Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission
Identifieur interne : 000001 ( Hal/Curation ); précédent : 000000; suivant : 000002Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission
Auteurs : Benoit Guery [France] ; Julien Poissy [France] ; Loubna El Mansouf [France] ; Caroline Séjourné [France] ; Nicolas Ettahar [France] ; Xavier Lemaire [France] ; Fanny Vuotto [France] ; Anne Goffard [France] ; Sylvie Behillil [France] ; Vincent Enouf [France] ; Valerie Caro [France] ; Alexandra Mailles [France] ; Didier Che [France] ; Jean-Claude Manuguerra [France] ; Daniel Mathieu [France] ; Arnaud Fontanet [France] ; Sylvie Van Der Werf [France] ; The Mers-Cov GroupSource :
- The Lancet [ 0923-7577 ] ; 2013-06.
Abstract
Human infection with a novel coronavirus named Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia and the Middle East in September, 2012, with 44 laboratory-confirmed cases as of May 23, 2013. We report detailed clinical and virological data for two related cases of MERS-CoV disease, after nosocomial transmission of the virus from one patient to another in a French hospital.METHODS:Patient 1 visited Dubai in April, 2013; patient 2 lives in France and did not travel abroad. Both patients had underlying immunosuppressive disorders. We tested specimens from the upper (nasopharyngeal swabs) or the lower (bronchoalveolar lavage, sputum) respiratory tract and whole blood, plasma, and serum specimens for MERS-CoV by real-time RT-PCR targeting the upE and Orf1A genes of MERS-CoV.FINDINGS:Initial clinical presentation included fever, chills, and myalgia in both patients, and for patient 1, diarrhoea. Respiratory symptoms rapidly became predominant with acute respiratory failure leading to mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Both patients developed acute renal failure. MERS-CoV was detected in lower respiratory tract specimens with high viral load (eg, cycle threshold [Ct] values of 22·9 for upE and 24 for Orf1a for a bronchoalveolar lavage sample from patient 1; Ct values of 22·5 for upE and 23·9 for Orf1a for an induced sputum sample from patient 2), whereas nasopharyngeal specimens were weakly positive or inconclusive. The two patients shared the same room for 3 days. The incubation period was estimated at 9-12 days for the second case. No secondary transmission was documented in hospital staff despite the absence of specific protective measures before the diagnosis of MERS-CoV was suspected. Patient 1 died on May 28, due to refractory multiple organ failure.INTERPRETATION:Patients with respiratory symptoms returning from the Middle East or exposed to a confirmed case should be isolated and investigated for MERS-CoV with lower respiratory tract sample analysis and an assumed incubation period of 12 days. Immunosuppression should also be taken into account as a risk factor.
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DOI: 10.1016/S0140-6736(13)60982-4
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<author><name sortKey="Mailles, Alexandra" sort="Mailles, Alexandra" uniqKey="Mailles A" first="Alexandra" last="Mailles">Alexandra Mailles</name>
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<author><name sortKey="Fontanet, Arnaud" sort="Fontanet, Arnaud" uniqKey="Fontanet A" first="Arnaud" last="Fontanet">Arnaud Fontanet</name>
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<author><name sortKey="Van Der Werf, Sylvie" sort="Van Der Werf, Sylvie" uniqKey="Van Der Werf S" first="Sylvie" last="Van Der Werf">Sylvie Van Der Werf</name>
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<author><name sortKey="Mers Cov Group, The" sort="Mers Cov Group, The" uniqKey="Mers Cov Group T" first="The" last="Mers-Cov Group">The Mers-Cov Group</name>
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<idno type="DOI">10.1016/S0140-6736(13)60982-4</idno>
<series><title level="j">The Lancet</title>
<idno type="ISSN">0923-7577</idno>
<imprint><date type="datePub">2013-06</date>
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<front><div type="abstract" xml:lang="en"> <p>Human infection with a novel coronavirus named Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia and the Middle East in September, 2012, with 44 laboratory-confirmed cases as of May 23, 2013. We report detailed clinical and virological data for two related cases of MERS-CoV disease, after nosocomial transmission of the virus from one patient to another in a French hospital.METHODS:Patient 1 visited Dubai in April, 2013; patient 2 lives in France and did not travel abroad. Both patients had underlying immunosuppressive disorders. We tested specimens from the upper (nasopharyngeal swabs) or the lower (bronchoalveolar lavage, sputum) respiratory tract and whole blood, plasma, and serum specimens for MERS-CoV by real-time RT-PCR targeting the upE and Orf1A genes of MERS-CoV.FINDINGS:Initial clinical presentation included fever, chills, and myalgia in both patients, and for patient 1, diarrhoea. Respiratory symptoms rapidly became predominant with acute respiratory failure leading to mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Both patients developed acute renal failure. MERS-CoV was detected in lower respiratory tract specimens with high viral load (eg, cycle threshold [Ct] values of 22·9 for upE and 24 for Orf1a for a bronchoalveolar lavage sample from patient 1; Ct values of 22·5 for upE and 23·9 for Orf1a for an induced sputum sample from patient 2), whereas nasopharyngeal specimens were weakly positive or inconclusive. The two patients shared the same room for 3 days. The incubation period was estimated at 9-12 days for the second case. No secondary transmission was documented in hospital staff despite the absence of specific protective measures before the diagnosis of MERS-CoV was suspected. Patient 1 died on May 28, due to refractory multiple organ failure.INTERPRETATION:Patients with respiratory symptoms returning from the Middle East or exposed to a confirmed case should be isolated and investigated for MERS-CoV with lower respiratory tract sample analysis and an assumed incubation period of 12 days. Immunosuppression should also be taken into account as a risk factor.</p>
</div>
</front>
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<hal api="V3"> <titleStmt> <title xml:lang="en">Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission</title>
<author role="aut"> <persName> <forename type="first">Benoit</forename>
<surname>Guery</surname>
</persName>
<idno type="halauthorid">178418</idno>
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</author>
<author role="aut"> <persName> <forename type="first">Julien</forename>
<surname>Poissy</surname>
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</author>
<author role="aut"> <persName> <forename type="first">Loubna</forename>
<surname>el Mansouf</surname>
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<author role="aut"> <persName> <forename type="first">Caroline</forename>
<surname>Séjourné</surname>
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<author role="aut"> <persName> <forename type="first">Nicolas</forename>
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<author role="aut"> <persName> <forename type="first">Xavier</forename>
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<author role="aut"> <persName> <forename type="first">Fanny</forename>
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<author role="aut"> <persName> <forename type="first">Anne</forename>
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</author>
<author role="aut"> <persName> <forename type="first">Sylvie</forename>
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<author role="aut"> <persName> <forename type="first">Vincent</forename>
<surname>Enouf</surname>
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<affiliation ref="#struct-481195"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Valerie</forename>
<surname>Caro</surname>
</persName>
<idno type="halauthorid">204629</idno>
<affiliation ref="#struct-31437"></affiliation>
</author>
<author role="aut"> <persName> <forename type="first">Alexandra</forename>
<surname>Mailles</surname>
</persName>
<email type="md5">75de7164585cdda503ebd9fa8762aec3</email>
<email type="domain">invs.sante.fr</email>
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<author role="aut"> <persName> <forename type="first">Didier</forename>
<surname>Che</surname>
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<idno type="halauthorid">570807</idno>
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</author>
<author role="aut"> <persName> <forename type="first">Jean-Claude</forename>
<surname>Manuguerra</surname>
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<idno type="halauthorid">202084</idno>
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</author>
<author role="aut"> <persName> <forename type="first">Daniel</forename>
<surname>Mathieu</surname>
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<idno type="halauthorid">363191</idno>
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</author>
<author role="aut"> <persName> <forename type="first">Arnaud</forename>
<surname>Fontanet</surname>
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<idno type="halauthorid">117989</idno>
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<author role="aut"> <persName> <forename type="first">Sylvie</forename>
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<idno type="halauthorid">202082</idno>
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<affiliation ref="#struct-481195"></affiliation>
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<author role="aut"> <persName> <forename type="first">the</forename>
<surname>MERS-CoV group</surname>
</persName>
<idno type="halauthorid">11664481</idno>
</author>
<editor role="depositor"> <persName> <forename>Anne</forename>
<surname>Goffard</surname>
</persName>
<email type="md5">1f1f6670bfbb3e6b1ec674437578a5f3</email>
<email type="domain">univ-lille.fr</email>
</editor>
<funder ref="#projanr-37850"></funder>
<funder ref="#projeurop-18734"></funder>
<funder ref="#projeurop-89460"></funder>
<funder>The National Reference Center for Influenza Viruses and the CIBU are supported in part by funds from the French Institute for Public Health Surveillance (Institut de veille sanitaire, InVS). Work related to collection of data, implementation of the assays, and sequencing was done with funds from ANR grant Labex Integrative Biology of Emerging Infectious Diseases (IBEID, grant number ANR-10-LABX-62-IBEID from the French Government's Investissement d'Avenir programme) and from the European Community's Seventh Framework Programme (FP7/2007–2013) under the project EMPERIE (European Community grant agreement number 223498) and under the project PREDEMICS (grant agreement number 278433)</funder>
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<editionStmt> <edition n="v1" type="current"> <date type="whenSubmitted">2019-08-16 10:15:27</date>
<date type="whenModified">2020-04-20 14:46:02</date>
<date type="whenReleased">2019-08-16 10:15:27</date>
<date type="whenProduced">2013-06</date>
<ref type="externalLink" target="http://www.thelancet.com/article/S0140673613609824/pdf"></ref>
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<idno type="halRefHtml">The Lancet, Elsevier, 2013, 381 (9885), pp.2265-2272. ⟨10.1016/S0140-6736(13)60982-4⟩</idno>
<idno type="halRef">The Lancet, Elsevier, 2013, 381 (9885), pp.2265-2272. ⟨10.1016/S0140-6736(13)60982-4⟩</idno>
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<idno type="stamp" n="CNAM">Conservatoire National des Arts et Métiers</idno>
<idno type="stamp" n="UNIV-HESAM-CNAM" corresp="UNIV-HESAM">Conservatoire National des Arts et Métiers</idno>
<idno type="stamp" n="UNIV-PARIS7" corresp="UNIV-PARIS">Université Denis Diderot - Paris VII</idno>
<idno type="stamp" n="USPC">Université Sorbonne Paris Cité</idno>
<idno type="stamp" n="UNIV-HESAM">HESAM Université</idno>
<idno type="stamp" n="PASTEUR">Institut Pasteur</idno>
<idno type="stamp" n="OPENAIRE">OpenAIRE</idno>
<idno type="stamp" n="UNIV-PARIS">Université de Paris</idno>
<idno type="stamp" n="UP-SCIENCES">Université de Paris - Faculté des Sciences</idno>
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<notesStmt> <note type="commentary">Comment in: Middle East respiratory syndrome: new disease, old lessons. [Lancet. 2013]</note>
<note type="audience" n="2">International</note>
<note type="popular" n="0">No</note>
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<sourceDesc> <biblStruct> <analytic> <title xml:lang="en">Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission</title>
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<author role="aut"> <persName> <forename type="first">Caroline</forename>
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<author role="aut"> <persName> <forename type="first">Fanny</forename>
<surname>Vuotto</surname>
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<email type="domain">free.fr</email>
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<author role="aut"> <persName> <forename type="first">Anne</forename>
<surname>Goffard</surname>
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<idno type="halauthorid">136784</idno>
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<author role="aut"> <persName> <forename type="first">Sylvie</forename>
<surname>Behillil</surname>
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<author role="aut"> <persName> <forename type="first">Vincent</forename>
<surname>Enouf</surname>
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<surname>Caro</surname>
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<author role="aut"> <persName> <forename type="first">Alexandra</forename>
<surname>Mailles</surname>
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<author role="aut"> <persName> <forename type="first">Didier</forename>
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<author role="aut"> <persName> <forename type="first">Jean-Claude</forename>
<surname>Manuguerra</surname>
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<author role="aut"> <persName> <forename type="first">Daniel</forename>
<surname>Mathieu</surname>
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<author role="aut"> <persName> <forename type="first">Sylvie</forename>
<surname>Van Der Werf</surname>
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<author role="aut"> <persName> <forename type="first">the</forename>
<surname>MERS-CoV group</surname>
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<monogr> <idno type="halJournalId" status="VALID">26611</idno>
<idno type="issn">0923-7577</idno>
<title level="j">The Lancet</title>
<imprint> <publisher>Elsevier</publisher>
<biblScope unit="volume">381</biblScope>
<biblScope unit="issue">9885</biblScope>
<biblScope unit="pp">2265-2272</biblScope>
<date type="datePub">2013-06</date>
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<idno type="doi">10.1016/S0140-6736(13)60982-4</idno>
<idno type="pubmed">23727167</idno>
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<classCode scheme="halDomain" n="sdv.mhep.me">Life Sciences [q-bio]/Human health and pathology/Emerging diseases</classCode>
<classCode scheme="halDomain" n="sdv.mhep.mi">Life Sciences [q-bio]/Human health and pathology/Infectious diseases</classCode>
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<abstract xml:lang="en"> <p>Human infection with a novel coronavirus named Middle East Respiratory Syndrome coronavirus (MERS-CoV) was first identified in Saudi Arabia and the Middle East in September, 2012, with 44 laboratory-confirmed cases as of May 23, 2013. We report detailed clinical and virological data for two related cases of MERS-CoV disease, after nosocomial transmission of the virus from one patient to another in a French hospital.METHODS:Patient 1 visited Dubai in April, 2013; patient 2 lives in France and did not travel abroad. Both patients had underlying immunosuppressive disorders. We tested specimens from the upper (nasopharyngeal swabs) or the lower (bronchoalveolar lavage, sputum) respiratory tract and whole blood, plasma, and serum specimens for MERS-CoV by real-time RT-PCR targeting the upE and Orf1A genes of MERS-CoV.FINDINGS:Initial clinical presentation included fever, chills, and myalgia in both patients, and for patient 1, diarrhoea. Respiratory symptoms rapidly became predominant with acute respiratory failure leading to mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Both patients developed acute renal failure. MERS-CoV was detected in lower respiratory tract specimens with high viral load (eg, cycle threshold [Ct] values of 22·9 for upE and 24 for Orf1a for a bronchoalveolar lavage sample from patient 1; Ct values of 22·5 for upE and 23·9 for Orf1a for an induced sputum sample from patient 2), whereas nasopharyngeal specimens were weakly positive or inconclusive. The two patients shared the same room for 3 days. The incubation period was estimated at 9-12 days for the second case. No secondary transmission was documented in hospital staff despite the absence of specific protective measures before the diagnosis of MERS-CoV was suspected. Patient 1 died on May 28, due to refractory multiple organ failure.INTERPRETATION:Patients with respiratory symptoms returning from the Middle East or exposed to a confirmed case should be isolated and investigated for MERS-CoV with lower respiratory tract sample analysis and an assumed incubation period of 12 days. Immunosuppression should also be taken into account as a risk factor.</p>
</abstract>
<particDesc> <org type="consortium">We thank the nurses and all health-care workers from the hospitals in Valenciennes, Douai, and Lille who, in this crisis situation, took care of the patients and controlled the spread of this disease. We thank P Despres, S Paulous, and M P Frenkiel (Unit of Flavivirus-Host Molecular Interactions, Institut Pasteur) for preliminary serological analyses. We thank Eric Kipnis for editing of the report.</org>
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