Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study. 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., Rambaut, A., Zumla, A. I., & Memish, Z. A. Lancet (London, England), 382(9909):1993–2002, December, 2013.
doi  abstract   bibtex   
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.
@article{cotten_transmission_2013,
	title = {Transmission and evolution of the {Middle} {East} respiratory syndrome coronavirus in {Saudi} {Arabia}: a descriptive genomic study.},
	volume = {382},
	copyright = {Copyright (c) 2013 Cotten et al. Open Access article distributed under the terms  of CC BY-NC-ND. Published by Elsevier Ltd. All rights reserved.},
	issn = {1474-547X 0140-6736},
	doi = {10.1016/S0140-6736(13)61887-5},
	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.},
	language = {eng},
	number = {9909},
	journal = {Lancet (London, England)},
	author = {Cotten, Matthew and Watson, Simon J. and Kellam, Paul and Al-Rabeeah, Abdullah A. and Makhdoom, Hatem Q. and Assiri, Abdullah and Al-Tawfiq, Jaffar A. and Alhakeem, Rafat F. and Madani, Hossam and AlRabiah, Fahad A. and Al Hajjar, Sami and Al-nassir, Wafa N. and Albarrak, Ali and Flemban, Hesham and Balkhy, Hanan H. and Alsubaie, Sarah and Palser, Anne L. and Gall, Astrid and Bashford-Rogers, Rachael and Rambaut, Andrew and Zumla, Alimuddin I. and Memish, Ziad A.},
	month = dec,
	year = {2013},
	pmid = {24055451},
	pmcid = {PMC3898949},
	keywords = {*Disease Outbreaks, *Evolution, Molecular, *Genome, Viral, Base Sequence, Coronavirus Infections/epidemiology/*genetics/transmission, Coronavirus/*genetics, Gene Amplification, Humans, Respiratory Tract Infections/epidemiology/*genetics/transmission, Saudi Arabia/epidemiology, Syndrome},
	pages = {1993--2002},
}
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