title>Treatment of Middle East respiratory syndrome with a combination of lopinavir-ritonavir and interferon-beta1b (MIRACLE trial): study protocol for a randomized controlled trial</article-title><source>Trials</source><volume>19</volume><year>2018</year><fpage>81</fpage><pub-id pub-id-type="pmid">29382391</pub-id></element-citation></ref><ref id="bib100"><label>100</label><element-citation publication-type="journal" id="sbref1000"><person-group person-group-type="author"><name><surname>Arabi</surname><given-names>YM</given-names></name><name><surname>Mandourah</surname><given-names>Y</given-names></name><name><surname>Al-Hameed</surname><given-names>F</given-names></name></person-group><article-title>Corticosteroid therapy for critically ill patients with Middle East respiratory syndrome</article-title><source>Am J Respir Crit Care Med</source><volume>197</volume><year>2018</year><fpage>757</fpage><lpage>767</lpage><pub-id pub-id-type="pmid">29161116</pub-id></element-citation></ref><ref id="bib101"><label>101</label><element-citation publication-type="journal" id="sbref1010"><person-group person-group-type="author"><name><surname>Behzadi</surname><given-names>MA</given-names></name><name><surname>Leyva-Grado</surname><given-names>VH</given-names></name></person-group><article-title>Overview of current therapeutics and novel candidates against influenza, respiratory syncytial virus, and Middle East respiratory syndrome coronavirus infections</article-title><source>Front Microbiol</source><volume>10</volume><year>2019</year><object-id pub-id-type="publisher-id">1327</object-id></element-citation></ref><ref id="bib102"><label>102</label><element-citation publication-type="journal" id="sbref1020"><person-group person-group-type="author"><name><surname>Beigel</surname><given-names>JH</given-names></name><name><surname>Nam</surname><given-names>HH</given-names></name><name><surname>Adams</surname><given-names>PL</given-names></name></person-group><article-title>Advances in respiratory virus therapeutics—a meeting report from the 6th ISIRV antiviral group conference</article-title><source>Antiviral Res</source><volume>167</volume><year>2019</year><fpage>45</fpage><lpage>67</lpage><pub-id pub-id-type="pmid">30974127</pub-id></element-citation></ref><ref id="bib103"><label>103</label><element-citation publication-type="journal" id="sbref1030"><person-group person-group-type="author"><name><surname>Rabaan</surname><given-names>AA</given-names></name><name><surname>Alahmed</surname><given-names>SH</given-names></name><name><surname>Bazzi</surname><given-names>AM</given-names></name><name><surname>Alhani</surname><given-names>HM</given-names></name></person-group><article-title>A review of candidate therapies for Middle East respiratory syndrome from a molecular perspective</article-title><source>J Med Microbiol</source><volume>66</volume><year>2017</year><fpage>1261</fpage><lpage>1274</lpage><pub-id pub-id-type="pmid">28855003</pub-id></element-citation></ref><ref id="bib104"><label>104</label><element-citation publication-type="journal" id="sbref1040"><person-group person-group-type="author"><name><surname>Zhou</surname><given-names>Y</given-names></name><name><surname>Yang</surname><given-names>Y</given-names></name><name><surname>Huang</surname><given-names>J</given-names></name><name><surname>Jiang</surname><given-names>S</given-names></name><name><surname>Du</surname><given-names>L</given-names></name></person-group><article-title>Advances in MERS-CoV vaccines and therapeutics based on the receptor-binding domain</article-title><source>Viruses</source><volume>11</volume><year>2019</year><fpage>60</fpage></element-citation></ref><ref id="bib105"><label>105</label><element-citation publication-type="journal" id="sbref1050"><person-group person-group-type="author"><name><surname>Zumla</surname><given-names>A</given-names></name><name><surname>Chan</surname><given-names>JF</given-names></name><name><surname>Azhar</surname><given-names>EI</given-names></name><name><surname>Hui</surname><given-names>DS</given-names></name><name><surname>Yuen</surname><given-names>KY</given-names></name></person-group><article-title>Coronaviruses—drug discovery and therapeutic options</article-title><source>Nat Rev Drug Discov</source><volume>15</volume><year>2016</year><fpage>327</fpage><lpage>347</lpage><pub-id pub-id-type="pmid">26868298</pub-id></element-citation></ref><ref id="bib106"><label>106</label><element-citation publication-type="journal" id="sbref1060"><person-group person-group-type="author"><name><surname>Zhao</surname><given-names>J</given-names></name><name><surname>Perera</surname><given-names>RA</given-names></name><name><surname>Kayali</surname><given-names>G</given-names></name><name><surname>Meyerholz</surname><given-names>D</given-names></name><name><surname>Perlman</surname><given-names>S</given-names></name><name><surname>Peiris</surname><given-names>M</given-names></name></person-group><article-title>Passive immunotherapy with dromedary immune serum in an experimental animal model for Middle East respiratory syndrome coronavirus infection</article-title><source>J Virol</source><volume>89</volume><year>2015</year><fpage>6117</fpage><lpage>6120</lpage><pub-id pub-id-type="pmid">25787284</pub-id></element-citation></ref><ref id="bib107"><label>107</label><element-citation publication-type="journal" id="sbref1070"><person-group person-group-type="author"><name><surname>Ko</surname><given-names>JH</given-names></name><name><surname>Seok</surname><given-names>H</given-names></name><name><surname>Cho</surname><given-names>SY</given-names></name></person-group><article-title>Challenges of convalescent plasma infusion therapy in Middle East respiratory coronavirus infection: a single centre experience</article-title><source>Antivir Ther</source><volume>23</volume><year>2018</year><fpage>617</fpage><lpage>622</lpage><pub-id pub-id-type="pmid">29923831</pub-id></element-citation></ref><ref id="bib108"><label>108</label><element-citation publication-type="journal" id="sbref1080"><person-group person-group-type="author"><name><surname>Arabi</surname><given-names>YM</given-names></name><name><surname>Deeb</surname><given-names>AM</given-names></name><name><surname>Al-Hameed</surname><given-names>F</given-names></name></person-group><article-title>Macrolides in critically ill patients with Middle East respiratory syndrome</article-title><source>Int J Infect Dis</source><volume>81</volume><year>2019</year><fpage>184</fpage><lpage>190</lpage><pub-id pub-id-type="pmid">30690213</pub-id></element-citation></ref><ref id="bib109"><label>109</label><element-citation publication-type="journal" id="sbref1090"><person-group person-group-type="author"><name><surname>Alraddadi</surname><given-names>BM</given-names></name><name><surname>Qushmaq</surname><given-names>I</given-names></name><name><surname>Al-Hameed</surname><given-names>FM</given-names></name></person-group><article-title>Noninvasive ventilation in critically ill patients with the Middle East respiratory syndrome</article-title><source>Influenza Other Respir Viruses</source><volume>13</volume><year>2019</year><fpage>382</fpage><lpage>390</lpage><pub-id pub-id-type="pmid">30884185</pub-id></element-citation></ref><ref id="bib110"><label>110</label><element-citation publication-type="journal" id="sbref1100"><person-group person-group-type="author"><name><surname>Stalin Raj</surname><given-names>V</given-names></name><name><surname>Okba</surname><given-names>NMA</given-names></name><name><surname>Gutierrez-Alvarez</surname><given-names>J</given-names></name></person-group><article-title>Chimeric camel/human heavy-chain antibodies protect against MERS-CoV infection</article-title><source>Sci Adv</source><volume>4</volume><year>2018</year><object-id pub-id-type="publisher-id">eaas9667</object-id></element-citation></ref><ref id="bib111"><label>111</label><element-citation publication-type="journal" id="sbref1110"><person-group person-group-type="author"><name><surname>Wang</surname><given-names>L</given-names></name><name><surname>Shi</surname><given-names>W</given-names></name><name><surname>Chappell</surname><given-names>JD</given-names></name></person-group><article-title>Importance of neutralizing monoclonal antibodies targeting multiple antigenic sites on the Middle East respiratory syndrome coronavirus spike glycoprotein to avoid neutralization escape</article-title><source>J Virol</source><volume>92</volume><year>2018</year><fpage>e02002</fpage><lpage>e02017</lpage><pub-id pub-id-type="pmid">29514901</pub-id></element-citation></ref><ref id="bib112"><label>112</label><element-citation publication-type="journal" id="sbref1120"><person-group person-group-type="author"><name><surname>Widjaja</surname><given-names>I</given-names></name><name><surname>Wang</surname><given-names>C</given-names></name><name><surname>van Haperen</surname><given-names>R</given-names></name></person-group><article-title>Towards a solution to MERS: protective human monoclonal antibodies targeting different domains and functions of the MERS-coronavirus spike glycoprotein</article-title><source>Emerg Microbes Infect</source><volume>8</volume><year>2019</year><fpage>516</fpage><lpage>530</lpage><pub-id pub-id-type="pmid">30938227</pub-id></element-citation></ref><ref id="bib113"><label>113</label><element-citation publication-type="journal" id="sbref1130"><person-group person-group-type="author"><name><surname>Lee</surname><given-names>SM</given-names></name><name><surname>Kang</surname><given-names>WS</given-names></name><name><surname>Cho</surname><given-names>AR</given-names></name><name><surname>Kim</surname><given-names>T</given-names></name><name><surname>Park</surname><given-names>JK</given-names></name></person-group><article-title>Psychological impact of the 2015 MERS outbreak on hospital workers and quarantined hemodialysis patients</article-title><source>Compr Psychiatry</source><volume>87</volume><year>2018</year><fpage>123</fpage><lpage>127</lpage><pub-id pub-id-type="pmid">30343247</pub-id></element-citation></ref><ref id="bib114"><label>114</label><element-citation publication-type="journal" id="sbref1140"><person-group person-group-type="author"><name><surname>Ahmed</surname><given-names>AE</given-names></name></person-group><article-title>The predictors of 3- and 30-day mortality in 660 MERS-CoV patients</article-title><source>BMC Infect Dis</source><volume>17</volume><year>2017</year><fpage>615</fpage><pub-id pub-id-type="pmid">28893197</pub-id></element-citation></ref><ref id="bib115"><label>115</label><element-citation publication-type="journal" id="sbref1150"><person-group person-group-type="author"><name><surname>Park</surname><given-names>JE</given-names></name><name><surname>Jung</surname><given-names>S</given-names></name><name><surname>Kim</surname><given-names>A</given-names></name><name><surname>Park</surname><given-names>JE</given-names></name></person-group><article-title>MERS transmission and risk factors: a systematic review</article-title><source>BMC Public Health</source><volume>18</volume><year>2018</year><fpage>574</fpage><pub-id pub-id-type="pmid">29716568</pub-id></element-citation></ref><ref id="bib116"><label>116</label><element-citation publication-type="journal" id="sbref1160"><person-group person-group-type="author"><name><surname>Rahman</surname><given-names>A</given-names></name><name><surname>Sarkar</surname><given-names>A</given-names></name></person-group><article-title>Risk factors for fatal Middle East respiratory syndrome coronavirus infections in Saudi Arabia: analysis of the WHO line list, 2013–2018</article-title><source>Am J Public Health</source><volume>109</volume><year>2019</year><fpage>1288</fpage><lpage>1293</lpage><pub-id pub-id-type="pmid">31318592</pub-id></element-citation></ref><ref id="bib117"><label>117</label><element-citation publication-type="journal" id="sbref1170"><person-group person-group-type="author"><name><surname>Sha</surname><given-names>J</given-names></name><name><surname>Li</surname><given-names>Y</given-names></name><name><surname>Chen</surname><given-names>X</given-names></name></person-group><article-title>Fatality risks for nosocomial outbreaks of Middle East respiratory syndrome coronavirus in the Middle East and South Korea</article-title><source>Arch Virol</source><volume>162</volume><year>2017</year><fpage>33</fpage><lpage>44</lpage><pub-id pub-id-type="pmid">27664026</pub-id></element-citation></ref><ref id="bib118"><label>118</label><element-citation publication-type="journal" id="sbref1180"><person-group person-group-type="author"><name><surname>Seys</surname><given-names>LJM</given-names></name><name><surname>Widagdo</surname><given-names>W</given-names></name><name><surname>Verhamme</surname><given-names>FM</given-names></name></person-group><article-title>DPP4, the Middle East respiratory syndrome coronavirus receptor, is upregulated in lungs of smokers and chronic obstructive pulmonary disease patients</article-title><source>Clin Infect Dis</source><volume>66</volume><year>2018</year><fpage>45</fpage><lpage>53</lpage><pub-id pub-id-type="pmid">29020176</pub-id></element-citation></ref><ref id="bib119"><label>119</label><element-citation publication-type="journal" id="sbref1190"><person-group person-group-type="author"><name><surname>Batawi</surname><given-names>S</given-names></name><name><surname>Tarazan</surname><given-names>N</given-names></name><name><surname>Al-Raddadi</surname><given-names>R</given-names></name></person-group><article-title>Quality of life reported by survivors after hospitalization for Middle East respiratory syndrome (MERS)</article-title><source>Health Qual Life Outcomes</source><volume>17</volume><year>2019</year><fpage>101</fpage><pub-id pub-id-type="pmid">31186042</pub-id></element-citation></ref><ref id="bib120"><label>120</label><element-citation publication-type="journal" id="sbref1200"><person-group person-group-type="author"><name><surname>Ngai</surname><given-names>JC</given-names></name><name><surname>Ko</surname><given-names>FW</given-names></name><name><surname>Ng</surname><given-names>SS</given-names></name><name><surname>To</surname><given-names>KW</given-names></name><name><surname>Tong</surname><given-names>M</given-names></name><name><surname>Hui</surname><given-names>DS</given-names></name></person-group><article-title>The long-term impact of severe acute respiratory syndrome on pulmonary function, exercise capacity and health status</article-title><source>Respirology</source><volume>15</volume><year>2010</year><fpage>543</fpage><lpage>550</lpage><pub-id pub-id-type="pmid">20337995</pub-id></element-citation></ref><ref id="bib121"><label>121</label><element-citation publication-type="other" id="sbref1210"><person-group person-group-type="author"><collab>WHO</collab></person-group><article-title>WHO target product profiles for MERS-CoV vaccines</article-title><ext-link ext-link-type="uri" xlink:href="https://www.who.int/blueprint/what/research-development/MERS_CoV_TPP_15052017.pdf?ua=1&ua=1" id="interrefs170">https://www.who.int/blueprint/what/research-development/MERS_CoV_TPP_15052017.pdf?ua=1&ua=1</ext-link><year>2017</year></element-citation></ref><ref id="bib122"><label>122</label><element-citation publication-type="journal" id="sbref1220"><person-group person-group-type="author"><name><surname>Schindewolf</surname><given-names>C</given-names></name><name><surname>Menachery</surname><given-names>VD</given-names></name></person-group><article-title>Middle East respiratory syndrome vaccine candidates: cautious optimism</article-title><source>Viruses</source><volume>11</volume><year>2019</year><fpage>e74</fpage><pub-id pub-id-type="pmid">30658390</pub-id></element-citation></ref><ref id="bib123"><label>123</label><element-citation publication-type="journal" id="sbref1230"><person-group person-group-type="author"><name><surname>Hemida</surname><given-names>MG</given-names></name></person-group><article-title>Middle East respiratory syndrome coronavirus and the One Health concept</article-title><source>PeerJ</source><volume>7</volume><year>2019</year><object-id pub-id-type="publisher-id">e7556</object-id></element-citation></ref><ref id="bib124"><label>124</label><element-citation publication-type="journal" id="sbref1240"><person-group person-group-type="author"><name><surname>Hemida</surname><given-names>MG</given-names></name><name><surname>Alnaeem</surname><given-names>A</given-names></name></person-group><article-title>Some one health based control strategies for the Middle East respiratory syndrome coronavirus</article-title><source>One Health</source><volume>8</volume><year>2019</year><object-id pub-id-type="publisher-id">100102</object-id></element-citation></ref><ref id="bib125"><label>125</label><element-citation publication-type="journal" id="sbref1250"><person-group person-group-type="author"><name><surname>Park</surname><given-names>S</given-names></name><name><surname>Park</surname><given-names>JY</given-names></name><name><surname>Song</surname><given-names>Y</given-names></name><name><surname>How</surname><given-names>SH</given-names></name><name><surname>Jung</surname><given-names>KS</given-names></name></person-group><article-title>Emerging respiratory infections threatening public health in the Asia-Pacific region: a position paper of the Asian Pacific society of respirology</article-title><source>Respirology</source><volume>24</volume><year>2019</year><fpage>590</fpage><lpage>597</lpage><pub-id pub-id-type="pmid">30985968</pub-id></element-citation></ref><ref id="bib126"><label>126</label><element-citation publication-type="journal" id="sbref1260"><person-group person-group-type="author"><name><surname>Zumla</surname><given-names>A</given-names></name><name><surname>Dar</surname><given-names>O</given-names></name><name><surname>Kock</surname><given-names>R</given-names></name></person-group><article-title>Taking forward a ‘one health’ approach for turning the tide against the Middle East respiratory syndrome coronavirus and other zoonotic pathogens with epidemic potential</article-title><source>Int J Infect Dis</source><volume>47</volume><year>2016</year><fpage>5</fpage><lpage>9</lpage><pub-id pub-id-type="pmid">27321961</pub-id></element-citation></ref><ref id="bib127"><label>127</label><element-citation publication-type="journal" id="sbref1270"><person-group person-group-type="author"><name><surname>Kirchdoerfer</surname><given-names>RN</given-names></name><name><surname>Ward</surname><given-names>AB</given-names></name></person-group><article-title>Structure of the SARS-CoV nsp12 polymerase bound to nsp7 and nsp8 co-factors</article-title><source>Nat Commun</source><volume>10</volume><year>2019</year><object-id pub-id-type="publisher-id">2342</object-id></element-citation></ref><ref id="bib128"><label>128</label><element-citation publication-type="journal" id="sbref1280"><person-group person-group-type="author"><name><surname>Chu</surname><given-names>DKW</given-names></name><name><surname>Hui</surname><given-names>KPY</given-names></name><name><surname>Perera</surname><given-names>R</given-names></name></person-group><article-title>MERS coronaviruses from camels in Africa exhibit region-dependent genetic diversity</article-title><source>Proc Natl Acad Sci USA</source><volume>115</volume><year>2018</year><fpage>3144</fpage><lpage>3149</lpage><pub-id pub-id-type="pmid">29507189</pub-id></element-citation></ref><ref id="bib129"><label>129</label><element-citation publication-type="journal" id="sbref1290"><person-group person-group-type="author"><name><surname>Lamers</surname><given-names>MM</given-names></name><name><surname>Raj</surname><given-names>VS</given-names></name><name><surname>Shafei</surname><given-names>M</given-names></name></person-group><article-title>Deletion variants of Middle East respiratory syndrome coronavirus from humans, Jordan, 2015</article-title><source>Emerg Infect Dis</source><volume>22</volume><year>2016</year><fpage>716</fpage><lpage>719</lpage><pub-id pub-id-type="pmid">26981770</pub-id></element-citation></ref><ref id="bib130"><label>130</label><element-citation publication-type="journal" id="sbref1300"><person-group person-group-type="author"><name><surname>Xie</surname><given-names>Q</given-names></name><name><surname>Cao</surname><given-names>Y</given-names></name><name><surname>Su</surname><given-names>J</given-names></name></person-group><article-title>Two deletion variants of Middle East respiratory syndrome coronavirus found in a patient with characteristic symptoms</article-title><source>Arch Virol</source><volume>162</volume><year>2017</year><fpage>2445</fpage><lpage>2449</lpage><pub-id pub-id-type="pmid">28421366</pub-id></element-citation></ref><ref id="bib131"><label>131</label><element-citation publication-type="journal" id="sbref1310"><person-group person-group-type="author"><name><surname>Knoops</surname><given-names>K</given-names></name><name><surname>Kikkert</surname><given-names>M</given-names></name><name><surname>Worm</surname><given-names>SH</given-names></name></person-group><article-title>SARS-coronavirus replication is supported by a reticulovesicular network of modified endoplasmic reticulum</article-title><source>PLoS Biol</source><volume>6</volume><year>2008</year><fpage>e226</fpage><pub-id pub-id-type="pmid">18798692</pub-id></element-citation></ref><ref id="bib132"><label>132</label><element-citation publication-type="journal" id="sbref1320"><person-group person-group-type="author"><name><surname>Amer</surname><given-names>H</given-names></name><name><surname>Alqahtani</surname><given-names>AS</given-names></name><name><surname>Alaklobi</surname><given-names>F</given-names></name><name><surname>Altayeb</surname><given-names>J</given-names></name><name><surname>Memish</surname><given-names>ZA</given-names></name></person-group><article-title>Healthcare worker exposure to Middle East respiratory syndrome coronavirus (MERS-CoV): revision of screening strategies urgently needed</article-title><source>Int J Infect Dis</source><volume>71</volume><year>2018</year><fpage>113</fpage><lpage>116</lpage><pub-id pub-id-type="pmid">29649550</pub-id></element-citation></ref><ref id="bib133"><label>133</label><element-citation publication-type="journal" id="sbref1330"><person-group person-group-type="author"><name><surname>Al-Abdallat</surname><given-names>MM</given-names></name><name><surname>Payne</surname><given-names>DC</given-names></name><name><surname>Alqasrawi</surname><given-names>S</given-names></name></person-group><article-title>Hospital-associated outbreak of Middle East respiratory syndrome coronavirus: a serologic, epidemiologic, and clinical description</article-title><source>Clin Infect Dis</source><volume>59</volume><year>2014</year><fpage>1225</fpage><lpage>1233</lpage><pub-id pub-id-type="pmid">24829216</pub-id></element-citation></ref><ref id="bib134"><label>134</label><element-citation publication-type="journal" id="sbref1340"><person-group person-group-type="author"><name><surname>Alenazi</surname><given-names>TH</given-names></name><name><surname>Al Arbash</surname><given-names>H</given-names></name><name><surname>El-Saed</surname><given-names>A</given-names></name></person-group><article-title>Identified transmission dynamics of Middle East respiratory syndrome coronavirus infection during an outbreak: implications of an overcrowded emergency department</article-title><source>Clin Infect Dis</source><volume>65</volume><year>2017</year><fpage>675</fpage><lpage>679</lpage><pub-id pub-id-type="pmid">28575307</pub-id></element-citation></ref><ref id="bib135"><label>135</label><element-citation publication-type="journal" id="sbref1350"><person-group person-group-type="author"><name><surname>Hui</surname><given-names>DS</given-names></name><name><surname>Peiris</surname><given-names>M</given-names></name></person-group><article-title>Middle East respiratory syndrome</article-title><source>Am J Respir Crit Care Med</source><volume>192</volume><year>2015</year><fpage>278</fpage><lpage>279</lpage><pub-id pub-id-type="pmid">26120749</pub-id></element-citation></ref><ref id="bib136"><label>136</label><element-citation publication-type="journal" id="sbref1360"><person-group person-group-type="author"><name><surname>Nam</surname><given-names>HS</given-names></name><name><surname>Park</surname><given-names>JW</given-names></name><name><surname>Ki</surname><given-names>M</given-names></name><name><surname>Yeon</surname><given-names>MY</given-names></name><name><surname>Kim</surname><given-names>J</given-names></name><name><surname>Kim</surname><given-names>SW</given-names></name></person-group><article-title>High fatality rates and associated factors in two hospital outbreaks of MERS in Daejeon, the Republic of Korea</article-title><source>Int J Infect Dis</source><volume>58</volume><year>2017</year><fpage>37</fpage><lpage>42</lpage><pub-id pub-id-type="pmid">28223175</pub-id></element-citation></ref><ref id="bib137"><label>137</label><element-citation publication-type="journal" id="sbref1370"><person-group person-group-type="author"><name><surname>Oboho</surname><given-names>IK</given-names></name><name><surname>Tomczyk</surname><given-names>SM</given-names></name><name><surname>Al-Asmari</surname><given-names>AM</given-names></name></person-group><article-title>2014 MERS-CoV outbreak in Jeddah—a link to health care facilities</article-title><source>N Engl J Med</source><volume>372</volume><year>2015</year><fpage>846</fpage><lpage>854</lpage><pub-id pub-id-type="pmid">25714162</pub-id></element-citation></ref><ref id="bib138"><label>138</label><element-citation publication-type="journal" id="sbref1380"><person-group person-group-type="author"><name><surname>Hunter</surname><given-names>JC</given-names></name><name><surname>Nguyen</surname><given-names>D</given-names></name><name><surname>Aden</surname><given-names>B</given-names></name></person-group><article-title>Transmission of Middle East respiratory syndrome coronavirus infections in healthcare settings, Abu Dhabi</article-title><source>Emerg Infect Dis</source><volume>22</volume><year>2016</year><fpage>647</fpage><lpage>656</lpage><pub-id pub-id-type="pmid">26981708</pub-id></element-citation></ref><ref id="bib139"><label>139</label><element-citation publication-type="journal" id="sbref1390"><person-group person-group-type="author"><name><surname>Jo</surname><given-names>S</given-names></name><name><surname>Kim</surname><given-names>H</given-names></name><name><surname>Kim</surname><given-names>S</given-names></name><name><surname>Shin</surname><given-names>DH</given-names></name><name><surname>Kim</surname><given-names>MS</given-names></name></person-group><article-title>Characteristics of flavonoids as potent MERS-CoV 3c-like protease inhibitors</article-title><source>Chem Biol Drug Des</source><volume>94</volume><year>2019</year><fpage>2023</fpage><lpage>2030</lpage><pub-id pub-id-type="pmid">31436895</pub-id></element-citation></ref><ref id="bib140"><label>140</label><element-citation publication-type="journal" id="sbref1400"><person-group person-group-type="author"><name><surname>Mustafa</surname><given-names>S</given-names></name><name><surname>Balkhy</surname><given-names>H</given-names></name><name><surname>Gabere</surname><given-names>MN</given-names></name></person-group><article-title>Current treatment options and the role of peptides as potential therapeutic components for Middle East respiratory syndrome (MERS): a review</article-title><source>J Infect Public Health</source><volume>11</volume><year>2018</year><fpage>9</fpage><lpage>17</lpage><pub-id pub-id-type="pmid">28864360</pub-id></element-citation></ref><ref id="bib141"><label>141</label><element-citation publication-type="journal" id="sbref1410"><person-group person-group-type="author"><name><surname>Agostini</surname><given-names>ML</given-names></name><name><surname>Pruijssers</surname><given-names>AJ</given-names></name><name><surname>Chappell</surname><given-names>JD</given-names></name></person-group><article-title>Small-molecule antiviral beta-d-n<sup>4</sup>-hydroxycytidine inhibits a proofreading-intact coronavirus with a high genetic barrier to resistance</article-title><source>J Virol</source><volume>93</volume><year>2019</year><fpage>e01348</fpage><lpage>e01419</lpage><pub-id pub-id-type="pmid">31578288</pub-id></element-citation></ref><ref id="bib142"><label>142</label><element-citation publication-type="journal" id="sbref1420"><person-group person-group-type="author"><name><surname>Sheahan</surname><given-names>TP</given-names></name><name><surname>Sims</surname><given-names>AC</given-names></name><name><surname>Graham</surname><given-names>RL</given-names></name></person-group><article-title>Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses</article-title><source>Sci Transl Med</source><volume>9</volume><year>2017</year><object-id pub-id-type="publisher-id">eaal3653</object-id></element-citation></ref><ref id="bib143"><label>143</label><element-citation publication-type="journal" id="sbref1430"><person-group person-group-type="author"><name><surname>Taylor</surname><given-names>R</given-names></name><name><surname>Kotian</surname><given-names>P</given-names></name><name><surname>Warren</surname><given-names>T</given-names></name></person-group><article-title>BCX4430—a broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease</article-title><source>J Infect Public Health</source><volume>9</volume><year>2016</year><fpage>220</fpage><lpage>226</lpage><pub-id pub-id-type="pmid">27095300</pub-id></element-citation></ref></ref-list><sec id="sec1" sec-type="supplementary-material"><title>Supplementary Material</title><p id="para2010"><supplementary-material content-type="local-data" id="ecomp10"><caption><title>Supplementary appendix</title></caption><media xlink:href="mmc1.pdf"></media></supplementary-material></p></sec><ack id="ceack10"><sec><title>Acknowledgments</title><p>AZ acknowledges support from the <funding-source id="GS1">PANDORA-ID-NET</funding-source> (grant RIA2016E-1609) funded by the European and Developing Countries Clinical Trials Partnership (EDCTP2) under Horizon 2020, the EU's Framework Programme for Research and Innovation. AZ is the recipient of a UK National Institutes of Health Research senior investigator award. SP is supported by grants from the US <funding-source id="GS2">National Institutes of Health</funding-source> (PO1 AI060699 RO1 AI129269). We thank Samantha Mackin (University of Iowa) for creating <xref rid="fig1" ref-type="fig">figure 1</xref> on the basis of a template provided by Benjamin W Neuman (Texas A&M-Texarkana) and Michael J Buchmeier (University of California, Irvine).</p><p>Editorial note: the <italic>Lancet</italic> Group takes a neutral position with respect to territorial claims in published maps and institutional affiliations.</p></sec></ack><ack><title>Contributors</title><p>This paper was conceptualised by ZAM and AZ. All authors contributed equally to the literature search, writing, and reviewing of the manuscript.</p></ack><ack><title>Declaration of interests</title><p>We declare no competing interests.</p></ack></back></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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