SummaryBackgroundSince June, 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has, worldwide, caused 104 infections in people including 49 deaths, with 82 cases and 41 deaths reported from Saudi Arabia. In addition to confirming diagnosis, we generated the MERS-CoV genomic sequences obtained directly from patient samples to provide important information on MERS-CoV transmission, evolution, and origin.MethodsFull genome deep sequencing was done on nucleic acid extracted directly from PCR-confirmed clinical samples. Viral genomes were obtained from 21 MERS cases of which 13 had 100%, four 85–95%, and four 30–50% genome coverage. Phylogenetic analysis of the 21 sequences, combined with nine published MERS-CoV genomes, was done.FindingsThree distinct MERS-CoV genotypes were identified in Riyadh. Phylogeographic analyses suggest the MERS-CoV zoonotic reservoir is geographically disperse. Selection analysis of the MERS-CoV genomes reveals the expected accumulation of genetic diversity including changes in the S protein. The genetic diversity in the Al-Hasa cluster suggests that the hospital outbreak might have had more than one virus introduction.InterpretationWe present the largest number of MERS-CoV genomes (21) described so far. MERS-CoV full genome sequences provide greater detail in tracking transmission. Multiple introductions of MERS-CoV are identified and suggest lower R0 values. Transmission within Saudi Arabia is consistent with either movement of an animal reservoir, animal products, or movement of infected people. Further definition of the exposures responsible for the sporadic introductions of MERS-CoV into human populations is urgently needed.FundingSaudi Arabian Ministry of Health, Wellcome Trust, European Community, and National Institute of Health Research University College London Hospitals Biomedical Research Centre.

The Middle East respiratory syndrome coronavirus (MERS-CoV) was first documented in the Kingdom of Saudi Arabia (KSA) in 2012 and, to date, has been identified in 180 cases with 43% mortality. In this study, we have determined the MERS-CoV evolutionary rate, documented genetic variants of the virus and their distribution throughout the Arabian peninsula, and identified the genome positions under positive selection, important features for monitoring adaptation of MERS-CoV to human transmission and for identifying the source of infections. Respiratory samples from confirmed KSA MERS cases from May to September 2013 were subjected to whole-genome deep sequencing, and 32 complete or partial sequences (20 were ≥99% complete, 7 were 50 to 94% complete, and 5 were 27 to 50% complete) were obtained, bringing the total available MERS-CoV genomic sequences to 65. An evolutionary rate of 1.12 × 10−3 substitutions per site per year (95% credible interval [95% CI], 8.76 × 10−4; 1.37 × 10−3) was estimated, bringing the time to most recent common ancestor to March 2012 (95% CI, December 2011; June 2012). Only one MERS-CoV codon, spike 1020, located in a domain required for cell entry, is under strong positive selection. Four KSA MERS-CoV phylogenetic clades were found, with 3 clades apparently no longer contributing to current cases. The size of the population infected with MERS-CoV showed a gradual increase to June 2013, followed by a decline, possibly due to increased surveillance and infection control measures combined with a basic reproduction number (R0) for the virus that is less than 1.

The Saudi Arabian Ministry of Health implemented a pro-active surveillance programme for Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV). We report MERS-CoV data from 5065 Kingdom of Saudi Arabia individuals who were screened for MERS-CoV over a 12-month period. From 1 October 2012 to 30 September 2013, demographic and clinical data were prospectively collected from all laboratory forms received at the Saudi Arabian Virology reference laboratory. Data were analysed by referral type, age, gender, and MERS-CoV real-time PCR test results. Five thousand and 65 individuals were screened for MER-CoV: hospitalized patients with suspected MERS-CoV infection (n = 2908, 57.4%), healthcare worker (HCW) contacts (n = 1695; 33.5%), and family contacts of laboratory-confirmed MERS cases (n = 462; 9.1%). Eleven per cent of persons tested were children (<17 years of age). There were 108 cases (99 adults and nine children) of MERS-CoV infection detected during the 12-month period (108/5065, 2% case detection rate). Of 108 cases, 45 were females (six children and 39 adults) and 63 were males (three children and 60 adults). Of the 99 adults with MERS-CoV infection, 70 were hospitalized patients, 19 were HCW contacts, and ten were family contacts. There were no significant increases in MERS-CoV detection rates over the 12-month period: 2.6% (19/731) in July 2013, 1.7% (19/1100) in August 2013, and 1.69% (21/1238) in September 2013. Male patients had a significantly higher MERS-CoV infection rate (63/2318, 2.7%) than females (45/2747, 1.6%) (p 0.013). MERS-CoV rates remain at low levels, with no significant increase over time. Pro-active surveillance for MERS-CoV in newly diagnosed patients and their contacts will continue.

MERS-CoV disease is not limited to adults. Most cases of childhood MERS-CoV infection were asymptomatic and tested positive during contact investigation of older patients. Severe disease can occur in children with underlying conditions.

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