Study suggests multiple MERS-CoV introductions

One of the big mysteries about the Middle East respiratory syndrome coronavirus (MERS-CoV) is whether it jumped from animals to humans just once or has made that jump a number of times. A study released today indicates that the second scenario seems more likely, given the genetic diversity in virus samples from 21 Saudi Arabian patients.

Researchers from Saudi Arabia, the United Kingdom, and the United States sequenced the genomes of the 21 isolates and found too much diversity to support the idea that the virus crossed from animals to humans just once and then traveled from person to person to spark all the other cases, according to their report in The Lancet and related press releases.

The findings also suggest that human-to-human transmission is more complicated than expected and raise the possibility that people with undetected infections are spreading the virus, the authors say.

WHO notes recent cases

In other developments, the World Health Organization (WHO) today recognized 18 MERS cases that have been reported in Saudi Arabia since Sep 1, and the Saudi Ministry of Health (MOH) issued an English-language statement confirming 3 new cases that were first reported yesterday in a machine-translated statement.

The 18 confirmed cases noted by the WHO include 3 deaths. The patients are from Hafar Al-Batin, Medina, and Riyadh and range in age from 3 to 75 years. The agency said the cases were announced by the MOH on Sep 1, 5, 8, 10, and 11.

The cases raise the WHO count for MERS-CoV to 132 cases with 58 deaths. The agency also noted the death on Sep 6 of a MERS patient in Qatar whose case was previously confirmed.

The Saudi MOH statement confirmed what was reported yesterday. The new cases involve:

  • A 75-year-old Saudi woman in Medina who died of her illness; she had had contact with another MERS case-patient
  • A 35-year-old Saudi man in Medina who had contact with another patient and is in a hospital intensive care unit
  • An 83-year-old Saudi man in Riyadh who died

All three patients had chronic diseases, the MOH said. The three cases, which were not included in today’s WHO update, raise Saudi Arabia’s MERS tally to 107 cases with 49 deaths.

Genomic findings

In the Lancet study, the scientists sequenced all or part of the genomes of MERS-CoV isolates from 25 patients. These included 19 who were part of the Al-Ahsa (also spelled Al-Hasa) hospital cluster this past spring, plus 3 from Riyadh and 1 from each of three other locations.

They took 21 of these sequences and aligned them with the nine previously published MERS-CoV sequences as part of their phylogenetic analysis. In other steps, they divided 20 of the Al-Ahsa isolates into pairs, calculated the number of nucleotide differences between them, and compared the numbers with the numbers predicted from the time elapsed between when the samples were collected.

“The most important findings from this study are that at least two distinct lineages were circulating in Riyadh in October 2012, and transmission patterns in the epidemic are consistent with both human-to-human transmission and sporadic zoonotic events,” the report says.

A Riyadh isolate that was collected in February 2013 represented a third distinct genotype, the report states, adding, “In view of the evolutionary rate of the virus it is not expected that a single zoonotic event was the source of the epidemic.”

The scientists say their findings and previous ones show the existence of several other distinct MERS-CoV genotypes, besides those represented by the Riyadh isolates.

The findings, according to a Lancet press release, “clearly show that the circulating virus in Saudi Arabia is centred around Riyadh, with sporadic excursions to other centres, although additional virus genomes will need to be analyzed to more firmly establish the locations involved.”

As for the Al-Ahsa cluster, the authors say epidemiologic studies of the outbreak suggested it involved 13 transmission events, but their genetic analysis supported only eight such events. That suggests that more than one introduction of the virus helped spark the outbreak.

“Our data suggest that local spread of virus in the Al-Hasa outbreak might be more complex than previously thought, with additional sources of the virus contributing to hitherto human-to-human transmission chains,” the report states.

In a press release from the UK’s Wellcome Trust Sanger Institute, coauthor Paul Kellam, PhD, commented, “The genome differences we discovered in some infected people were too great to be explained by replication errors occurring in the virus as it is passed from human to human during a single chain of infection. Instead our findings suggest that different lineages of the virus have originated from the virus jumping across to humans from an animal source a number of times.”

From their genetic data, the authors estimate that MERS-CoV emerged in July 2011, though the emergence could have occurred as early as July 2007.

No animal source for the virus has yet been clearly identified, although related viruses are known to exist in bats; also, camels in Oman, Egypt, and the Canary Islands were recently found to have antibodies to MERS-CoV or a closely related virus. A small fragment of viral material that was found in bat feces in Saudi Arabia was recently reported to match MERS-CoV, but the finding has been controversial.

In an accompanying Lancet commentary, David S. Hui, MBBS, MD, of the Chinese University of Hong Kong writes, “The current genome sequence set is not adequate to discriminate definitively between single or multiple zoonotic introductions [of MERS-CoV], but the description of the pair of related genomes from Riyadh and Bisha and the description of cases in east and west Saudi Arabia in both major lineages of the tree suggest many zoonotic events.”

“Although this report provides neither direct evidence of animal transmission nor the precise mechanism of transmission, the information is useful in tracing the source and transmission of MERS-CoV,” Hui adds.

Environmental stability of MERS-CoV

In another MERS-CoV development today, researchers who tested the virus’s ability to survive in different environmental conditions reported that it and the SARS (severe acute respiratory syndrome) virus had similar stability profiles and that the new virus can survive longer than the 2009 H1N1 flu virus. The team from the National Institute of Allergy and Infectious Diseases (NIAID) pathogen lab in Hamilton, Mont., reported their findings in Eurosurveillance.

Using virus grown from MERS-CoV samples provided by Erasmus University, they found that it was more stable than 2009 H1N1 under low temperature and low humidity conditions and could still be recovered after 48 hours. The researchers said the findings suggest the virus can be transmitted by contact or fomites.

They also found that MERS-CoV can remain viable in an airborne state, which suggests that it could gain the ability for aerosol spread. Prolonged survival of the virus on surfaces increases the likelihood that it spreads by contact or fomites, the scientists reported.

They noted, however, that the drop in viability they saw at high temperatures suggests that, in the Arabian Peninsula, direct contact rather than fomite transmission is the most likely route of zoonotic and human-to-human transmission in outdoor settings.

News reporter Lisa Schnirring contributed to this article.

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 (published online Sep 20) [Abstract]

Hui DS. Tracking the transmission and evolution of MERS-CoV. (Commentary) Lancet 2013 (published online Sep 20) [Extract]

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