Serveur d'exploration MERS

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Clinical features and viral diagnosis of two cases of infection with Middle East Respiratory Syndrome coronavirus: a report of nosocomial transmission

Identifieur interne : 002061 ( Main/Merge ); précédent : 002060; suivant : 002062

Clinical 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] ; Valérie Caro [France] ; Alexandra Mailles [France] ; Didier Che [France] ; Jean-Claude Manuguerra [France] ; Daniel Mathieu [France] ; Arnaud Fontanet [France] ; Sylvie Van Der Werf [France]

Source :

RBID : PMC:7159298

Descripteurs français

English descriptors

Abstract

SummaryBackground

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.

Funding

French Institute for Public Health Surveillance, ANR grant Labex Integrative Biology of Emerging Infectious Diseases, and the European Community's Seventh Framework Programme projects EMPERIE and PREDEMICS.


Url:
DOI: 10.1016/S0140-6736(13)60982-4
PubMed: 23727167
PubMed Central: 7159298

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PMC:7159298

Le document en format XML

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<settlement type="city">Douai</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Ettahar, Nicolas" sort="Ettahar, Nicolas" uniqKey="Ettahar N" first="Nicolas" last="Ettahar">Nicolas Ettahar</name>
<affiliation wicri:level="3">
<nlm:aff id="aff5">Unité de Maladies Infectieuses, Centre Hospitalier de Valenciennes, Valenciennes, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Unité de Maladies Infectieuses, Centre Hospitalier de Valenciennes, Valenciennes</wicri:regionArea>
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<author>
<name sortKey="Lemaire, Xavier" sort="Lemaire, Xavier" uniqKey="Lemaire X" first="Xavier" last="Lemaire">Xavier Lemaire</name>
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<nlm:aff id="aff3">Service de Maladies Infectieuses, Centre Hospitalier de Douai, Douai, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Service de Maladies Infectieuses, Centre Hospitalier de Douai, Douai</wicri:regionArea>
<placeName>
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<region type="old region">Nord-Pas-de-Calais</region>
<settlement type="city">Douai</settlement>
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</author>
<author>
<name sortKey="Vuotto, Fanny" sort="Vuotto, Fanny" uniqKey="Vuotto F" first="Fanny" last="Vuotto">Fanny Vuotto</name>
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<nlm:aff id="aff1">Service de Gestion du Risque Infectieux, Vigilances et Infectiologie, Hopital Huriez, Pavillon Fourrier, Centre Hospitalier Régional et Universitaire de Lille, Université de Lille 2, Lille Cedex, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Service de Gestion du Risque Infectieux, Vigilances et Infectiologie, Hopital Huriez, Pavillon Fourrier, Centre Hospitalier Régional et Universitaire de Lille, Université de Lille 2, Lille Cedex</wicri:regionArea>
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<wicri:noRegion>Lille Cedex</wicri:noRegion>
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</author>
<author>
<name sortKey="Goffard, Anne" sort="Goffard, Anne" uniqKey="Goffard A" first="Anne" last="Goffard">Anne Goffard</name>
<affiliation wicri:level="1">
<nlm:aff id="aff6">Laboratoire de Virologie, Centre de Biologie Pathologie, Centre Hospitalier Régional et Universitaire de Lille, Université de Lille 2, Lille Cedex, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Laboratoire de Virologie, Centre de Biologie Pathologie, Centre Hospitalier Régional et Universitaire de Lille, Université de Lille 2, Lille Cedex</wicri:regionArea>
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<wicri:noRegion>Lille Cedex</wicri:noRegion>
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</author>
<author>
<name sortKey="Behillil, Sylvie" sort="Behillil, Sylvie" uniqKey="Behillil S" first="Sylvie" last="Behillil">Sylvie Behillil</name>
<affiliation wicri:level="3">
<nlm:aff id="aff7">Institut Pasteur, National Reference Center for Influenza Viruses and Unit of Molecular Genetics of RNA Viruses, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Pasteur, National Reference Center for Influenza Viruses and Unit of Molecular Genetics of RNA Viruses, Paris</wicri:regionArea>
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<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
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<affiliation wicri:level="3">
<nlm:aff id="aff8">Université Paris Diderot Sorbonne Paris Cité, Unit of Molecular Genetics of RNA Viruses, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Paris Diderot Sorbonne Paris Cité, Unit of Molecular Genetics of RNA Viruses, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="aff9">Centre National de la Recherche Scientifique UMR3569, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Centre National de la Recherche Scientifique UMR3569, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Enouf, Vincent" sort="Enouf, Vincent" uniqKey="Enouf V" first="Vincent" last="Enouf">Vincent Enouf</name>
<affiliation wicri:level="3">
<nlm:aff id="aff7">Institut Pasteur, National Reference Center for Influenza Viruses and Unit of Molecular Genetics of RNA Viruses, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Pasteur, National Reference Center for Influenza Viruses and Unit of Molecular Genetics of RNA Viruses, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
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<affiliation wicri:level="3">
<nlm:aff id="aff8">Université Paris Diderot Sorbonne Paris Cité, Unit of Molecular Genetics of RNA Viruses, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Paris Diderot Sorbonne Paris Cité, Unit of Molecular Genetics of RNA Viruses, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
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<affiliation wicri:level="3">
<nlm:aff id="aff9">Centre National de la Recherche Scientifique UMR3569, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Centre National de la Recherche Scientifique UMR3569, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Caro, Valerie" sort="Caro, Valerie" uniqKey="Caro V" first="Valérie" last="Caro">Valérie Caro</name>
<affiliation wicri:level="3">
<nlm:aff id="aff10">Institut Pasteur, Cellule d'Intervention Biologique d'Urgence, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Pasteur, Cellule d'Intervention Biologique d'Urgence, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Mailles, Alexandra" sort="Mailles, Alexandra" uniqKey="Mailles A" first="Alexandra" last="Mailles">Alexandra Mailles</name>
<affiliation wicri:level="1">
<nlm:aff id="aff11">Institut de veille Sanitaire, Saint-Maurice, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut de veille Sanitaire, Saint-Maurice</wicri:regionArea>
<wicri:noRegion>Saint-Maurice</wicri:noRegion>
<wicri:noRegion>Saint-Maurice</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Che, Didier" sort="Che, Didier" uniqKey="Che D" first="Didier" last="Che">Didier Che</name>
<affiliation wicri:level="1">
<nlm:aff id="aff11">Institut de veille Sanitaire, Saint-Maurice, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut de veille Sanitaire, Saint-Maurice</wicri:regionArea>
<wicri:noRegion>Saint-Maurice</wicri:noRegion>
<wicri:noRegion>Saint-Maurice</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Manuguerra, Jean Claude" sort="Manuguerra, Jean Claude" uniqKey="Manuguerra J" first="Jean-Claude" last="Manuguerra">Jean-Claude Manuguerra</name>
<affiliation wicri:level="3">
<nlm:aff id="aff10">Institut Pasteur, Cellule d'Intervention Biologique d'Urgence, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Pasteur, Cellule d'Intervention Biologique d'Urgence, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author>
<name sortKey="Mathieu, Daniel" sort="Mathieu, Daniel" uniqKey="Mathieu D" first="Daniel" last="Mathieu">Daniel Mathieu</name>
<affiliation wicri:level="1">
<nlm:aff id="aff2">Pôle de Réanimation, Hôpital Roger Salengro, Centre Hospitalier Régional et Universitaire de Lille, Université de Lille 2, Lille Cedex, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Pôle de Réanimation, Hôpital Roger Salengro, Centre Hospitalier Régional et Universitaire de Lille, Université de Lille 2, Lille Cedex</wicri:regionArea>
<wicri:noRegion>Lille Cedex</wicri:noRegion>
<wicri:noRegion>Lille Cedex</wicri:noRegion>
</affiliation>
</author>
<author>
<name sortKey="Fontanet, Arnaud" sort="Fontanet, Arnaud" uniqKey="Fontanet A" first="Arnaud" last="Fontanet">Arnaud Fontanet</name>
<affiliation wicri:level="3">
<nlm:aff id="aff12">Conservatoire National des Arts et Métiers, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Conservatoire National des Arts et Métiers, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="aff13">Institut Pasteur, Emerging Diseases Epidemiology Unit, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Pasteur, Emerging Diseases Epidemiology Unit, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<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>
<affiliation wicri:level="3">
<nlm:aff id="aff7">Institut Pasteur, National Reference Center for Influenza Viruses and Unit of Molecular Genetics of RNA Viruses, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Pasteur, National Reference Center for Influenza Viruses and Unit of Molecular Genetics of RNA Viruses, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="aff8">Université Paris Diderot Sorbonne Paris Cité, Unit of Molecular Genetics of RNA Viruses, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Paris Diderot Sorbonne Paris Cité, Unit of Molecular Genetics of RNA Viruses, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3">
<nlm:aff id="aff9">Centre National de la Recherche Scientifique UMR3569, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Centre National de la Recherche Scientifique UMR3569, Paris</wicri:regionArea>
<placeName>
<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
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</analytic>
<series>
<title level="j">Lancet (London, England)</title>
<idno type="ISSN">0140-6736</idno>
<idno type="eISSN">1474-547X</idno>
<imprint>
<date when="2013">2013</date>
</imprint>
</series>
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<term>Coronavirus (genetics)</term>
<term>Coronavirus Infections (diagnosis)</term>
<term>Coronavirus Infections (diagnostic imaging)</term>
<term>Coronavirus Infections (transmission)</term>
<term>Coronavirus Infections (virology)</term>
<term>Cross Infection (diagnosis)</term>
<term>Cross Infection (diagnostic imaging)</term>
<term>Cross Infection (transmission)</term>
<term>Cross Infection (virology)</term>
<term>Fatal Outcome</term>
<term>France (epidemiology)</term>
<term>Humans</term>
<term>Infectious Disease Incubation Period</term>
<term>Lung (diagnostic imaging)</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Radiography</term>
<term>Real-Time Polymerase Chain Reaction</term>
<term>Travel</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Adulte d'âge moyen</term>
<term>Coronavirus (génétique)</term>
<term>France (épidémiologie)</term>
<term>Humains</term>
<term>Infection croisée (diagnostic)</term>
<term>Infection croisée (imagerie diagnostique)</term>
<term>Infection croisée (transmission)</term>
<term>Infection croisée (virologie)</term>
<term>Infections à coronavirus (diagnostic)</term>
<term>Infections à coronavirus (imagerie diagnostique)</term>
<term>Infections à coronavirus (transmission)</term>
<term>Infections à coronavirus (virologie)</term>
<term>Issue fatale</term>
<term>Mâle</term>
<term>Poumon (imagerie diagnostique)</term>
<term>Période d'incubation de maladie infectieuse</term>
<term>Radiographie</term>
<term>Réaction de polymérisation en chaine en temps réel</term>
<term>Voyage</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnosis" xml:lang="en">
<term>Coronavirus Infections</term>
<term>Cross Infection</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnostic" xml:lang="fr">
<term>Infection croisée</term>
<term>Infections à coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnostic imaging" xml:lang="en">
<term>Coronavirus Infections</term>
<term>Cross Infection</term>
<term>Lung</term>
</keywords>
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<term>France</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="imagerie diagnostique" xml:lang="fr">
<term>Infection croisée</term>
<term>Infections à coronavirus</term>
<term>Poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="transmission" xml:lang="en">
<term>Coronavirus Infections</term>
<term>Cross Infection</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr">
<term>Infection croisée</term>
<term>Infections à coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en">
<term>Coronavirus Infections</term>
<term>Cross Infection</term>
</keywords>
<keywords scheme="MESH" qualifier="épidémiologie" xml:lang="fr">
<term>France</term>
<term>Infection croisée</term>
<term>Infections à coronavirus</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Fatal Outcome</term>
<term>Humans</term>
<term>Infectious Disease Incubation Period</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Radiography</term>
<term>Real-Time Polymerase Chain Reaction</term>
<term>Travel</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Adulte d'âge moyen</term>
<term>Humains</term>
<term>Issue fatale</term>
<term>Mâle</term>
<term>Période d'incubation de maladie infectieuse</term>
<term>Radiographie</term>
<term>Réaction de polymérisation en chaine en temps réel</term>
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<front>
<div type="abstract" xml:lang="en">
<title>Summary</title>
<sec>
<title>Background</title>
<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.</p>
</sec>
<sec>
<title>Methods</title>
<p>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.</p>
</sec>
<sec>
<title>Findings</title>
<p>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.</p>
</sec>
<sec>
<title>Interpretation</title>
<p>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>
</sec>
<sec>
<title>Funding</title>
<p>French Institute for Public Health Surveillance, ANR grant Labex Integrative Biology of Emerging Infectious Diseases, and the European Community's Seventh Framework Programme projects EMPERIE and PREDEMICS.</p>
</sec>
</div>
</front>
<back>
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<name sortKey="Che, Didier" sort="Che, Didier" uniqKey="Che D" first="Didier" last="Che">Didier Che</name>
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<name sortKey="Mathieu, Daniel" sort="Mathieu, Daniel" uniqKey="Mathieu D" first="Daniel" last="Mathieu">Daniel Mathieu</name>
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<name sortKey="Fontanet, Arnaud" sort="Fontanet, Arnaud" uniqKey="Fontanet A" first="Arnaud" last="Fontanet">Arnaud Fontanet</name>
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<orgName>Conservatoire National des Arts et Métiers [CNAM]</orgName>
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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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<orgName type="acronym">CNR</orgName>
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<addrLine>25-28, rue du Docteur Roux 75724 Paris Cedex 15</addrLine>
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</address>
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<orgName>Institut Pasteur [Paris]</orgName>
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<country>France</country>
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</author>
<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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<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>
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<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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<name sortKey="Guery, Benoit" sort="Guery, Benoit" uniqKey="Guery B" first="Benoit" last="Guery">Benoit Guery</name>
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<nlm:aff id="aff1">Service de Gestion du Risque Infectieux, Vigilances et Infectiologie, Hopital Huriez, Pavillon Fourrier, Centre Hospitalier Régional et Universitaire de Lille, Université de Lille 2, Lille Cedex, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Service de Gestion du Risque Infectieux, Vigilances et Infectiologie, Hopital Huriez, Pavillon Fourrier, Centre Hospitalier Régional et Universitaire de Lille, Université de Lille 2, Lille Cedex</wicri:regionArea>
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<name sortKey="Poissy, Julien" sort="Poissy, Julien" uniqKey="Poissy J" first="Julien" last="Poissy">Julien Poissy</name>
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<nlm:aff id="aff2">Pôle de Réanimation, Hôpital Roger Salengro, Centre Hospitalier Régional et Universitaire de Lille, Université de Lille 2, Lille Cedex, France</nlm:aff>
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<name sortKey="El Mansouf, Loubna" sort="El Mansouf, Loubna" uniqKey="El Mansouf L" first="Loubna" last="El Mansouf">Loubna El Mansouf</name>
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<name sortKey="Sejourne, Caroline" sort="Sejourne, Caroline" uniqKey="Sejourne C" first="Caroline" last="Séjourné">Caroline Séjourné</name>
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<name sortKey="Ettahar, Nicolas" sort="Ettahar, Nicolas" uniqKey="Ettahar N" first="Nicolas" last="Ettahar">Nicolas Ettahar</name>
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<name sortKey="Lemaire, Xavier" sort="Lemaire, Xavier" uniqKey="Lemaire X" first="Xavier" last="Lemaire">Xavier Lemaire</name>
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<name sortKey="Mailles, Alexandra" sort="Mailles, Alexandra" uniqKey="Mailles A" first="Alexandra" last="Mailles">Alexandra Mailles</name>
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<title xml:lang="en" level="a" type="main">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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<name sortKey="Guery, Benoit" sort="Guery, Benoit" uniqKey="Guery B" first="Benoit" last="Guery">Benoit Guery</name>
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<name sortKey="Mailles, Alexandra" sort="Mailles, Alexandra" uniqKey="Mailles A" first="Alexandra" last="Mailles">Alexandra Mailles</name>
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<name sortKey="Che, Didier" sort="Che, Didier" uniqKey="Che D" first="Didier" last="Che">Didier Che</name>
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<nlm:aff id="aff11">Institut de veille Sanitaire, Saint-Maurice, France</nlm:aff>
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<wicri:noRegion>Saint-Maurice</wicri:noRegion>
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<name sortKey="Manuguerra, Jean Claude" sort="Manuguerra, Jean Claude" uniqKey="Manuguerra J" first="Jean-Claude" last="Manuguerra">Jean-Claude Manuguerra</name>
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<nlm:aff id="aff10">Institut Pasteur, Cellule d'Intervention Biologique d'Urgence, Paris, France</nlm:aff>
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<wicri:regionArea>Institut Pasteur, Cellule d'Intervention Biologique d'Urgence, Paris</wicri:regionArea>
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<name sortKey="Mathieu, Daniel" sort="Mathieu, Daniel" uniqKey="Mathieu D" first="Daniel" last="Mathieu">Daniel Mathieu</name>
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<nlm:aff id="aff2">Pôle de Réanimation, Hôpital Roger Salengro, Centre Hospitalier Régional et Universitaire de Lille, Université de Lille 2, Lille Cedex, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Pôle de Réanimation, Hôpital Roger Salengro, Centre Hospitalier Régional et Universitaire de Lille, Université de Lille 2, Lille Cedex</wicri:regionArea>
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<wicri:noRegion>Lille Cedex</wicri:noRegion>
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<name sortKey="Fontanet, Arnaud" sort="Fontanet, Arnaud" uniqKey="Fontanet A" first="Arnaud" last="Fontanet">Arnaud Fontanet</name>
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<nlm:aff id="aff12">Conservatoire National des Arts et Métiers, Paris, France</nlm:aff>
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<region type="region">Île-de-France</region>
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<nlm:aff id="aff13">Institut Pasteur, Emerging Diseases Epidemiology Unit, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Pasteur, Emerging Diseases Epidemiology Unit, Paris</wicri:regionArea>
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<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
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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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<nlm:aff id="aff7">Institut Pasteur, National Reference Center for Influenza Viruses and Unit of Molecular Genetics of RNA Viruses, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Institut Pasteur, National Reference Center for Influenza Viruses and Unit of Molecular Genetics of RNA Viruses, Paris</wicri:regionArea>
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<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
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<affiliation wicri:level="3">
<nlm:aff id="aff8">Université Paris Diderot Sorbonne Paris Cité, Unit of Molecular Genetics of RNA Viruses, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Paris Diderot Sorbonne Paris Cité, Unit of Molecular Genetics of RNA Viruses, Paris</wicri:regionArea>
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<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
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<affiliation wicri:level="3">
<nlm:aff id="aff9">Centre National de la Recherche Scientifique UMR3569, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Centre National de la Recherche Scientifique UMR3569, Paris</wicri:regionArea>
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<region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
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<series>
<title level="j">Lancet (London, England)</title>
<idno type="ISSN">0140-6736</idno>
<idno type="eISSN">1474-547X</idno>
<imprint>
<date when="2013">2013</date>
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<keywords scheme="KwdEn" xml:lang="en">
<term>Coronavirus (genetics)</term>
<term>Coronavirus Infections (diagnosis)</term>
<term>Coronavirus Infections (diagnostic imaging)</term>
<term>Coronavirus Infections (transmission)</term>
<term>Coronavirus Infections (virology)</term>
<term>Cross Infection (diagnosis)</term>
<term>Cross Infection (diagnostic imaging)</term>
<term>Cross Infection (transmission)</term>
<term>Cross Infection (virology)</term>
<term>Fatal Outcome</term>
<term>France (epidemiology)</term>
<term>Humans</term>
<term>Infectious Disease Incubation Period</term>
<term>Lung (diagnostic imaging)</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Radiography</term>
<term>Real-Time Polymerase Chain Reaction</term>
<term>Travel</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr">
<term>Adulte d'âge moyen</term>
<term>Coronavirus (génétique)</term>
<term>France (épidémiologie)</term>
<term>Humains</term>
<term>Infection croisée (diagnostic)</term>
<term>Infection croisée (imagerie diagnostique)</term>
<term>Infection croisée (transmission)</term>
<term>Infection croisée (virologie)</term>
<term>Infections à coronavirus (diagnostic)</term>
<term>Infections à coronavirus (imagerie diagnostique)</term>
<term>Infections à coronavirus (transmission)</term>
<term>Infections à coronavirus (virologie)</term>
<term>Issue fatale</term>
<term>Mâle</term>
<term>Poumon (imagerie diagnostique)</term>
<term>Période d'incubation de maladie infectieuse</term>
<term>Radiographie</term>
<term>Réaction de polymérisation en chaine en temps réel</term>
<term>Voyage</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnosis" xml:lang="en">
<term>Coronavirus Infections</term>
<term>Cross Infection</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnostic" xml:lang="fr">
<term>Infection croisée</term>
<term>Infections à coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="diagnostic imaging" xml:lang="en">
<term>Coronavirus Infections</term>
<term>Cross Infection</term>
<term>Lung</term>
</keywords>
<keywords scheme="MESH" qualifier="epidemiology" xml:lang="en">
<term>France</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en">
<term>Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr">
<term>Coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="imagerie diagnostique" xml:lang="fr">
<term>Infection croisée</term>
<term>Infections à coronavirus</term>
<term>Poumon</term>
</keywords>
<keywords scheme="MESH" qualifier="transmission" xml:lang="en">
<term>Coronavirus Infections</term>
<term>Cross Infection</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr">
<term>Infection croisée</term>
<term>Infections à coronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en">
<term>Coronavirus Infections</term>
<term>Cross Infection</term>
</keywords>
<keywords scheme="MESH" qualifier="épidémiologie" xml:lang="fr">
<term>France</term>
<term>Infection croisée</term>
<term>Infections à coronavirus</term>
</keywords>
<keywords scheme="MESH" xml:lang="en">
<term>Fatal Outcome</term>
<term>Humans</term>
<term>Infectious Disease Incubation Period</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Radiography</term>
<term>Real-Time Polymerase Chain Reaction</term>
<term>Travel</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Adulte d'âge moyen</term>
<term>Humains</term>
<term>Issue fatale</term>
<term>Mâle</term>
<term>Période d'incubation de maladie infectieuse</term>
<term>Radiographie</term>
<term>Réaction de polymérisation en chaine en temps réel</term>
<term>Voyage</term>
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<div type="abstract" xml:lang="en">
<title>Summary</title>
<sec>
<title>Background</title>
<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.</p>
</sec>
<sec>
<title>Methods</title>
<p>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.</p>
</sec>
<sec>
<title>Findings</title>
<p>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.</p>
</sec>
<sec>
<title>Interpretation</title>
<p>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>
</sec>
<sec>
<title>Funding</title>
<p>French Institute for Public Health Surveillance, ANR grant Labex Integrative Biology of Emerging Infectious Diseases, and the European Community's Seventh Framework Programme projects EMPERIE and PREDEMICS.</p>
</sec>
</div>
</front>
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