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Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study.
Lancet. 2013 Dec 14; 382(9909):1993-2002.Lct

Abstract

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.

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Authors+Show Affiliations

Cotten M
Wellcome Trust Sanger Institute, Hinxton, UK.
Watson SJ
Wellcome Trust Sanger Institute, Hinxton, UK.
Kellam P
Wellcome Trust Sanger Institute, Hinxton, UK; Division of Infection and Immunity, University College London, London, UK.
Al-Rabeeah AA
Global Centre for Mass Gatherings Medicine, Ministry of Health, Riyadh, Saudi Arabia.
Makhdoom HQ
Jeddah Regional Laboratory, Ministry of Health, Jeddah, Saudi Arabia.
Assiri A
Global Centre for Mass Gatherings Medicine, Ministry of Health, Riyadh, Saudi Arabia.
Al-Tawfiq JA
Saudi Aramco Medical Services Organisation, Saudi Aramco, Dhahran, Saudi Arabia.
Alhakeem RF
Global Centre for Mass Gatherings Medicine, Ministry of Health, Riyadh, Saudi Arabia.
Madani H
Jeddah Regional Laboratory, Ministry of Health, Jeddah, Saudi Arabia.
AlRabiah FA
King Faisal Specialist Hospital, Riyadh, Saudi Arabia.
Al Hajjar S
King Faisal Specialist Hospital, Riyadh, Saudi Arabia.
Al-nassir WN
Imam Abdulrahman Bin Mohamed Hospital-National Guard Health Affairs-Dammam, Saudi Arabia.
Albarrak A
Prince Sultan Military Medical City, Riyadh, Saudi Arabia.
Flemban H
Alhada Military Hospital, Riyadh, Saudi Arabia.
Balkhy HH
King Abdulaziz Medical City, Riyadh, Saudi Arabia.
Alsubaie S
Paediatric Infectious Diseases, King Saud University, Saudi Arabia.
Palser AL
Wellcome Trust Sanger Institute, Hinxton, UK.
Gall A
Wellcome Trust Sanger Institute, Hinxton, UK.
Bashford-Rogers R
Wellcome Trust Sanger Institute, Hinxton, UK.
Rambaut A
Institute of Evolutionary Biology, Ashworth Laboratories, Kings Buildings, West Mains Road, Edinburgh, UK; Fogarty International Center, NIH, Bethesda, MD, USA.
Zumla AI
Global Centre for Mass Gatherings Medicine, Ministry of Health, Riyadh, Saudi Arabia; Division of Infection and Immunity, University College London, London, UK; UCL Hospitals NHS Foundation Trust, London, UK.
Memish ZA
Global Centre for Mass Gatherings Medicine, Ministry of Health, Riyadh, Saudi Arabia. Electronic address: zmemish@yahoo.com.

MeSH

Base SequenceCoronavirusCoronavirus InfectionsDisease OutbreaksEvolution, MolecularGene AmplificationGenome, ViralHumansRespiratory Tract InfectionsSaudi ArabiaSyndrome

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24055451

Citation

Cotten, Matthew, et al. "Transmission and Evolution of the Middle East Respiratory Syndrome Coronavirus in Saudi Arabia: a Descriptive Genomic Study." Lancet (London, England), vol. 382, no. 9909, 2013, pp. 1993-2002.
Cotten M, Watson SJ, Kellam P, et al. Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study. Lancet. 2013;382(9909):1993-2002.
Cotten, M., Watson, S. J., Kellam, P., Al-Rabeeah, A. A., Makhdoom, H. Q., Assiri, A., Al-Tawfiq, J. A., Alhakeem, R. F., Madani, H., AlRabiah, F. A., Al Hajjar, S., Al-nassir, W. N., Albarrak, A., Flemban, H., Balkhy, H. H., Alsubaie, S., Palser, A. L., Gall, A., Bashford-Rogers, R., ... Memish, Z. A. (2013). Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study. Lancet (London, England), 382(9909), 1993-2002. https://doi.org/10.1016/S0140-6736(13)61887-5
Cotten M, et al. Transmission and Evolution of the Middle East Respiratory Syndrome Coronavirus in Saudi Arabia: a Descriptive Genomic Study. Lancet. 2013 Dec 14;382(9909):1993-2002. PubMed PMID: 24055451.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study. AU - Cotten,Matthew, AU - Watson,Simon J, AU - Kellam,Paul, AU - Al-Rabeeah,Abdullah A, AU - Makhdoom,Hatem Q, AU - Assiri,Abdullah, AU - Al-Tawfiq,Jaffar A, AU - Alhakeem,Rafat F, AU - Madani,Hossam, AU - AlRabiah,Fahad A, AU - Al Hajjar,Sami, AU - Al-nassir,Wafa N, AU - Albarrak,Ali, AU - Flemban,Hesham, AU - Balkhy,Hanan H, AU - Alsubaie,Sarah, AU - Palser,Anne L, AU - Gall,Astrid, AU - Bashford-Rogers,Rachael, AU - Rambaut,Andrew, AU - Zumla,Alimuddin I, AU - Memish,Ziad A, Y1 - 2013/09/20/ PY - 2013/9/24/entrez PY - 2013/9/24/pubmed PY - 2013/12/27/medline SP - 1993 EP - 2002 JF - Lancet (London, England) JO - Lancet VL - 382 IS - 9909 N2 - 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. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/24055451/Transmission_and_evolution_of_the_Middle_East_respiratory_syndrome_coronavirus_in_Saudi_Arabia:_a_descriptive_genomic_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0140-6736(13)61887-5 DB - PRIME DP - Unbound Medicine ER -