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MERS and SARS Similarities Increase
Recombinomics Commentary 18:00
November 28, 2013

The critical remaining question about this virus is the route by which humans are infected. A large portion of the human cases that did not have an apparent human source of their infection, also did not have direct camel exposure. Specifically, the remaining questions include 1) the specific behaviors and exposures that bring humans into contact with sources of the virus, 2) whether camels are a part of the chain of transmission to humans or whether they are coincidentally infected, and 3) whether other animals may also play a role in transmission or act as a reservoir.

The above comments from the November 22 WHO update once again invites comparisons between MERS and SARS.  MERS is looking increasingly like a slowly emerging SARS outbreak based on epidemiological and sequence data.  The media reports citing the announcement of sequence data this week from a case (43M) and camel in Jeddah, Saudi Arabia, as well as PCR and sequence confirmation in 3 asymptomatic camels linked to two confirmed cases in Qatar raises the strong possibilities that more similarities between MERS and SARS will emerge soon.

The first confirmed cases of SARS were in late 2002 (samples confirmed in 2003).  These early cases were in Guangdong province (population almost 100 million).  However, super spreader events (SSE) were reported in the city of Guangzhou (population almost 10 million) in early 2003, with reported cases increasing to 50 per day peaking in early February.  A nephrologist, who had treated patients Guangzhou, traveled to Hong Kong for a wedding and checked into room 911 in the Metropole Hotel (Hotel M) on February 21.  An SEE occurred on the 9th floor leading to the infection of multiple guests, who subsequently traveled to Vietnam, Singapore, Canada and the United States, which was followed by SSEs in Vietnam, Singapore, Canada, and Hong Kong (linked to former guests of hotel M).

The number of reported cases increased dramatically in March and April, but quickly declined in May.  Intermediate hosts were identified in live markets in Shenzhen, and sequences were closely related to the initial cases in Guangdong Province. However, sequences from cases in Guangzhou and Hotel M had a 29 BP deletion, which was present in the vast majority of subsequent sequences.  Moreover, this deletion (as well as larger deletions found in human clusters), where not detected in animal sequences.

There was extensive culling and such animals (most notably masked palm civets, aka civet cats) were banned.  However, after the lifting of the ban in the fall of 2003, SARS-CoV was again detected in live markets.  This later version also lacked the deletions found in the prior cases, but was easily distinguished from the sequences from isolates in late 2002 and early 2003.  Moreover, human cases were subsequently found in late 2003, which matched these more evolved sequences.  The sequences in the human isolates led to massive culling in Hong Kong and subsequent human cases were not detected.  However, testing of animals in farms supplying the live markets failed to detect SARS-CoV, so the source of these later sequences remains unclear.

A subsequent search for a natural host for SARS-CoV focused on bats, and although SARS-like CoVs were identified, these sequences were decades or centuries away from the human / live market sequences.  The search noted that many different coronavirus were hosted by bats, including beta coronavirus that were similar to OC43 (a human cold virus serving as the prototype for 2a), SARS-CoV, representing 2b, as well as additional sequences representing 2c and 2d.

The universal probes used to identify these various bat coronavirus were also used to identify MERS-CoV in the first two confirmed cases, which were most closely related to the bat beta2c sequences.  The initial bat beta2c sequences were from Guangdong and were centuries away from the MERS-CoV sequences.  However, testing of bat sequences from Europe and Africa identified more closely related beta 2c sequences which were more closely related to MERS-CoV, but these sequences were still decades or centuries away from the human sequences. 

However, a short (203 BP) sequence from a bat in Bisha exactly match one of the sequences from the first confirmed MERS case (who lived in Bisha but was diagnosed and died in Jeddah).  Thus, this sequence was more closely related to the human EMC sequence than any other human MERS sequence.  However, the species harboring this bat sequence had a very limited geographic reach in Saudi Arabia (and was more widespread in India, Sudan and Egypt).

Testing in camels suggested MERS-CoV may be widespread in the Middle East and northeastern Africa.  Beta 2c antibodies where detected at high frequencies and titers in racing camels in Oman.  Similar results were also reported for camels imported to Egypt from Sudan for slaughter.

The strongest data hover comes from recent PCR results (and associated sequence data) for a symptomatic camel in Jeddah (owned by a confirmed critical MERS case, 43M) and three asymptomatic camels in Qatar (owner or linked to two recovered cases, 61M and 23M).
The latest camel data has much in common with live animals in Guangdong Province or Hong Kong linked to SARS cases in 2002 and 2003.  As was seen for recent MERS cases (which are significantly more commonly reported inside and outside the Middle East in 2013 than 2012), most cases are not linked to animal sources and super spreader events have produce nosocomial outbreaks in Jordan and Saudi Arabia, the animal links may spark outbreaks.

However, elimination of an animal source for MERS may be significantly more difficult than for SARS.

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