Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study

Matthew Cotten PhD b †, Simon J Watson PhD b †, Prof Paul Kellam PhD b m †, Abdullah A Al-Rabeeah FRCS a, Hatem Q MakhdoomPhD c, Abdullah Assiri MD a, Jaffar A Al-Tawfiq MD d, Rafat F Alhakeem MD a, Hossam Madani PhD c, Fahad A AlRabiah MD g,Sami Al Hajjar MD g, Wafa N Al-nassir MD h, Ali Albarrak MD i, Hesham Flemban MD j, Hanan H Balkhy MD k, Sarah Alsubaie MD l,Anne L Palser PhD b, Astrid Gall Dr Med Vet b, Rachael Bashford-Rogers MChem b, Prof Andrew Rambaut Prof e f, Prof Alimuddin I Zumla FRCP a m n †, Prof Ziad A Memish FRCP a

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Summary

Background

Since 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.

Methods

Full 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.

Findings

Three 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.

Interpretation

We 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.

Funding

Saudi Arabian Ministry of Health, Wellcome Trust, European Community, and National Institute of Health Research University College London Hospitals Biomedical Research Centre.