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Since mid-March 2014, the frequency with which cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection have been reported has increased, with the majority of recent cases reported from Saudi Arabia and United Arab Emirates (UAE).

In addition, the frequency with which travel-associated MERS cases have been reported and the number of countries that have reported them to the World Health Organization (WHO) have also increased. The first case of MERS in the United States, identified in a traveler recently returned from Saudi Arabia, was reported to CDC by the Indiana State Department of Health on May 1, 2014, and confirmed by CDC on May 2. A second imported case of MERS in the United States, identified in a traveler from Saudi Arabia having no connection with the first case, was reported to CDC by the Florida Department of Health on May 11, 2014. The purpose of this report is to alert clinicians, health officials, and others to increase awareness of the need to consider MERS-CoV infection in persons who have recently traveled from countries in or near the Arabian Peninsula.

This report summarizes recent epidemiologic information, provides preliminary descriptions of the cases reported from Indiana and Florida, and updates CDC guidance about patient evaluation, home care and isolation, specimen collection, and travel as of May 13, 2014.

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In April 2012, the Jordan Ministry of Health (JMoH) investigated an outbreak of lower respiratory illnesses at a hospital in Jordan; two fatal cases were retrospectively confirmed by rRT-PCR to be the first detected cases of Middle East Respiratory Syndrome (MERS-CoV).

METHODS:  Epidemiologic and clinical characteristics of selected potential cases were assessed through serum blood specimens, medical chart reviews and interviews with surviving outbreak members, household contacts, and healthcare personnel. Cases of MERS-CoV infection were identified using three U.S. Centers for Disease Control and Prevention (CDC) serologic tests for detection of anti-MERS-CoV antibodies.

RESULTS:  Specimens and interviews were obtained from 124 subjects. Seven previously unconfirmed individuals tested positive for anti-MERS-CoV antibodies by at least two of three serologic tests, in addition to two fatal cases identified by rRT-PCR. The case fatality rate among the nine total cases was 22%. Six cases were healthcare workers at the outbreak hospital, yielding an attack rate of 10% among potentially exposed outbreak hospital personnel. There was no evidence of MERS-CoV transmission at two transfer hospitals having acceptable infection control practices.

CONCLUSION:  Novel serological tests allowed for the detection of otherwise unrecognized cases of MERS-CoV infection among contacts of a Jordan hospital-associated respiratory illness outbreak in April 2012, resulting in a total of nine test-positive cases. Serologic results suggest that further spread of this outbreak to transfer hospitals did not occur. Most cases had no major, underlying medical conditions; none were on hemodialysis. Our observed case fatality was lower than has been reported from outbreaks elsewhere.

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Analysis of clinical samples of patients with new viral infections is critical to confirm the diagnosis, provide viral load and sequence data necessary for characterizing viral kinetics, transmission and evolution of the virus. We analysed samples from 112 patients infected with the recently discovered Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

METHODS:  Respiratory tract samples from MERS-CoV PCR-confirmed cases were analysed for yields of MERS-CoV viral load and fraction of MERS-CoV genome. These values were analyzed to determine associations with clinical sample type.

RESULTS:  Samples from 112 MERS-CoV PCR-positive individuals were analysed: 13 Sputum samples, 64 Nasopharyngeal swabs, 30 Tracheal aspirates, 3 Broncho-alveolar lavages and 2 were of unknown origin. Tracheal aspirates yielded significantly higher MERS-CoV high viral load when compared with Nasopharyngeal swabs (p=0.005) and to Sputum (p=0.0001). Tracheal aspirates had similar viral load compared to Broncho-alveolar lavage (p=0.3079). Broncho-alveolar lavage samples and tracheal aspirates had significantly higher vital load values than nasopharyngeal swabs (p=0.0095 and p=0.0002) and Sputum samples (p=0.0009 and p=0.0001). The genome yield from tracheal aspirates and bronchoalveolar lavage samples were similar (p=0.1174).

CONCLUSIONS:  Lower respiratory tract samples yield significantly higher MERS-CoV viral load, and genome fractions than upper respiratory tract samples.

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Coronaviruses comprise a large group of emergent human and animal pathogens, including the highly pathogenic SARS-CoV and MERS-CoV strains that cause significant morbidity and mortality in infected individuals, especially the elderly.

As emergent viruses may cause episodic outbreaks of disease over time, human samples are limited. Systems biology and genetic technologies maximize opportunities for identifying critical host and viral genetic factors that regulate susceptibility and virus-induced disease severity. These approaches provide discovery platforms that highlight and allow targeted confirmation of critical targets for prophylactics and therapeutics, especially critical in an outbreak setting. Although poorly understood, it has long been recognized that host regulation of virus-associated disease severity is multigenic. The advent of systems genetic and biology resources provides new opportunities for deconvoluting the complex genetic interactions and expression networks that regulate pathogenic or protective host response patterns following virus infection.

Using SARS-CoV as a model, dynamic transcriptional network changes and disease-associated phenotypes have been identified in different genetic backgrounds, leading to the promise of population-wide discovery of the underpinnings of Coronavirus pathogenesis.

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