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MERS-related coronavirus

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MERS-related coronavirus
Virus classification
Group:
Group IV ((+)ssRNA)
Order:
Nidovirales
Family:
Coronaviridae
Subfamily:
Coronavirinae
Genus:
Betacoronavirus
MERS-related coronavirus
DateJune 12, 2012 (2012-06-12)–present
Location Saudi Arabia
 Qatar
 Tunisia
 Jordan
 France
 England
 Germany
Casualties
44 cases
23 deaths[1]

The Middle East Respiratory Syndrome Coronavirus (MERS-CoV)[2] (Arabic:متلازمة جهاز التنفس الشرق أوسطية ( فيروس كورونا) ) is a novel coronavirus (CoV) first reported on 24 September 2012 on Promed [3] by an Egyptian virologist, Dr Ali Mohamed Zaki in Jeddah, Saudi Arabia. Dr Zaki isolated and identified a previously unknown coronavirus from the lungs of a 60 year old male patient with acute pneumonia and fatal renal failure.[4][5][6] He posted his findings on ProMed-mail.[3][5] MERS-CoV is a sixth new type of coronavirus being like SARS (but still distinct from it and from the common-cold coronavirus). Until 23 May 2013 MERS-CoV has frequently been been referred to as a SARS-like virus[7] or simply the novel coronavirus and colloquially on messageboards as 'Saudi SARS' (e.g. Guardian and Yahoo in the UK and CNN in the US and Toronto and Ottawa media in Canada). Most infections with human coronaviruses are mild and associated with common colds. Some animal and human coronaviruses, like MERS-CoV, may cause severe and sometimes fatal infections in humans. MERS-CoV does not have many of the grave characteristics of SARS-CoV (severe acute respiratory syndrome) which caused fatal epidemics in Hong Kong and Canada in 2002/2003.[4] [8] Fortunately global surveillance of potential epidemics and preparation has improved since and because of the SARS epidemic.[9][notes 1] In November 2012 Dr Zaki sent a virus sample to confirm his findings to EMC virologist Ron Fouchier, a leading coronavirus researcher at the Erasmus Medical Center in Rotterdam.[10] The second laboratory-proven case was in London confirmed by the UK Health Protection Agency (HPA).[11][12] The HPA named the virus the London1_novel CoV 2012.[13] In November 8, 2012 in an article published in the New England Journal of Medicine, Dr Zaki and co-authors from the Erasmus Medical Center, published more details, including a scientific name, Human Coronavirus-Erasmus Medical Center (HCoV-EMC) which was then used in scientific literature.[4] In the article they noted four respiratory human coronaviruses (HCoV) known to be endemic: 229E, OC43, NL63, and HKU1.[4] In May 2013 the Coronavirus Study Group of the International Committee on Taxonomy of Viruses adopted the official designation, the Middle East Respiratory Syndrome Coronavirus (MERS-CoV),[2] which was adopted by the World Health Organization to "provide uniformity and facilitate communication about the disease" [14] to replace the unscientific designations Novel coronavirus 2012 or simply 'novel coronavirus' which were consistently used by WHO since 2012.[15]

Ten of the 22 people who died and 22 of 44 cases reported were in Saudi Arabia and over 80% were male.[16] By May 2013 eight countries were affected by MERS-CoV: Jordan, Saudi Arabia, Qatar, the United Kingdom, France, Germany, the United Arab Emirates and Tunisia.[17]

Designation and Identification

Collaborative efforts were utilized in the identification of MERS-CoV.[11] Dr Zaki isolated and identified a previously unknown coronavirus from the lungs of a 60-year-old Saudi Arabian man with acute pneumonia and fatal renal failure.[4][5] He used a broad-spectrum "pan-coronavirus" RT-PCR method and got a positive result. On September 15, 2012 Dr Zaki's findings were posted on ProMed-mail,[3] the Program for Monitoring Emerging Diseases, a public health on-line forum [5][7] The UK Health Protection Agency (HPA) confirmed the diagnosis of severe respiratory illness associated with a new type of coronavirus in a second patient, a 49-year-old Qatari man who had recently been flown into the UK. He died from an acute, serious respiratory illness in a London hospital.[11][12] In September 2012, the United Kingdom's Health Protection Agency (HPA) named it the London1_novel CoV 2012 and produced the virus' preliminary phylogenetic tree, the genetic sequence of the virus [13] based on the virus's RNA obtained from the Qatari case.[18][19] On September 25, 2012 the World Health Organization (WHO) announced that it is "engaged in further characterizing the novel coronavirus" and that it has "immediately alerted all its Member States about the virus and has been leading the coordination and providing guidance to health authorities and technical health agencies."[20] The Erasmus Medical Center in Rotterdam "tested, sequenced and identified" a sample provided to EMC virologist Ron Fouchier, a leading coronavirus researcher, by Ali Mohamed Zaki in November 2012.[10] In September 2012 Ron Fouchier speculated that the virus might have originated in bats.[21] In November 8, 2012 in an article published in the New England Journal of Medicine, Dr Zaki and co-authors from the Erasmus Medical Center, published more details, including a tentative name, Human Coronavirus-Erasmus Medical Center (HCoV-EMC), the virus’s genetic makeup and closest relatives, including SARs.[4] In May 2013 the Coronavirus Study Group of the International Committee on Taxonomy of Viruses adopted the official designation, the Middle East Respiratory Syndrome Coronavirus (MERS-CoV),[2] which was adopted by the World Health Organization to "provide uniformity and facilitate communication about the disease." [22] Prior to the designation WHO had used the non-specific designation 'Novel coronavirus 2012' or simply 'the novel coronavirus'[15]

Fouchier and his team of researchers successfully sequenced the whole genome of the new coronavirus naming the viral strain Human Coronavirus-Erasmus Medical Center (hCoV-EMC) after their research center. They published its genomic sequence in the GenBank (accession code: JX869059) in the fall of 2012.[11]

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 [23] of the Middle East respiratory syndrome coronavirus.[23] Fouchier's creation of a dangerous and highly contagious strain of the H5N1 virus resulted in a global controversy [24] ignited by fears that his academic articles published in journals might provide "a cookbook for a biological attack".[23] America temporarily suspended funding of research projects on dangerous viruses. 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."[23] Dr Zaki was fired from his job as a result of sharing his findings.[25][26][27][28]

Quantitative polymerase chain reaction (qPCR) was used to test for distinguishing features of a number of known coronaviruses (such as OC43, 229R, NL63, and SARS-CoV), as well as for RNA-dependent RNA polymerase (RdRp), a gene conserved in all coronaviruses known to infect humans. While the screens for known coronaviruses were all negative, the RdRp screen was positive.[11]

History

On 21 February 2013, WHO stated that there had been 13 laboratory-confirmed cases, 6 cases (4 fatal) from Saudi Arabia, 2 cases (both fatal) from Jordan, 2 cases from Qatar, and 3 from the UK.[29]

Outbreaks in Saudi Arabia

The first known case of a previously unknown coronavirus, was identified in a 60-year-old Saudi Arabian man with acute pneumonia who died of renal failure in June 2012.[4][18][30] As of 12 May 2013 two more deaths have been reported in the al-Ahsa region of Saudi Arabia. In the latest cluster of infections, 15 cases had been confirmed, and nine of those patients had died.[31] Ten of the 22 people who died and 22 of 44 cases reported were in Saudi Arabia.[16] An unconfirmed case in another Saudi citizen, for which no clinical information was available, was also reported around this time. On 22 September 2012, the Saudi Ministry of Health (MOH) announced that the two cases involving Saudi citizens, caused by what they termed a “rare pattern of coronavirus,” had both proven fatal.

Two of the Saudi Arabia cases were from the same family and from that family at least one additional person presented similar symptoms but tested negative for the novel coronavirus.[32]

In March 2013, the Saudi Arabia Ministry of Health reported the death of a 39-year-old man, the 15th case and 9th death reported to WHO.[33] On 2 May 2013, the Saudi Arabia Ministry of Health announced five people died and two other people were in critical condition with confirmed cases of a SARS-like virus.[34] The delays in obtaining data and absence of basic information (which would usefully include: sex, age, other medical conditions and smoking status) have been noted and decried by Dr Margaret Chan and in Pro-Med comments on numerous briefings. At the annual meeting of the world’s health ministers Chan, director-general of the World Health Organization, said the virus was now her “greatest concern.”[35]

United Kingdom

The second patient was a 49 year old Qatari man who had visited Saudi Arabia before falling ill and being flown privately by air ambulance from Doha to London on 11 September where he was admitted to St Mary's Hospital (later being transferred to St Thomas's Hospital (http://www.promedmail.org/direct.php?id=20120923.1305982). As a result of Dr Zaki's post on Pro-MED the novel coronavirus was quickly identified.[36][37] He was treated for respiratory disease and, like the first patient in Saudi Arabia, died of renal failure in October 2012. In early October 2012, the Qatari patient residing in the United Kingdom died as well.[5][36][37][38][39] This virus is referred to as Saudi SARS in informal settings (see message boards) to differentiate it from the Hong Kong SARS.

In February 2013, the first UK case of the novel coronavirus was confirmed in Manchester in an elderly man who had recently visited the Middle East and Pakistan; it was the 10th case globally.[40] The man's son whom he visited in hospital in Birmingham was immuno-suppressed because of a brain tumour contracted the virus, providing the first clear evidence for person-to-person transmission.[41][42] He died on 19 February 2013.[43][44]

France

On 7 May 2013 one case was confirmed in Nord departement of France, the man had previously travelled to Dubai, United Arab Emirates.[45] On May 12, a case of contamination from human to human, a man previously hospitalized in the same room as the first patient, was confirmed by French Ministry of Social Affairs and Health.[46]

France reported its first death from the MERS near the end of May.[47]

Tunisia

On 20 May 2013 the novel coronavirus reached Tunisia killing one man and infecting two of his relatives. Tunisia is the eighth country to be affected by MERS-CoV, along with Jordan, Saudi Arabia, Qatar, the United Kingdom, France, Germany, and the United Arab Emirates.[48]

Symptoms

Early reports [4] compared the virus to severe acute respiratory syndrome (SARS) and it has been referred to as Saudi Arabia's SARS-like virus.[18] Close contact spreads the virus.[49]

Symptoms of MERS-CoV infection include renal failure and severe acute pneumonia, which often result in a fatal outcome. The first patient had a "7-day history of fever, cough, expectoration, and shortness of breath." [4] In humans, the virus has a strong tropism for nonciliated bronchial epithelial cells, and has been shown to effectively evade innate immune responses and antagonize interferon (IFN) production in these cells. This tropism is unique in that most respiratory viruses target ciliated cells.[50][51]

Real time tests

Several highly sensitive, confirmatory real-time RT-PCR assays exist for rapid identification of MERS-CoV from patient-derived samples (such as bronchoalveolar lavage or sputum): upE (targets elements upstream of the E gene) and 1A (targets the ORF1a gene). In addition, hemi-nested sequencing amplicons targeting RdRp (present in all coronaviruses) and N gene (specific to MERS-CoV) fragments can be generated for confirmation via sequencing. Reports of potential polymorphisms in the N gene between isolates highlight the necessity for sequence-based characterization. Protocols for biologically safe immunofluorescence assays (IFA) have also been developed; however, antibodies against betacoronaviruses are known to cross-react within the genus. This effectively limits their use to confirmatory applications.[52] Although hCoV-EMC has been shown to antagonize endogenous IFN production, treatment with exogenous types I and III IFN (IFN-α and IFN-λ, respectively) have effectively reduced viral replication in vitro.[50][53]

Surveillance

On 13 February 2013, WHO stated "the risk of sustained person-to-person transmission appears to be very low."[42]

The European Centre for Disease Prevention and Control (ECDC), an independent agency of the European Union (EU) [54] established in 2005 to strengthen Europe's defence against infectious diseases, is monitoring MERS-CoV.[55]

Origin

In September 2012 Ron Fouchier speculated that the virus might be an animal origin originating in bats.[33][56] Sequencing and subsequent analysis indicated that the novel coronavirus shared high sequence homology with both bat[11] and porcine coronaviruses, the highest of which were bat coronaviruses HKU4 and HKU5 (about 94% similarity; carried by the genus Pipistrellus).[39][57] An article published in the Emerging Infectious Disease Journal in March 2013 identified bat coronaviruses carried by the genus Pipistrellus that differed from hCoV-EMC by as little as 1.8%. There are several species of Pipistrellus in the Arabian Peninsula. The high potential for use of cave-derived water and bat guano strongly suggests that they may be the pre-crossover zoonotic reservoir. A zoonosis is an infectious disease that is transmitted between species. In the same study it was shown that hCoV-EMC was capable of infecting bat and porcine cell lines in addition to human cells. This property would indicate a low barrier for transmission between hosts.[57][58][59]

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 (ACE2). However, recent studies have indicated that neutralization of ACE2 by recombinant antibodies does not prevent MERS-CoV infection. Further studies by the same group have identified the exopeptidase, dipeptyl peptidase 4 (DPP4; also known as CD26) 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.[51][59][60][61]

WHO urges sharing of information on new coronavirus

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. Ten of the 22 people who died and 22 of 44 cases reported were in Saudi Arabia.[16]

Taxonomy

The virus MERS-CoV belongs to the genus Betacoronavirus,[39] as does SARS-CoV.[62]

MERS-CoV is more closely related to the bat coronaviruses HKU4 and HKU5 (lineage 2C) than it is to SARS-CoV (lineage 2B) (2, 9). 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 (ICTV).

  • Mnemonic:
  • Taxon identifier:
  • Scientific name: Middle East respiratory syndrome coronavirus [2]
  • Common name: MERS-CoV
  • Synonym: Severe acute respiratory syndrome coronavirus
  • Other names:
      • novel coronavirus (nCoV)
      • London1_novel CoV 2012.[13]
      • Human Coronavirus-Erasmus Medical Center (HCoV-EMC)
  • Rank:
  • Lineage:
  • Virus hosts:

Strains:

    • Isolate:
    • Isolate:
  • NCBI

Notes

  1. ^ As noted in the article published in The Economist on April 20, 2013 ProMED is an online reporting programme at the International Society for Infectious Diseases are part of improved surveillance systems that "use a range of sources to provide quick information on emerging threats" that were not available at the time of SARS outbreak (in 2003), H5N1 bird flu (in 2005) and H1N1 swine flu (in 2009).

References

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