Wednesday, May 02, 2018

A Molecular, Serologic & Epidemiologic Investigation Of A Multi-Hospital Oubreak Of MERS-CoV - Jordan


Although Saudi Arabia - with 82% of all known cases - is viewed as the epicenter of the emerging MERS virus, the first known hospital outbreak (retrospectively identified) occurred in neighboring Jordan, in April of 2012 (see Serological Testing Of 2012 Jordanian MERS Outbreak).
While Jordan trails far behind both Saudi Arabia and the UAE in the number of cases, in 2015 they did report a multi-hospital outbreak (see ECDC Rapid Risk Assessment On MERS-CoV & The Jordanian Cluster) involving at least 16 cases. 
Details, at the time, were scant.  The ECDC wrote in October of 2015:
The majority of the reported cases in the current outbreak in Jordan have an exposure history involving a hospital with an admitted confirmed MERS case. The role of hospitals as amplifiers of MERS-CoV infection is now well known. The risk of importation of cases to EU/EEA Member States from Jordan is considered low.
Today, with the publication of a new study in the Open Forum Infectious Diseases, we get a much more detailed look at both the transmission, and evolution, of the MERS virus during this Jordanian cluster.
Not only do we learn that this multi-hospital outbreak involved 9 different facilities - all epidemiologically and serologically linked to a single introduction of the virus in one hospital - we discover the MERS virus itself was a distinct genetic variant.
Although the MERS coronavirus hasn't shown as much genetic diversity as have highly promiscuous influenza viruses - it is far from static - and continues to evolve, mutate, and adapt (see mBio: Origin & Possible Genetic Recombination Of MERS-CoV - China).

The full, open-access, accepted manuscript is available as a PDF file, although it awaits final formating and editing.  You'll want to read it in its entirety, as I've only excerpted the abstract.  I'll have a bit more when you return.

Accepted Manuscript 
Multi-hospital outbreak of a Middle East respiratory syndrome coronavirus deletion variant, Jordan: A molecular, serologic, and epidemiologic investigation

Daniel C Payne Holly M Biggs Mohammad Mousa Al-Abdallat Sultan Alqasrawi Xiaoyan Lu Glen R Abedi Aktham Haddadin Ibrahim Iblan Tarek Alsanouri Mohannad Al Nsour ... Show more

Open Forum Infectious Diseases, ofy095,

An outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) in Jordan in 2015 involved a variant virus that acquired distinctive deletions in the accessory open reading frames. We conducted a molecular and seroepidemiologic investigation to describe the deletion variant’s transmission patterns and epidemiology.
We reviewed epidemiologic and medical chart data and analyzed viral genome sequences from respiratory specimens of MERS-CoV cases. In early 2016, sera and standardized interviews were obtained from MERS-CoV cases and their contacts. Sera were evaluated by nucleocapsid and spike protein enzyme immunoassays and microneutralization.

Among 16 cases, 11 (69%) had healthcare exposure and 5(31%) were relatives of a known case; 13 (81%) were symptomatic and 7(44%) died. Genome sequencing of MERS-CoV from 13 cases revealed 3 transmissible deletions associated with clinical illness during the outbreak. Deletion variant sequences were epidemiologically clustered and linked to a common transmission chain.
Interviews and sera were collected from 2 surviving cases, 23 household contacts, and 278 healthcare contacts; 1( 50%) case, 2( 9%) household contacts, and 3 (1%) healthcare contacts tested seropositive.


The MERS-CoV deletion variants retained human-to-human transmissibility and caused clinical illness in infected persons despite accumulated mutations. Serology suggested limited transmission beyond that detected during the initial outbreak investigation.
        (Continue . . . .)

Given the number of asymptomatic MERS cases that have been reported over the past couple of years - a direct result of increased contact testing following the 2015 WHO Statement On The 10th Meeting Of the IHR Emergency Committee On MERS - it isn't terribly surprising that follow-up serology tests uncovered a limited number of previously unknown infections in this cluster.
Serological testing for previous MERS infection, however, is not as clear cut as one would hope. Mild or asymptomatic cases tend to mount a weak, short term, immune response, and may not test positive within a few months of their illness.
In April of 2016, in EID Journal: Antibody Response & Disease Severity In HCW MERS Survivors, a study tested 9 health care workers who were infected during the 2014 Jeddah outbreak (2 severe pneumonia, 3 milder pneumonia, 1 URTI, and 3 asymptomatic), found only those with severe pneumonia still carried detectable levels of antibodies 18 months later.

A year later (May 2017) a report in the EID Journal: MERS-CoV Antibody Response After 1 Year, followed and tested 11 survivors of South Korea's 2015 MERS outbreak at 6 and 12 months, and like earlier studies, found that those with mild illness saw significant reduction in antibody titers over a year's time.
So the small number of unrecognized cases in this (and other) clusters should be regarded as potentially understated.
Despite the intensive epidemiological and serological investigation, some gaps in how the virus was transmitted in this multi-hospital cluster remain.

At least one seropositive health care worker may have been the link between 2 patient cases, further bolstering the idea that asymptomatic or mildly symptomatic cases may be occasional `silent spreaders' of the virus (see The Lancet Inf. Dis.: MERS-CoV Risk Factors & Determinants Of Primary, Household, & Nosocomial Transmission).
While MERS has been on the back burner the past year or so, with a marked decrease in cases and large hospital clusters, this a reminder that the virus remains a formidable foe, and wouldn't require a great deal of genetic tweaking in order to blow up  into a global threat.
For more, you may wish to revisit:
WHO List Of Blueprint Priority Diseases

Study: A Pandemic Risk Assessment Of MERS-CoV In Saudi Arabia)
Ziad Memish: Two MERS-CoV Hospital Super Spreading Studies
EID Journal: MERS-CoV Transmission in Extended Family, Saudi Arabia, 2014

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