MERS: Difference between revisions

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Expanded diagnosis section and added references
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Expanded signs & symptoms and added references
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|newspaper=Associated Press
|newspaper=Associated Press
|date=26 September 2012
|date=26 September 2012
}}</ref> Symptoms of MERS-CoV infection include [[renal failure]] and severe acute [[pneumonia]], which often result in a fatal outcome. The first patient, [[2012 Middle East respiratory syndrome coronavirus outbreak|in June 2012]], had a "7-day history of [[fever]], [[cough]], [[expectoration]], and shortness of breath."<ref name=zaki8nov2012 /> MERS has an estimated [[incubation period]] of 12 days. MERS may occasionally lead to [[pneumonia]], either direct [[viral pneumonia]] or secondary [[bacterial pneumonia]].
}}</ref> The first patient, [[2012 Middle East respiratory syndrome coronavirus outbreak|in June 2012]], had a "7-day history of [[fever]], [[cough]], [[expectoration]], and shortness of breath."<ref name=zaki8nov2012 /> One review of 47 laboratory confirmed cases in Saudi Arabia gave the most common presenting symptoms as fever in 98%, cough in 83%, shortness of breath in 72% and [[myalgia]] in 32% of patients. There were also frequent gastrointestinal symptoms with diarrhea in 26%, vomiting in 21%, abdominal pain in 17% of patients. 72% of patients required [[mechanical ventilation]]. There were also 3.3 males for every female.<ref name=":4" /> One study of a hospital based outbreak of MERS had an estimated [[incubation period]] of 5.5 days (95% [[confidence interval]] 1.9 to 14.7 days).<ref>{{Cite journal|url = http://www.nejm.org/doi/full/10.1056/NEJMoa1306742|title = Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus|last = Assiri|first = A|date = 8/1/2013|journal = NEJM|accessdate = 5/20/2014|doi = 10.1056/NEJMoa1306742}}</ref> MERS can range from asymptomatic disease to severe [[pneumonia]] leading to the [[acute respiratory distress syndrome]] and [[renal failure]].<ref name=":4" />


==Diagnosis==
==Diagnosis==
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For laboratory testing the WHO recommends obtaining samples from the lower respiratory tract via [[bronchoalveolar lavage]] (BAL), sputum sample or tracheal aspirate as these have the highest viral loads.<ref name=":1">{{Cite web|url = http://www.who.int/csr/disease/coronavirus_infections/MERS_Lab_recos_16_Sept_2013.pdf?ua=1|title = Laboratory Testing for Middle East Respiratory
For laboratory testing the WHO recommends obtaining samples from the lower respiratory tract via [[bronchoalveolar lavage]] (BAL), sputum sample or tracheal aspirate as these have the highest viral loads.<ref name=":1">{{Cite web|url = http://www.who.int/csr/disease/coronavirus_infections/MERS_Lab_recos_16_Sept_2013.pdf?ua=1|title = Laboratory Testing for Middle East Respiratory
Syndrome Coronavirus|date = September 2013|accessdate = May 19, 2014|website = |publisher = World Health Organization|last = |first = }}</ref> There have also been studies utilizing upper respiratory sampling via nasopharyngeal swab.<ref>{{Cite journal|url = http://www.sciencedirect.com/science/article/pii/S1473309913702044|title = Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study|last = |first = |date = September 2013|journal = The Lancet Infectious Diseases|accessdate = |doi = 10.1016/S1473-3099(13)70204-4}}</ref>
Syndrome Coronavirus|date = September 2013|accessdate = May 19, 2014|website = |publisher = World Health Organization|last = |first = }}</ref> There have also been studies utilizing upper respiratory sampling via nasopharyngeal swab.<ref name=":4">{{Cite journal|url = http://www.sciencedirect.com/science/article/pii/S1473309913702044|title = Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study|last = |first = |date = September 2013|journal = The Lancet Infectious Diseases|accessdate = |doi = 10.1016/S1473-3099(13)70204-4}}</ref>


Several highly sensitive, confirmatory real-time [[RT-PCR]] assays exist for rapid identification of MERS-CoV from patient-derived samples. These assays attempt to amplify upE (targets elements upstream of the E gene)<ref name=":2">{{Cite journal|url = http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20285|title = Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction|last = Corman|first = V M|date = 2012|journal = Euro Surveill.|accessdate = |doi = |pmid = 23041020}}</ref>, open reading frame 1B (targets the ORF1b gene)<ref name=":2" /> and open reading frame 1A (targets the ORF1a gene).<ref name=":3">{{Cite journal|url = http://www.eurosurveillance.org.laneproxy.stanford.edu/ViewArticle.aspx?ArticleId=20334|title = Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections|last = Corman|first = V M|date = December 6, 2012|journal = Eurosurveillance|accessdate = |doi = |pmid = 23231891}}</ref> The WHO recommends the upE target for screening assays as it is highly sensitive.<ref name=":1" /> In addition, hemi-nested sequencing amplicons targeting RdRp (present in all [[coronavirus]]es) and nucleocapsid (N) gene<ref>{{Cite journal|url = http://jcm.asm.org/content/52/1/67|title = Real-Time Reverse Transcription-PCR Assay Panel for Middle East Respiratory Syndrome Coronavirus|last = Lu|first = Xiaoyan|date = 01/01/2014|journal = J Clin Microbiol|accessdate = 5/20/2014|doi = 10.1128/JCM.02533-13}}</ref> (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.
Several highly sensitive, confirmatory real-time [[RT-PCR]] assays exist for rapid identification of MERS-CoV from patient-derived samples. These assays attempt to amplify upE (targets elements upstream of the E gene)<ref name=":2">{{Cite journal|url = http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20285|title = Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction|last = Corman|first = V M|date = 2012|journal = Euro Surveill.|accessdate = |doi = |pmid = 23041020}}</ref>, open reading frame 1B (targets the ORF1b gene)<ref name=":2" /> and open reading frame 1A (targets the ORF1a gene).<ref name=":3">{{Cite journal|url = http://www.eurosurveillance.org.laneproxy.stanford.edu/ViewArticle.aspx?ArticleId=20334|title = Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections|last = Corman|first = V M|date = December 6, 2012|journal = Eurosurveillance|accessdate = |doi = |pmid = 23231891}}</ref> The WHO recommends the upE target for screening assays as it is highly sensitive.<ref name=":1" /> In addition, hemi-nested sequencing amplicons targeting RdRp (present in all [[coronavirus]]es) and nucleocapsid (N) gene<ref>{{Cite journal|url = http://jcm.asm.org/content/52/1/67|title = Real-Time Reverse Transcription-PCR Assay Panel for Middle East Respiratory Syndrome Coronavirus|last = Lu|first = Xiaoyan|date = 01/01/2014|journal = J Clin Microbiol|accessdate = 5/20/2014|doi = 10.1128/JCM.02533-13}}</ref> (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.

Revision as of 10:55, 20 May 2014

Middle East respiratory syndrome (MERS) is a newly identified syndrome resulting from infections with an apparently new pathogen, the MERS-coronavirus (MERS-CoV).

Signs and symptoms

Early reports[1] compared the virus to severe acute respiratory syndrome (SARS), and it has been referred to as Saudi Arabia's SARS-like virus.[2] The first patient, in June 2012, had a "7-day history of fever, cough, expectoration, and shortness of breath."[1] One review of 47 laboratory confirmed cases in Saudi Arabia gave the most common presenting symptoms as fever in 98%, cough in 83%, shortness of breath in 72% and myalgia in 32% of patients. There were also frequent gastrointestinal symptoms with diarrhea in 26%, vomiting in 21%, abdominal pain in 17% of patients. 72% of patients required mechanical ventilation. There were also 3.3 males for every female.[3] One study of a hospital based outbreak of MERS had an estimated incubation period of 5.5 days (95% confidence interval 1.9 to 14.7 days).[4] MERS can range from asymptomatic disease to severe pneumonia leading to the acute respiratory distress syndrome and renal failure.[3]

Diagnosis

The World Health Organization (WHO) publishes laboratory guidance, surveillance and investigation, case definition, and other materials on its website. The current interim case definition is that a confirmed case is identified in a person with a positive lab test by "molecular diagnostics including either a positive PCR on at least two specific genomic targets or a single positive target with sequencing on a second."[5] A probable case is[5]

  • A person with a febrile acute respiratory illness with clinical, radiological, or histopathological evidence of pulmonary parenchymal disease (e.g. pneumonia or Acute Respiratory Distress Syndrome)
    AND
    Testing for MERS-CoV is unavailable or negative on a single inadequate specimen
    AND
    The patient has a direct epidemiologic link with a confirmed MERS-CoV case.
  • A person with a febrile acute respiratory illness with clinical, radiological, or histopathological evidence of pulmonary parenchymal disease (e.g. pneumonia or Acute Respiratory Distress Syndrome)
    AND
    An inconclusive MERS-CoV laboratory test (that is, a positive screening test without confirmation)
    AND
    A resident of or traveler to Middle Eastern countries where MERS-CoV virus is believed to be circulating in the 14 days before onset of illness.
  • A person with an acute febrile respiratory illness of any severity
    AND
    An inconclusive MERS-CoV laboratory test (that is, a positive screening test without confirmation)
    AND
    The patient has a direct epidemiologic-link with a confirmed MERS-CoV case.

For laboratory testing the WHO recommends obtaining samples from the lower respiratory tract via bronchoalveolar lavage (BAL), sputum sample or tracheal aspirate as these have the highest viral loads.[6] There have also been studies utilizing upper respiratory sampling via nasopharyngeal swab.[3]

Several highly sensitive, confirmatory real-time RT-PCR assays exist for rapid identification of MERS-CoV from patient-derived samples. These assays attempt to amplify upE (targets elements upstream of the E gene)[7], open reading frame 1B (targets the ORF1b gene)[7] and open reading frame 1A (targets the ORF1a gene).[8] The WHO recommends the upE target for screening assays as it is highly sensitive.[6] In addition, hemi-nested sequencing amplicons targeting RdRp (present in all coronaviruses) and nucleocapsid (N) gene[9] (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.

The WHO recommended testing algorithm is to start with a upE RT-PCR and if positive confirm with ORF 1A assay or RdRp or N gene sequence assay for confirmation. If both a upE and secondary assay are positive it is considered a confirmed case.[6]

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.[8] A more specific protein-microarray based assay has also been developed that did not show any cross-reactivity against population samples and serum known to be positive for other betacoronaviruses.[10] Although MERS-CoV has been shown to antagonize endogenous IFN production, treatment with exogenous types I and IIIIFN (IFN-α and IFN-λ, respectively) have effectively reduced viral replication in vitro.[11]

Research

There are no known treatments. Some therapy is achieved from DPP4 inhibitors.[12] SARS virus treatments could hold the key for treatment of MERS-CoV outbreak.[13][14] interferon-α2b and Ribavirin combination do affect MERS-coV replication.[15]

MERS and camels

A study performed between 2010 and 2013, in which the incidence of MERS was evaluated in 310 Dromedary Camels, revealed high titers of neutralizing antibodies to MERS-CoV in the blood serum of these animals, providing an option for passive immunotherapy of patients with MERS.[16] Nevertheless, this option must be thoroughly explored before being considered as reliable. In 2013 a man admitted to the King Abdulaziz University Hospital in Jeddah, who had been looking after a group of sick camels, was diagnosed with the disease;[17] advice to avoid contact with camels or wear breathing masks when around them has been given by the Saudi Ministry of Agriculture.[18] In response "some people have refused to listen to the government's advice"[19] and kiss their camels in defiance of the their government's advice.

Prevention

It is believed that the existing SARS research may provide a useful template for developing vaccines and therapeutics against a MERS-CoV infection.[20][21] Vaccine candidates based on the spike protein have been created by Novavax and Greffex, Inc, and are currently awaiting clinical trials.[22][23] For now, annual influenza vaccinations and 5-year pneumococcal vaccinations are given to reduce or weaken the severity of MERS infection.

History

Collaborative efforts were used in the identification of the MERS-CoV.[24] Egyptian virologist Dr. Ali Mohamed Zaki isolated and identified a previously unknown coronavirus from the lungs of a 60-year-old Saudi Arabian man with pneumonia and acute renal failure.[1] After routine diagnostics failed to identify the causative agent, Zaki contacted Ron Fouchier, a leading virologist at the Erasmus Medical Center (EMC) in Rotterdam, the Netherlands, for advice.[25] Fouchier sequenced the virus from a sample sent by Zaki.

Fouchier used a broad-spectrum "pan-coronavirus" Real-time polymerase chain reaction (RT-PCR) method 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.[24]

On 15 September 2012, Dr. Zaki's findings were posted on ProMED-mail, the Program for Monitoring Emerging Diseases, a public health on-line forum.[26]

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.[24][27] 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[28] based on the virus's RNA obtained from the Qatari case.[2][29]

On 25 September 2012, the WHO announced that it was "engaged in further characterizing the novel coronavirus" and that it had "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."[30] The Erasmus Medical Center in Rotterdam "tested, sequenced and identified" a sample provided to EMC virologist Ron Fouchier by Ali Mohamed Zaki in November 2012.[31]

On 8 November 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).[1]

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), which was adopted by WHO to "provide uniformity and facilitate communication about the disease."[32] Prior to the designation, WHO had used the non-specific designation 'Novel coronavirus 2012' or simply 'the novel coronavirus'.[33]

In April 2014 MERS emerged in the Philippines with a suspected case of a home bound OFW (Overseas Foreign Worker). Several suspected cases involving individuals who were on the same flight as the initial suspected case are being tracked but are believe to have dispersed throughout the country. Another suspected MERS-involved death in Sultan Kudarat province caused the DOH to put out an alert.[34][35][36][37]

MERS was also implicated in an outbreak in April 2014 in Saudi Arabia, where MERS has infected 339 people and 103 MERS-related deaths have been reported since 2012. In response to newly-reported cases and deaths, and the resignation of four doctors at Jeddah’s King Fahd Hospital who refused to treat MERS patients for fear of infection, the government has removed the Minister of Health and set up three MERS treatment centers.[38][39] 18 more cases were reported in early May.[40]

On 2 May 2014, the United States Centers for Disease Control confirmed the first diagnosis of MERS in the United States in Indiana. The man diagnosed was a health care worker who had been in Saudi Arabia a week earlier, and was reported to be in good condition.[41][42] A second patient who also traveled from Saudi Arabia was reported in Orlando, Florida on 12 May 2014.[43][44] On 14 May 2014, officials in the Netherlands reported the first case has appeared.[45] On Saturday, May 17, 2014, a man from Illinois who was a business associate of the first U.S. case (he had met and shook hands with the Indiana health care worker) tested positive for the MERS coronavirus, but has not, as of yet, displayed symptoms (others are probably also, at least temporarily if not permanently, non-symptomatic carriers). The CDC's Dr. David Swerdlow, who is leading the agency's response, said the man, who feels well and has not yet sought and does not yet need medical care, has not been deemed an official case yet and prevention guidelines have not changed. Laboratory tests showed evidence of past infection in his blood.[46]

References

  1. ^ a b c d Ali Mohamed Zaki; Sander van Boheemen; Theo M. Bestebroer; Albert D.M.E. Osterhaus; Ron A.M. Fouchier (8 November 2012). "Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia" (PDF). New England Journal of Medicine. 367 (19): 1814. doi:10.1056/NEJMoa1211721. Cite error: The named reference "zaki8nov2012" was defined multiple times with different content (see the help page).
  2. ^ a b Doucleef, Michaeleen (26 September 2012). "Scientists Go Deep On Genes Of SARS-Like Virus". Associated Press. Retrieved 27 September 2012.
  3. ^ a b c "Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study". The Lancet Infectious Diseases. September 2013. doi:10.1016/S1473-3099(13)70204-4.
  4. ^ Assiri, A (8/1/2013). "Hospital Outbreak of Middle East Respiratory Syndrome Coronavirus". NEJM. doi:10.1056/NEJMoa1306742. Retrieved 5/20/2014. {{cite journal}}: Check date values in: |accessdate= and |date= (help)
  5. ^ a b "Revised interim case definition for reporting to WHO – Middle East respiratory syndrome coronavirus (MERS-CoV)". World Health Organization. 3 July 2013. Retrieved 19 May 2014.
  6. ^ a b c "Laboratory Testing for Middle East Respiratory Syndrome Coronavirus" (PDF). World Health Organization. September 2013. Retrieved May 19, 2014. {{cite web}}: line feed character in |title= at position 47 (help)
  7. ^ a b Corman, V M (2012). "Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction". Euro Surveill. PMID 23041020.
  8. ^ a b Corman, V M (December 6, 2012). "Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections". Eurosurveillance. PMID 23231891.
  9. ^ Lu, Xiaoyan (01/01/2014). "Real-Time Reverse Transcription-PCR Assay Panel for Middle East Respiratory Syndrome Coronavirus". J Clin Microbiol. doi:10.1128/JCM.02533-13. Retrieved 5/20/2014. {{cite journal}}: Check date values in: |accessdate= and |date= (help)
  10. ^ Reusken, C (2013). "Specific serology for emerging human coronaviruses by protein microarray". Eurosurveillance. PMID 23594517. Retrieved 5/20/2014. {{cite journal}}: Check date values in: |accessdate= (help)
  11. ^ "Novel coronavirus well-adapted to humans, susceptible to immunotherapy". eurekalert.org. 2013-02-19. Retrieved 2013-02-19.
  12. ^ Tripp, Ralph (Aug 27, 2013). "Therapeutic Considerations for Middle East Respiratory Syndrome Coronavirus" (PDF). Journal of Antivirals & Antiretrovirals. 5. doi:10.4172/jaa.1000e109. ISSN 1948-5964. {{cite journal}}: Unknown parameter |doi_brokendate= ignored (|doi-broken-date= suggested) (help)CS1 maint: unflagged free DOI (link)
  13. ^ "SARS Virus Treatments Could Hold the Key for Treatment of MERS-CoV Outbreak". Science Daily. Retrieved 19 November 2013.
  14. ^ Momattin, Hisham (October 2013). "Therapeutic Options for Middle East Respiratory Syndrome Coronavirus (MERS-CoV) – possible lessons from a systematic review of SARS-CoV therapy". International Journal of Infectious Diseases. 17 (10): e792–e798. doi:10.1016/j.ijid.2013.07.002. PMID 23993766. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  15. ^ Coleman, Christopher M. (5 September 2013). "Emergence of the Middle East Respiratory Syndrome Coronavirus". PLoS Pathogens. 9 (9): e1003595. doi:10.1371/journal.ppat.1003595. PMC 3764217. PMID 24039577. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: unflagged free DOI (link)
  16. ^ Hemida, MG (2013). "Middle East Respiratory Syndrome (MERS) coronavirus seroprevalence in domestic livestock in Saudi Arabia". Euro Surveillance. 18 (50).
  17. ^ Human Infection with MERS Coronavirus after Exposure to Infected Camels, Saudi Arabia, 2013
  18. ^ Mers virus: Saudis warned to wear masks near camels
  19. ^ Saudi Arabia: Farmers flout Mers warning by kissing camels
  20. ^ "Development of SARS Vaccines and Therapeutics Is Still Needed". medscape.com. 2013. Retrieved 2013-05-29.
  21. ^ Butler D. SARS veterans tackle coronavirus" Nature490(7418),20 (2012).
  22. ^ Parrish, R. (7 June 2013). "Novavax creates MERS-CoV vaccine candidate". Vaccine News. Retrieved 24 June 2013.
  23. ^ Price, J. R. (26 June 2013). "Greffex Does It Again". Business Wire. Retrieved 27 June 2013.
  24. ^ a b c Lu, Guangwen; Liu, Di (2012). "SARS-like virus in the Middle East: A truly bat-related coronavirus causing human diseases" (PDF). Protein & Cell. 3 (11): 803. doi:10.1007/s13238-012-2811-1.
  25. ^ Butler, Declan (15 Jan 2013). "Tensions linger over discovery of coronavirus". Retrieved 22 Apr 2014.
  26. ^ Saey, Tina Hesman (27 February 2013). "Scientists race to understand deadly new virus: SARS-like infection causes severe illness, but may not spread quickly". Science News. Vol. 183, no. 6. p. 5.
  27. ^ Acute respiratory illness associated with a new virus identified in the UK (Report). Health Protection Agency (HPA). 23 September 2012.
  28. ^ Roos, Robert (25 September 2013). UK agency picks name for new coronavirus isolate (Report). University of Minnesota, Minneapolis, MN: Center for Infectious Disease Research & Policy (CIDRAP).
  29. ^ "How threatening is the new coronavirus?". BBC. 24 September 2012. Retrieved 27 September 2012.
  30. ^ "Novel coronavirus infection". World Health Organization. 25 September 2012. Retrieved 27 September 2012.
  31. ^ Heilprin, John (23 May 2013). "WHO: Probe into deadly coronavirus delayed by sample dispute". Geneva: CTV News (Canada). The Associated Press (AP).
  32. ^ "Novel coronavirus update—new virus to be called MERS-CoV". World Health Organization. 16 May 2013.
  33. ^ Global Alert and Response (GAR): Novel coronavirus infection - update (Report). WHO. 23 November 2012.
  34. ^ Michaela del Callar (24 Apr 2014). "3 of 5 quarantined Pinoys in UAE tested negative for MERS-CoV- Pinoy Abroad- GMA News Online". GMA Network Inc. Retrieved 4 May 2014.
  35. ^ Amanda Fernandez (24 Apr 2014). "DOH: Only 6 Etihad EY 0424 passengers left who cannot be contacted- News- GMA News Online". GMA Network Inc. Retrieved 4 May 2014.
  36. ^ Mindanews (22 April 2014). "OFWs from UAE quarantined in GenSan, Sarangani for possible MERS infection- MindaNews". MindaNews. Retrieved 4 May 2014.
  37. ^ Pia Lee-Brago (18 Sep 2013). "First Pinay dies from MERS virus- Headlines, News, The Philippine Star- philstar.com". Philstar. Retrieved 4 May 2014.
  38. ^ Agence France Presse (27 Apr 2014). "Saudi reports 2 more deaths from Mers virus, taking toll to 94- Khaleej Times". Khaleej Times. Retrieved 4 May 2014.
  39. ^ Angus McDowall (27 Apr 2014). "Saudi Arabia has 26 more cases of MERS virus, 10 dead- Reuters". Thomson Reuters. Retrieved 4 May 2014.
  40. ^ http://www.huffingtonpost.com/2014/05/08/saudi-arabia-mers-spreads_n_5285727.html
  41. ^ Mike Stobbe (2 May 2014). "CDC Confirms First Case of MERS in US". ABC News Internet Ventures. Retrieved 4 May 2014.
  42. ^ McKay, Betsy (3–4 May 2014). "American Returns from Mideast With MERS Virus". The Wall Street Journal. pp. A3. {{cite news}}: |access-date= requires |url= (help)
  43. ^ Angus McDowall (12 May 2014). "CDC announces second imported case of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in the United States". Retrieved 12 May 2014.
  44. ^ Kate Santich (12 May 2014). "1st MERS case reported in Central Florida". ABC News Internet Ventures. Retrieved 12 May 2014.
  45. ^ "1st MERS case reported in the Netherlands". Chicago Tribune. 14 May 2014. Retrieved 14 May 2014.
  46. ^ http://www.nbcnews.com/storyline/mers-mystery/illinois-man-third-u-s-mers-infection-cdc-says-n108066