The Middle East respiratory syndrome coronavirus, also termed EMC/2012, is positive-sense, single-stranded
RNA novel species of the genus Betacoronavirus.
First called novel coronavirus 2012 or simply novel coronavirus, it was first reported in
2012 after genome sequencing of a virus isolated from sputum samples from patients who fell
ill in a 2012 outbreak of a new flu.
As of 14 May 2014, MERS-CoV cases have been reported in several countries, including Saudi
Arabia, Malaysia, Jordan, Qatar, Egypt, the United Arab Emirates, Kuwait, Oman, Algeria,
Bangladesh, the Philippines, Indonesia, the United Kingdom, and the United States.
According to an article in the 1 July 2014 International New York Times, there were over
700 documented cases in 20 countries with 250 deaths attributed to the illness.
Almost all those infected were somehow linked to Saudi Arabia.
In the same article it was reported that Saudi authorities' errors in response to MERS-CoV
were a contributing factor to the spread of this deadly virus.
Virology The virus MERS-CoV is a new member of the
beta group of coronavirus, Betacoronavirus, lineage C. MERS-CoV genomes are phylogenetically
classified into two clades, clade A and B.
The earliest cases of MERS were of clade A clusters, and new cases are genetically distinct.
MERS-CoV is distinct from SARS and distinct from the common-cold coronavirus and known
endemic human betacoronaviruses HCoV-OC43 and HCoV-HKU1.
Until 23 May 2013, MERS-CoV had frequently been referred to as a SARS-like virus, or
simply the novel coronavirus, and early it was referred to colloquially on messageboards
as the "Saudi SARS".
Origin The first confirmed case was reported in Saudi
Arabia 2012.
Egyptian virologist Dr. Ali Mohamed Zaki isolated and identified a previously unknown coronavirus
from the man's lungs.
Dr. Zaki then posted his findings on 24 September 2012 on ProMED-mail.
The isolated cells showed cytopathic effects, in the form of rounding and syncytia formation.
A second case was found in September 2012.
A 49-year-old male living in Qatar presented similar flu symptoms, and a sequence of the
virus was nearly identical to that of the first case.
In November 2012, similar cases appeared in Qatar and Saudi Arabia.
Additional cases were noted, with deaths associated, and rapid research and monitoring of this
novel coronavirus began.
It is not certain whether the infections are the result of a single zoonotic event with
subsequent human-to-human transmission, or if the multiple geographic sites of infection
represent multiple zoonotic events from a common unknown source.
A study by Ziad Memish of Riyadh University and colleagues suggests that the virus arose
sometime between July 2007 and June 2012, with perhaps as many as 7 separate zoonotic
transmissions.
Among animal reservoirs, CoV has a large genetic diversity yet the samples from patients suggest
a similar genome, and therefore common source, though the data are limited.
It has been determined through molecular clock analysis, that viruses from the EMC/2012 and
England2012 date to early 2011 suggesting that these cases are descended from a single
zoonotic event.
It would appear the MERS-CoV has been circulating in the human population for greater than one
year without detection and suggests independent transmission from an unknown source.
Tropism In humans, the virus has a strong tropism
for nonciliated bronchial epithelial cells, and it has been shown to effectively evade
the innate immune responses and antagonize interferon production in these cells.
This tropism is unique in that most respiratory viruses target ciliated cells.
Due to the clinical similarity between MERS-CoV and SARS-CoV, it was proposed that they may
use the same cellular receptor; the exopeptidase, angiotensin converting enzyme 2.
However, it was later discovered that neutralization of ACE2 by recombinant antibodies does not
prevent MERS-CoV infection.
Further research identified dipeptyl peptidase 4 as a functional cellular receptor for MERS-CoV.
Unlike other known coronavirus receptors, the enzymatic activity of DPP4 is not required
for infection.
As would be expected, the amino acid sequence of DPP4 is highly conserved across species
and is expressed in the human bronchial epithelium and kidneys.
Bat DPP4 genes appear to have been subject to a high degree of adaptive evolution as
a response to coronavirus infections, so the lineage leading to MERS-CoV may have circulated
in bat populations for a long period of time before being transmitted to people.
Transmission On 13 February 2013, the World Health Organization
stated "the risk of sustained person-to-person transmission appears to be very low."
The cells MERS-CoV infects in the lungs only account for 20% of respiratory epithelial
cells, so a large number of virions are likely needed to be inhaled to cause infection.
As of 29 May 2013, the WHO is now warning that the MERS-CoV virus is a "threat to entire
world."
However, Dr. Anthony S. Fauci of the National Institutes of Health in Bethesda, Maryland,
stated that as of now MERS-CoV "does not spread in a sustained person to person way at all."
Dr. Fauci stated that there is potential danger in that it is possible for the virus to mutate
into a strain that does transmit from person to person.
The infection of healthcare workers has led to concerns of human to human transmission.
The Centers for Disease Control and Prevention list MERS as transmissible from human-to-human.
From their FAQ, in answer to the question "Does MERS-CoV spread from person to person?",
they answer "MERS-CoV has been shown to spread between people who are in close contact.
Transmission from infected patients to healthcare personnel has also been observed.
Clusters of cases in several countries are being investigated."
There is also a New York Times article which provides some correlative context for this.
However on the 28th of May, the CDC revealed that the Illinois man who was originally thought
to have been the first incidence of person to person spread, had in fact tested negative
for MERS-CoV.
After completing additional and more definitive tests using a neutralising antibody assay,
experts at the CDC have concluded that the Indiana patient did not spread the virus to
the Illinois patient.
Tests concluded that the Illinois man had not been previously infected.
It is possible for silent MERS to occur, this is when the patient does not develop symptoms.
Early research has shown that up to 20% of cases show no signs of active infection but
have MERS-CoV antibodies in their blood.
Natural reservoir Early research suggested the virus is related
to one found in the Egyptian tomb bat.
In September 2012 Ron Fouchier speculated that the virus might have originated in bats.
Work by epidemiologist Ian Lipkin of Columbia University in New York showed that the virus
isolated from a bat looked to be a match to the virus found in humans.
2c betacoronaviruses were detected in Nycteris bats in Ghana and Pipistrellus bats in Europe
that are phylogenetically related to the MERS-CoV virus.
Recent work links camels to the virus.
An ahead-of-print dispatch for the journal Emerging Infectious Diseases records research
showing the coronavirus infection in dromedary camel calves and adults, 99.9% matching to
the genomes of human clade B MERS-CoV.
At least one person who has fallen sick with MERS was known to have come into contact with
camels or recently drank camel milk.
On 9 August 2013, a report in the journal The Lancet Infectious Diseases showed that
50 out of 50 blood serum from Omani camels and 15 of 105 from Spanish camels had protein-specific
antibodies against the MERS-CoV spike protein.
Blood serum from European sheep, goats, cattle, and other camelids had no such antibodies.
Countries like Saudi Arabia and the United Arab Emirates produce and consume large amounts
of camel meat.
The possibility exists that African or Australian bats harbor the virus and transmit it to camels.
Imported camels from these regions might have carried the virus to the Middle East.
In 2013 MERS-CoV was identified in three members of a dromedary camel herd held in a Qatar
barn, which was linked to two confirmed human cases who have since recovered.
The presence of MERS-CoV in the camels was confirmed by the National Institute of Public
Health and Environment of the Ministry of Health and the Erasmus Medical Center, the
Netherlands.
None of the camels showed any sign of disease when the samples were collected.
The Qatar Supreme Council of Health advised in November 2013 that people with underlying
health conditions, such as heart disease, diabetes, kidney disease, respiratory disease,
the immunosuppressed, and the elderly, avoid any close animal contacts when visiting farms
and markets, and to practice good hygiene, such as washing hands.
A further study on dromedary camels from Saudi Arabia published in December 2013 revealed
the presence of MERS-CoV in 90% of the evaluated dromedary camels, suggesting that dromedary
camels not only could be the main reservoir of MERS-CoV, but also the animal source of
MERS.
According to the 27 March 2014 MERS-CoV summary update, recent studies support that camels
serve as the primary source of the MERS-CoV infecting humans, while bats may be the ultimate
reservoir of the virus.
Evidence includes the frequency with which the virus has been found in camels to which
human cases have been exposed, seriological data which shows widespread transmission in
camels, and the similarity of the camel CoV to the human CoV.
On 6 June 2014, the Arab News newspaper highlighted the latest research findings in the New England
Journal of Medicine in which a 44-year-old Saudi man who kept a herd of nine camels died
of MERS in November 2013.
His friends said they witnessed him applying a topical medicine to the nose of one of his
ill camels--four of them reportedly sick with nasal discharge--seven days before he himself
became stricken with MERS.
Researchers sequenced the virus found in one of the sick camels and the virus that killed
the man, and found that their genomes were identical.
In that same article, the Arab News reported that as of 6 June 2014, there have been 689
cases of MERS reported within the Kingdom of Saudi Arabia with 283 deaths.
Taxonomy MERS-CoV is more closely related to the bat
coronaviruses HKU4 and HKU5 than it is to SARS-CoV, sharing more than 90% sequence identity
with their closest relationships, bat coronaviruses HKU4 and HKU5 and therefore considered to
belong to the same species by the International Committee on Taxonomy of Viruses.
Mnemonic: Taxon identifier:
Scientific name: Middle East respiratory syndrome coronavirus
Common name: MERS-CoV Synonym: Severe acute respiratory syndrome
coronavirus Other names:
novel coronavirus London1 novel CoV 2012
Human Coronavirus Erasmus Medical Center/2012
Rank: Lineage:
› Viruses › ssRNA viruses
› Group: IV; positive-sense, single-stranded RNA viruses
› Order: Nidovirales › Family: Coronaviridae
› Subfamily: Coronavirinae › Genus: Betacoronavirus› Species: Betacoronavirus
1, Human coronavirus HKU1, Murine coronavirus, Pipistrellus bat coronavirus HKU5, Rousettus
bat coronavirus HKU9, Severe acute respiratory syndrome-related coronavirus, Tylonycteris
bat coronavirus HKU4, MERS-CoV
Virus hosts: Homo sapiens
Bats Swine
Strains: Isolate:
Isolate: NCBI
Microbiology The virus grows readily on Vero cells and
LLC-MK2 cells.
Research and patent Saudi officials had not given permission to
Dr. Zaki to send a sample of the virus to Fouchier and they were angered when Fouchier
claimed the patent on the full genetic sequence of the Middle East respiratory syndrome coronavirus.
The editor of The Economist observed, "Concern over security must not slow urgent work.
Studying a deadly virus is risky.
Not studying it is riskier."
Dr. Zaki was fired from his job at the hospital as a result of sharing his sample and findings.
At their annual meeting of the World Health Assembly in May 2013, WHO chief Margaret Chan
declared that intellectual property, or patents on strains of new virus, should not impede
nations from protecting their citizens by limiting scientific investigations.
Deputy Health Minister Ziad Memish raised concerns that scientists who held the patent
for the MERS-CoV virus would not allow other scientists to use patented material and were
therefore delaying the development of diagnostic tests.
Erasmus MC responded that the patent application did not restrict public health research into
MERS coronavirus, and that the virus and diagnostic tests were shipped—free of charge—to all
that requested such reagents.
Corona Map There are a number of mapping efforts focused
on tracking MERS coronavirus.
On 2 May 2014, the Corona Map was launched to track the MERS coronavirus in realtime
on the world map.
The data is officially reported by WHO or the Ministry of Health of the respective country.
HealthMap also tracks case reports with inclusion of news and social media as data sources as
part of HealthMap MERS.
See also
Outbreak Super-spreader
Virulence Novel virus
HCoV-EMC/2012 London1 novel CoV/2012
Tylonycteris bat coronavirus HKU4 Rousettus bat coronavirus HKU9
European Centre for Disease Prevention and Control
References
External links Emergence of the Middle East Respiratory Syndrome
Coronavirus MERS-CoV Complete Genome
Emerging viruses Molecular Illustration of MERS-Coronavirus
Philippines still MERS-CoV free – DOH