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

Benoit Guery, Julien Poissy, Loubna el Mansouf, Caroline Séjourné, Nicolas Ettahar, Xavier Lemaire, Fanny Vuotto, Anne Goffard, Sylvie Behillil, Vincent Enouf, Valérie Caro, Alexandra Mailles, Didier Che, Jean-Claude Manuguerra, Daniel Mathieu, Arnaud Fontanet, Sylvie van der Werf, MERS-CoV study group, D Caparros, L Vrigneaud, D Labatut, T Quemeneur, A-A Cracco, A Guaguere, C Rousselin, E Lefebvre, P Morel, B Kowalski, T Coppin, K Faure, E Senneville, H Melliez, R Joly, P Goldstein, A Vincentelli, N Rousse, R Favory, A Palud, E Parmentier-Decrucq, M Kauv, M Benassaya, D Briand, M Lazzerini, C Socratous, F Fichenick, J Riou, K Blanckaert, P Chaud, M-C Paty, J-P Legendre, S Segovia-Kueny, Benoit Guery, Julien Poissy, Loubna el Mansouf, Caroline Séjourné, Nicolas Ettahar, Xavier Lemaire, Fanny Vuotto, Anne Goffard, Sylvie Behillil, Vincent Enouf, Valérie Caro, Alexandra Mailles, Didier Che, Jean-Claude Manuguerra, Daniel Mathieu, Arnaud Fontanet, Sylvie van der Werf, MERS-CoV study group, D Caparros, L Vrigneaud, D Labatut, T Quemeneur, A-A Cracco, A Guaguere, C Rousselin, E Lefebvre, P Morel, B Kowalski, T Coppin, K Faure, E Senneville, H Melliez, R Joly, P Goldstein, A Vincentelli, N Rousse, R Favory, A Palud, E Parmentier-Decrucq, M Kauv, M Benassaya, D Briand, M Lazzerini, C Socratous, F Fichenick, J Riou, K Blanckaert, P Chaud, M-C Paty, J-P Legendre, S Segovia-Kueny

Abstract

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.

Copyright © 2013 Elsevier Ltd. All rights reserved.

Figures

Figure 1
Figure 1
Radiographs and CT scans of the chest of patient 1 (A) CT scans of the chest obtained on April 24. Substantial bilateral ground-glass opacity and consolidation can be seen. (B, C) Chest radiographs. Groundglass opacity and condensation, mainly on the lower right lobe, were noted on April 30 (B). Bilateral ground-glass opacity and consolidation were noted on May 8 (C). (D) On May 17, the CT scan of the chest showed a bilateral consolidation of the lung.
Figure 2
Figure 2
Radiographs of the chest of patient 2 (A) Chest radiograph obtained on May 9 showed a systematic consolidation of the upper right lung lobe. (B) On May 12, ground-glass opacity and consolidation could also be seen in the lower left lobe. Bilateral ground-glass opacities and consolidation were noted afterwards on May 15 (C) and May 17 (D).
Figure 3
Figure 3
Timeline of pertinent exposure, dates of illness, and virological findings in patients 1 and 2 Exposure (bold red line) shows the period during which the two patients shared the same room. BAL=bronchoalveolar lavage. NP=nasopharyngeal swab. SP=sputum. Inc=Inconclusive. ECMO=extracorporeal membrane oxygenation. ICU=intensive-care unit.

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