New study of MERS virus sequences supports idea of multiple jumps into people

TORONTO – The spread of MERS in Saudi Arabia is caused by a mixture of person-to-person and animal-to-person transmission, authors of a new study on the virus suggest.

The work is based on an analysis of genetic sequences from 21 MERS patients from that country. It is the largest collection of MERS genetic blueprints published to date, and swells the number of publicly available sequences to 30.

“Transmission within Saudi Arabia is consistent with either movement of an animal reservoir, animal products, or movement of infected people,” the authors conclude.

“Further definition of the exposures responsible for the sporadic introductions of MERS-CoV” – short for coronavirus – “into human populations is urgently needed to provide the necessary information to interrupt transmission and contain the virus.”

That statement, which concludes the study, echoes pleas from outside experts and the World Health Organization that Saudi officials undertake what is known as a case control study, which is an essential tool for trying to crack the mystery of how people are becoming infected with MERS.

Though the new coronavirus has now been on the world’s radar for a year, to date there has been no case control study on MERS patients published, and it is unclear if one has even been started.

Friday marks one year since news of the new virus was first published by the online infectious diseases monitoring service ProMED, with the report of a man from the Saudi city of Bisha who died from the infection in June, 2012. As of Thursday, the global count has grown to 132 confirmed cases; 58 of those infections were fatal.

Next week a panel of experts first struck by the World Health Organization in July to assess the MERS outbreak will reconvene to review the situation.

Dr. Tony Mounts, the agency’s point person for MERS, said the Emergency Committee meeting is not a sign that the WHO believes the outbreak has reached a new level. When the group met in July, it recommended that the WHO reconvene the panel from time to time – and in particular, ahead of next month’s massive Hajj pilgrimage in Saudi Arabia – to keep the panel abreast of the situation.

“It’s just a routine follow-up meeting,” Mounts said.

The MERS sequencing paper is published in the journal The Lancet by a team of researchers from Britain’s Sanger Institute – which applied state of the art techniques to come up with the sequences – as well as others from Britain, the United States and Saudi Arabia.

The senior author of the paper is Dr. Ziad Memish, the Saudi deputy minister of health.

But a number of scientists who reviewed the study – including a coronavirus expert who believes person-to-person spread is now driving the outbreak – say the sequences cannot reveal whether animal-to-human spread is happening. So far the virus has not been found in animals, so there are no animal viruses with which to compare the human sequences.

“What you can say is: These viruses are introduced viruses, but you cannot say from where they were introduced. Either from other humans, in the next village, or from a camel or a cow. This is all possible. We don’t know where they come from,” said Dr. Christian Drosten, director of the institute of virology at the University of Bonn Medical Centre in Bonn, Germany.

It is suspected camels may play a role in the spread of MERS; dromedaries in Oman, Sudan and the Canary Islands have been shown to have antibodies to a MERS-like virus. To date there has been no suggestion cows are part of the MERS picture.

Drosten’s belief the virus is now spreading person to person is not universally shared. But a number of other experts agreed study of the sequences doesn’t reveal their sources.

“The sequence information tells us that there are different coronaviruses causing disease but we still don’t know where the reservoir is,” said Eric Donaldson, a coronavirus expert and an adjunct assistant professor at the University of North Carolina.

The Lancet study also said analysis of the sequences supports previous claims that the virus has probably been spreading since the midway through 2011, about eight months before the first known human cases occurred. Those infections – a cluster of cases in a hospital in Jordan – were recognized as being caused by MERS only after the fact.

While scientists welcomed the release of the data and praised the science behind the analysis, some raised questions about two of the viruses in the series.

The first sequenced MERS virus came from the man from Bisha; it was sequenced at Erasmus Medical Centre in Rotterdam, the Netherlands. But the Lancet analysis contains a second viral genome reportedly from the same man that was sequenced by scientists at the Sanger Institute.

The two sequences are not identical – in fact, there are 98 point mutations between them. Drosten and others question how the two sequences could be so different, saying the man was either infected with two MERS viruses at once – which, they say, is unlikely – or they are viruses from two different people.

The explanation in the paper – that the differences are due to “passaging” the virus in cell culture – doesn’t add up, Drosten said, suggesting there are too many mutations for that to be the case.

“They are definitely two different viruses. One of them is wrong,” said Drosten, who noted he had also sequenced the virus the Erasmus team worked on, and his data match theirs.

Paul Kellam, the virus genomics team leader at the Sanger Institute and one of the authors of the Lancet paper, said he cannot explain the differences.

“We are sure of the provenance of our sample. And I’m sure that the EMC and Rotterdam group are sure of the provenance of their sample,” Kellam said.

“The most important thing is regardless of the provenance of … (the two viruses) the interpretation and the analysis of the entire set of genomes … doesn’t change any of the conclusions of the manuscript.”

Kellam noted that the viruses his group sequenced were from cases that occurred in the spring of this year, comparing them to viruses sequenced earlier. Viruses from infections that have occurred since the beginning of July are not factored into this analysis, he said. As such, the analysis can’t be used to say what is happening with MERS now.

Since early July there have been 53 additional MERS cases and 16 deaths reported. Not all were from Saudi Arabia, but the country has had the bulk of MERS cases.