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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

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          Summary

          Background

          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.

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          Most cited references 9

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          Middle East Respiratory Syndrome Coronavirus (MERS-CoV): Announcement of the Coronavirus Study Group

          Journal of Virology, 87(14), 7790-7792
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            Viral shedding patterns of coronavirus in patients with probable severe acute respiratory syndrome

            Summary Severe acute respiratory syndrome (SARS) is thought to be caused by a novel coronavirus, SARS-associated coronavirus. We studied viral shedding of SARS coronavirus to improve diagnosis and infection control. Reverse-transcriptase PCR was done on 2134 specimens of different types. 355 (45%) specimens of nasopharyngeal aspirates and 150 (28%) of faeces were positive for SARS coronavirus RNA. Positive rates peaked at 6–11 days after onset of illness for nasopharyngeal aspirates (87 of 149 [58%], to 37 of 62 [60%]), and 9–14 days for faeces (15 of 22 [68%], to 26 of 37 [70%]). Overall, peak viral loads were reached at 12–14 days of illness when patients were probably in hospital care, which would explain why hospital workers were prone to infection. Low rate of viral shedding in the first few days of illness meant that early isolation measures would probably be effective.
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              Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections.

              We present a rigorously validated and highly sensitive confirmatory real-time RT-PCR assay (1A assay) that can be used in combination with the previously reported upE assay. Two additional RT-PCR assays for sequencing are described, targeting the RdRp gene (RdRpSeq assay) and N gene (NSeq assay), where an insertion/deletion polymorphism might exist among different hCoV-EMC strains. Finally, a simplified and biologically safe protocol for detection of antibody response by immunofluorescence microscopy was developed using convalescent patient serum.
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                Author and article information

                Contributors
                Journal
                Lancet
                Lancet
                Lancet (London, England)
                Elsevier Ltd.
                0140-6736
                1474-547X
                30 May 2013
                29 June-5 July 2013
                30 May 2013
                : 381
                : 9885
                : 2265-2272
                Affiliations
                [a ]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
                [b ]Pôle de Réanimation, Hôpital Roger Salengro, Centre Hospitalier Régional et Universitaire de Lille, Université de Lille 2, Lille Cedex, France
                [c ]Service de Maladies Infectieuses, Centre Hospitalier de Douai, Douai, France
                [d ]Service de Réanimation, Centre Hospitalier de Douai, Douai, France
                [e ]Unité de Maladies Infectieuses, Centre Hospitalier de Valenciennes, Valenciennes, France
                [f ]Laboratoire de Virologie, Centre de Biologie Pathologie, Centre Hospitalier Régional et Universitaire de Lille, Université de Lille 2, Lille Cedex, France
                [g ]Institut Pasteur, National Reference Center for Influenza Viruses and Unit of Molecular Genetics of RNA Viruses, Paris, France
                [h ]Université Paris Diderot Sorbonne Paris Cité, Unit of Molecular Genetics of RNA Viruses, Paris, France
                [i ]Centre National de la Recherche Scientifique UMR3569, Paris, France
                [j ]Institut Pasteur, Cellule d'Intervention Biologique d'Urgence, Paris, France
                [k ]Institut de veille Sanitaire, Saint-Maurice, France
                [l ]Conservatoire National des Arts et Métiers, Paris, France
                [m ]Institut Pasteur, Emerging Diseases Epidemiology Unit, Paris, France
                Author notes
                [* ]Correspondence to: Dr Sylvie van der Werf, Institut Pasteur, National Reference Center for Influenza Viruses and Unit of Molecular Genetics of RNA Viruses, 75015 Paris, France sylvie.van-der-werf@ 123456pasteur.fr
                [** ]Dr Benoit Guery, Service de Gestion du Risque Infectieux, Vigilances et Infectiologie, Hopital Huriez, Pavillon Fourrier, 59045 Lille Cedex, France bguery@ 123456invivo.edu
                [†]

                Members listed at end of paper

                Article
                S0140-6736(13)60982-4
                10.1016/S0140-6736(13)60982-4
                7159298
                23727167
                Copyright © 2013 Elsevier Ltd. All rights reserved.

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