MERS-CoV: Multiple Animal–Human Transmissions Detected

Laurie Barclay, MD

September 19, 2013

An analysis of 21 MERS-CoV full genome sequences suggests multiple introductions of the Middle East respiratory syndrome coronavirus (MERS-CoV) from animals to humans, according to the largest genetic analysis of this virus to date, published online September 20 in the Lancet.

"So far, there has been very little information about the molecular evolution of MERS-CoV, and how this relates to virus transmission," senior author Ziad Memish, MD, from the Saudi Arabian Ministry of Health, Riyadh, said in a news release. "While our research substantially adds to the existing evidence base for how, where, and when MERS-CoV is transmitting, further definition of the exposures responsible for the sporadic introductions of MERS-CoV into human populations is urgently needed to provide the necessary information to interrupt transmission and contain the virus."

Since it was first detected in June 2012, MERS-CoV has caused 104 confirmed human infections globally, 49 of which were fatal. Of these infections, 82 cases and 41 deaths were from Saudi Arabia. To elucidate MERS-CoV transmission, evolution, and origin, the investigators performed full-genome deep sequencing on nucleic acid extracted directly from polymerase chain reaction–confirmed clinical samples.

Using these data, the researchers can determine how, when, and where the virus has evolved, including whether human infections resulted from a single or multiple passages from an animal to a human.

The investigators performed phylogenetic analysis of 9 published MERS-CoV genomes and 21 MERS viral genomes obtained from their Riyadh patients, which is the largest number of MERS-CoV genomes described to date. Of the latter group, 13 of 21 had 100%, 4 had 85% to 95%, and 4 had 30% to 50% genome coverage. There were 3 distinct MERS-CoV genotypes.

The circulating MERS-CoV in Saudi Arabia was centered around Riyadh, with sporadic excursions to other centers. The animal reservoir for MERS-CoV appeared to be geographically diverse, according to phylogeographic analyses. Selection analysis showed changes in the S protein and other evidence of accumulation of genetic diversity. Support for transmission of MERS-CoV to humans by an intermediary animal host included the considerable time elapsed since the viruses shared a common ancestor. No animal reservoir was definitively identified, although bats and dromedary camels may be involved.

"Transmission within Saudi Arabia is consistent with either movement of an animal reservoir, animal products, or movement of infected people," the study authors write. "Further definition of the exposures responsible for the sporadic introductions of MERS-CoV into human populations is urgently needed."

In the Al-Hasa cluster, the genetic diversity suggested the possibility of more than 1 virus introduction in the hospital outbreak.

"In lieu of our study's genomic findings, and the fact that the source of the MERS coronavirus has not yet been found, transmission of this virus appears to be more complicated than anticipated," coauthor Alimuddin I. Zumla, MBChB, PhD, from University College London, United Kingdom, said in the news release. "The reassuring news is that two mass gatherings events, attracting over 8 million pilgrims, have occurred in Mecca, Saudi Arabia since the discovery of MERS-CoV 12 months ago...and yet no major outbreaks of MERS-CoV cases have been reported from these events to date. Watchful surveillance and vigilance is required despite the minimal risk of global spread."

In an accompanying comment, David S.C. Hui, MBBS, MD, from the Department of Medicine and Therapeutics, and Stanley Ho Centre for Emerging Infectious Diseases, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China, agree that more research is needed to determine the mode of transmission and exposures resulting in sporadic introductions of MERS-CoV into human populations.

"Development of rapid and reliable diagnostic assays is also urgently needed so that health authorities can take appropriate public health measures to interrupt disease transmission and contain the virus," Dr. Hui and Dr. Ho conclude.

Saudi Arabian Ministry of Health, Wellcome Trust, European Community, and National Institute of Health Research University College London Hospitals Biomedical Research Centre funded this study. The study authors and Dr. Hui have disclosed no relevant financial relationships.

Lancet. Published online September 20, 2013. Abstract

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