Published Online May 29, 2013
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, and
the MERS-CoV study group*
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
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.
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.
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
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
Whereas an as yet unidentified animal reservoir might
have caused the initial outbreaks by introducing the virus
into the human population, the occurrence of clusters,
whether in the community or in hospitals, is a worrying
development, because it might result from adaptation of
the virus to inter-human transmission. This process of
adaptation might have been pivotal in the switch from
aborted outbreaks to the international pandemic of
SARS-CoV in 2003–04.
We report detailed clinical and virological information for two related cases of MERS-CoV
disease, after nosocomial transmission of the virus from one patient to another in a French hospital in April, 2013
Patient 1 was transferred to the Douai hospital
intensive-care unit (ICU) on April 29, where non-invasive
mechanical ventilation was started, and antimicrobial
therapy was modified to piperacilline plus tazobactam
and linezolid. He had rapid respiratory deterioration, and
was intubated on April 30 (figure 1B). Respiratory failure
was followed by shock and renal failure, leading to
noradrenaline administration and continuous veno
- venous haemofiltration.
On May 1, on the basis of the clinical presentation and
the history of recent travel to Dubai, the hypothesis of an
infection with MRES-CoV was raised, prompting the
transfer of nasopharyngeal and stored bronchoalveolar
lavage samples to the National Reference Center in Paris.
Further worsening of the respiratory status with a
partial pressure of oxygen (PaO
to fraction of inspired
) ratio of 1 despite low tidal volume and high-
positive end expiratory pressure (PEEP) ventilation,
inhaled nitric oxide, prone positioning, sedation, and
neuromuscular blockade, prompted the implementation
of extracorporeal membrane oxygenation (ECMO).
Persisting haemodynamic support with norepinephrine
at 0·5 mg/h was necessary. The patient was transferred to
the ECMO referral centre ICU of Lille University
Teaching Hospital on May 8 (figure 1C). As of May 27, the
patient remained under ECMO therapy because of
persisting severe acute respiratory distress syndrome
(figure 1D). At 100% FiO
on both ECMO and ventilatorsettings . . .
Chart on pg. 6/8
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