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Review
. 2015 Apr 16:202:60-88.
doi: 10.1016/j.virusres.2015.01.021. Epub 2015 Feb 2.

Middle East respiratory syndrome: An emerging coronavirus infection tracked by the crowd

Ian M Mackay  1 , Katherine E Arden  2
Affiliations
Review

Middle East respiratory syndrome: An emerging coronavirus infection tracked by the crowd

Ian M Mackay et al. Virus Res. .

Abstract

In 2012 in Jordan, infection by a novel coronavirus (CoV) caused the first known cases of Middle East respiratory syndrome (MERS). MERS-CoV sequences have since been found in a bat and the virus appears to be enzootic among dromedary camels across the Arabian Peninsula and in parts of Africa. The majority of human cases have occurred in the Kingdom of Saudi Arabia (KSA). In humans, the etiologic agent, MERS-CoV, has been detected in severe, mild and influenza-like illness and in those without any obvious signs or symptoms of disease. MERS is often a lower respiratory tract disease associated with fever, cough, breathing difficulties, pneumonia that can progress to acute respiratory distress syndrome, multiorgan failure and death among more than a third of those infected. Severe disease is usually found in older males and comorbidities are frequently present in cases of MERS. Compared to SARS, MERS progresses more rapidly to respiratory failure and acute kidney injury, is more often observed as severe disease in patients with underlying illnesses and is more often fatal. MERS-CoV has a broader tropism than SARS-CoV, rapidly triggers cellular damage, employs a different receptor and induces a delayed proinflammatory response in cells. Most human cases have been linked to lapses in infection prevention and control in healthcare settings, with a fifth of virus detections reported among healthcare workers. This review sets out what is currently known about MERS and the MERS-CoV, summarises the new phenomenon of crowd-sourced epidemiology and lists some of the many questions that remain unanswered, nearly three years after the first reported case.

Keywords: Camel; Emerging infectious disease; Healthcare worker; MERS; MERS-CoV; Zoonosis.

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Figures

Fig. 1
Fig. 1
A timeline of key scientific milestones, cases of interest and mass gatherings of relevance to the potential spread of MERS-CoV among humans and from animals to humans. A yellow circle indicates when a country reported a laboratory confirmed detection and an orange circle denotes ensuing local transmission. Mention of DC contact prior to disease is marked by a black camel icon.
Fig. 2
Fig. 2
The 23 countries in which MERS-CoV has been identified and a guide as to the number of cases at each location. Local transmission is highlighted (blue star) as are countries with DCs that contain antibodies reactive with MERS-CoV, viral RNA or infectious virus (camel icon). Correct as of the 20th January, 2015.
Fig. 3
Fig. 3
Schematic of MERS-CoV genome (EMC/2012 variant isolated from sputum of a 60-year old man from Bisha, KSA). Open reading frames are indicated as yellow rectangles bracketed by terminal untranslated regions (UTR; grey rectangles). The 5′UTR includes the predicted leader (L) transcription-regulatory sequence. FS-frame-shift. Predicted papain-like proteinase cleavage sites are indicated with orange arrows resulting in ∼16 cleavage non-structural protein products (based on (van Boheemen et al., 2012)). The genome is drawn to scale using Geneious v6.1.6 and annotated using Adobe Illustrator. MERS-CoV EMC/2012 sequence GenBank accession number JX869059 (Zaki et al., 2012).
Fig. 4
Fig. 4
The genetic relationship between all near-complete and complete MERS-CoV genome nucleotide sequences (downloaded from GenBank using the listed accession numbers; England2 was obtained from http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/MERSCoV/respPartialgeneticsequenceofnovelcoronavirus/%5D). This neighbour joining tree was created in MEGA v6 using an alignment of human and DC-derived MERS-CoV sequences (Geneious v6). The tree was rooted using NRCE-HKU205 CAMEL KJ477102. Clades are indicated next to dark (Clade A) or pale (Clade B) blue vertical bars. Camel icons denote genomes from DC. MERS-CoV sequences described as originating from the same patient either before (Bisha_1) or after (EMC/2012) passage in cell culture (Cotten et al., 2013b) are starred (red). Identical genomes from a human and one of his ill camels from Jeddah (Azhar et al., 2014a), the KSA are also starred (yellow). Healthcare or community outbreaks are boxed (blue, green, pink) and labelled.
Fig. 5
Fig. 5
Schematic representation of the MERS-CoV S protein. SP-signal peptide; NTD, N-terminal domain; RBD, receptor binding domain; RBM, receptor binding motif; HR, heptad repeat; TM, transmembrane domain; S1/S2, S Spike protein subunits separated after protease cleavage. Numbering from Lu et al. (2013) and Du et al. (2013a).
Fig. 6
Fig. 6
A schematic depicting the location of primers (blue arrows indicate direction) and oligoprobes (green rectangles) for the earliest RT-rtPCR screening assays and conventional, semi-nested (three primers) RT-PCR confirmatory sequencing assays (Corman et al., 2012a, Corman et al., 2012b). Publication order is noted by first [27th September 2012; red] and second [6th December 2012; orange] coloured rectangles, both by Corman et al. Those assays recommended by the WHO (World Health Organization, 2013b) are highlighted underneath by yellow dots.
Fig. 7
Fig. 7
A speculative model of how humans, camels and other animals may interact to acquire and spread MERS-CoV. Highlighted in red are MERS-CoV virus/RNA and/or antibody-positive hosts.
Fig. 8
Fig. 8
Risks for acquiring MERS-CoV from a DC. This speculative illustration divides risks into those with a droplet component or those with a direct contact component (within the orange circle) and those with a route of ingestion involved (within the blue circle). No route of MERS-CoV acquisition has been proven to date. The dashed boundary between the two implies that both forms of acquisition may co-occur.
Fig. 9
Fig. 9
MERS-CoV detections, age and sex. (A) Plot of the average age (orange circles) of laboratory cases detected in that week and a six day moving average (dashed line). (B) An age and sex pyramid for all MERS-CoV detections worldwide and (C) for those with fatal outcomes from infection. (D) The distribution of age and sex up to but not including the first identifiable case that began the Jeddah-2014 outbreak and (E) those with a fatal outcome. (F) The distribution of age and sex during the Jeddah-2014 outbreak, arbitrarily defined as spanning from the week beginning 17th March 2014 and ending in the week beginning7th July 2014; data are based on laboratory confirmed cases collated into the author's curated line list as at 19th January 2015. Note the changed x-axis scale between B/C and D/E/F/G. Sources of these public data include the World Health Organization, Ministries of Health and FluTrackers (Ministry of Health, Saudi Arabia. 2014). Earlier and subsequent versions of this chart are maintained on a personal website (Mackay, 1997) and blog (Mackay, 2013).
Fig. 10
Fig. 10
Data on MERS-CoV detections among HCWs and based on laboratory confirmed cases collated into the author's curated line list as at 14th January 2015. Sources of these public data include the World Health Organization, Ministries of Health and FluTrackers. Earlier and subsequent versions of this chart are maintained on a personal website (Mackay, 1997) and blog (Mackay, 2013).
Fig. 11
Fig. 11
The time taken for MERS-CoV detections to reach units of 100. The hospital outbreaks in Al-Ahsa and Jeddah triggered the biggest rises in cases. (A) Includes 963 cases worldwide, and 236 of 348 fatal cases as at 14th of January 2015. (B) Monthly detections of MERS-CoV (blue bars) and those of cases who died (red bars) with some dates of interest marked for 2012 to June 2nd 2014. An approximation of when recently born camels are active is indicated. Spring (green) and summer (orange) in the Arabian Peninsula are also shaded. Note the left-hand y-axis scale for 2014 which is 10-fold greater than for 2012/13/15. Sources of these public data include the World Health Organization, Ministries of Health and FluTrackers (Ministry of Health, Saudi Arabia. 2014). Earlier and subsequent versions of this chart are maintained on a personal website (Mackay, 1997) and blog (Mackay, 2013).
Fig. 12
Fig. 12
A representation of sporadic versus sustained human-to-human transmission of a respiratory virus. MERS-CoV does not spread in a sustained manner.
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