MERS-COV (25): RISK ASSESSMENT, WHO

Posted on 08TH AUG 2018
tagged MERS-CoV, Worldwide

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Date: Wed 8 Aug 2018
Source: WHO MERS Global Summary Summary of Current Situation [edited]
http://www.who.int/csr/disease/coronavirus_infections/risk-assessment-au...

WHO MERS global summary and assessment of risk, August 2018
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Global summary
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Between 2012 and [30 Jun 2018], 2229 laboratory confirmed cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection were reported to WHO, 83 per cent of whom were reported by the Kingdom of Saudi Arabia (figure 1. Epidemic curve of MERS-CoV human cases as of [30 Jun 2018] [see URL above]). In total, cases have been reported from 27 countries in the Middle East, North Africa, Europe, the United States of America, and Asia (table 1. Number of laboratory-confirmed MERS cases reported by countries, by year, since 2012, as of [20 Jun 2018] [see URL above]). Males above the age of 60 with an underlying medical condition, such as diabetes, hypertension and renal failure, are at a higher risk of severe disease, including death. To date, 791 individuals have died (crude case fatality rate [CFR] 35.5 per cent).

Since the last global update published on [21 Jul 2017], 189 laboratory-confirmed cases of MERS-CoV from 4 countries were reported to WHO (182 from Saudi Arabia, 3 from Oman, 3 from the United Arab Emirates, and 1 from Malaysia), of whom 60 (31.7 per cent) have died. Among these cases, 75.5 per cent were male and the median age was 54 years old (interquartile range [IQR] 40-65.5; range 10-93 years). The median age is similar to the median age of all cases reported to WHO since 2012 (52 years old, IQR 37-65).

At the time of writing, 19 of 189 patients (10 per cent) were reported as asymptomatic or having mild [clinical disease]. At least 1 underlying condition was reported in 137 cases (72 per cent) since the last update, including chronic renal failure, heart disease, diabetes mellitus, and hypertension.

Overall, the epidemiology, transmission patterns, clinical presentation of MERS patients and viral characteristics reported since the last update are consistent with past patterns described in previous WHO risk assessments: MERS-CoV is a zoonotic virus that has repeatedly entered the human population via direct or indirect contact with infected dromedary camels in the Arabian Peninsula. Limited, non-sustained human-to-human transmission mainly in health care settings continues to occur, primarily in Saudi Arabia. The risk of exported cases to areas outside of the Middle East due to travel remains significant.

While there have been significant improvements in surveillance for MERS, especially in the Middle East, and in reacting to suspect clusters, early identification in the community and in health care systems, compliance with the infection prevention and control measures and contact follow up remain major challenges for MERS outbreak prevention and control.

The continued importance of MERS-CoV in healthcare settings
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Since the last global update of [21 Jul 2017], 17 of the 45 secondary cases reported to WHO were associated with transmission in a health care facility. These cases included health care workers (12 cases), patients sharing rooms/wards with MERS patients, or family visitors.

Though not unexpected, these transmission events continue to be deeply concerning, given that MERS-CoV is still a relatively rare disease about which medical personnel in health care facilities have low awareness. Globally, awareness for MERS is low and, because symptoms of MERS-CoV infection are non-specific, initial cases are sometimes easily missed. With improved compliance in infection prevention and control, namely adherence to the standard precautions at all times, human-to-human transmission in health care facilities can be reduced and possibly eliminated with additional use of transmission based precautions.

Since the last update of July 2017, several MERS clusters were reported, including the following:

- In July-August 2017, 2 clusters of MERS were reported from AL-Jawf Region, Saudi Arabia. These clusters were not epidemiologically linked.

The 1st health care associated cluster included 13 cases, 2 who died. Among the 12 secondary cases, 10 were asymptomatic, including 8 health care workers.

The 2nd cluster included 7 cases, 6 of whom were household contacts. Of the 6 secondary cases, 5 were asymptomatic. None of the cases identified in this cluster were health care workers and there were no fatalities.

- In January-February 2018, a health care associated cluster was reported in Hafr Al Batin Region, Saudi Arabia. The cluster included 4 cases and 1 death, including 3 asymptomatic health care workers identified through contact tracing.

- In February-March 2018, a health care associated cluster of 6 cases occurred in a hospital in Riyadh, Saudi Arabia. Of the 6 cases, none were health care workers and 3 were fatal.

- In March 2018, there was a household cluster reported from Jeddah, Saudi Arabia. This cluster included 3 individuals, all of whom survived.

- In May-June 2018, a household cluster was reported from the Najran Region, Saudi Arabia. The index case reported regular contact with dromedary camels. A total of 10 family contacts and one health care worker were identified as 2ary cases. Out of the 12 cases identified in this cluster, none were fatal.

Since 2015, the increase in the number of asymptomatic contacts identified in health care settings is due to a policy change by the Ministry of Health of the Kingdom of Saudi Arabia, in which all high-risk contacts are tested for MERSCoV regardless of the development of symptoms. This comprehensive contact identification, follow-up, testing and isolation of positive cases continues into 2018.

Drivers of transmission and the exact modes of transmission in health care settings still are unclear and are currently the focus of collaborative scientific research. From observational studies, transmission in health care settings is believed to have occurred before adequate infection prevention and control procedures were applied and cases were isolated. Investigations at the time of the outbreaks indicate that aerosolizing procedures conducted in crowded emergency departments or medical wards with sub-optimal infection prevention and control measures in place resulted in human-to-human transmission and environmental contamination.

Community-acquired cases and reported links to dromedary camels
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Since the last update, 56 human cases are believed to have been infected in the community. Of these 56 reported cases, 37 (66.1 per cent) reported direct or indirect contact with dromedaries in Saudi Arabia (33 cases), Oman (2 cases), the United Arab Emirates (one case) and Malaysia (one case; contact with dromedary was in Saudi Arabia).

Improvement in multi-sectoral investigation of community acquired cases is evident, including testing of dromedary animals/herds in the vicinity of community-acquired laboratory-confirmed cases and follow-up of human contacts of laboratory-confirmed cases. The ministries of health in affected countries notify the ministries of agriculture when human cases report a link with animals. Investigations in animals are carried out by officials from the ministries of agriculture and results, if positive for MERS-CoV, are reported to OIE.

Exported cases identified outside the Middle East Since the last update, 1 case was reported outside of the Middle East. The case, a 55 year old, had recently returned from Jeddah to Malaysia in December 2017. The patient was treated and recovered, contacts were identified and followed and no further cases were identified by authorities in Malaysia.

Summary - information available from 2012 to date [as of 30 Jun 2018]
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Thus far, no sustained human-to-human transmission has occurred anywhere in the world, however limited non-sustained human-to-human transmission in health care facilities remains a prominent feature of this virus. WHO continues to work with health authorities in the affected countries to prevent and minimize health care-associated cases. WHO understands that health authorities in affected countries, especially those in the most affected countries, are aggressively investigating cases and contacts, including testing for MERS-CoV among asymptomatic contacts, and applying mitigation measures to stop human-to-human transmission in health care settings. These efforts are proving successful in mitigating the size of outbreaks.

Of all laboratory-confirmed cases reported to date (n=2228), the median age is 52 (IQR 37-65) and 67.2 per cent are male.

At the time of reporting, 21 per cent of the 2228 cases were reported to have no or mild symptoms, while 46 per cent had severe disease or died. Overall, 18.6 per cent of the cases reported to date are health care workers.

Since 2012, 27 countries have reported cases of MERS-CoV infection. In the Middle East: Bahrain, Egypt, Iran, Jordan, Kuwait, Lebanon, Oman, Qatar, Saudi Arabia, the United Arab Emirates and Yemen; in Africa: Algeria and Tunisia; in Europe: Austria, France, Germany, Greece, Italy, the Netherlands, Turkey and the United Kingdom; in Asia: China, the Republic of Korea, Malaysia, the Philippines and Thailand; and in the Americas: the United States of America (Table 1 [available at source URL]).

The majority of cases (about 83 per cent) have been reported from Saudi Arabia (figure 1 [see source URL]).

Populations in close contact with dromedaries (such as farmers, abattoir workers, shepherds, dromedary owners) and health care workers caring for MERS-CoV patients are believed to be at higher risk of infection. Healthy adults infected with MERS-CoV tend to have mild subclinical or asymptomatic infections. To date, limited human-to-human transmission has occurred between close contacts of confirmed cases in household settings.

More efficient human-to-human transmission occurs in health care settings due to inadequate and/or incomplete compliance with the infection prevention and control measures and delay in triage or isolation of suspected MERS patients.

Health care-associated transmission has been documented in several countries between 2012-2016, including Saudi Arabia, Jordan, the United Arab Emirates, France, the United Kingdom, and the Republic of Korea with varying outbreak sizes (2-180 reported cases per outbreak).

The largest outbreak outside of the Middle East occurred in the Republic of Korea resulting in 186 cases (including one case who travelled to China) and 39 deaths.

Overall, the reproduction number (R0) of MERS-CoV is less than 1 with significant heterogeneity in specific contexts. Specifically, outbreaks in health care settings can have R greater than 1, but they can be brought under control (R less than 1) with proper application of infection prevention and control measures and early isolation of subsequent cases.

Risk assessment
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WHO continues to work with ministries of health in all affected and at-risk countries and with international partners to better understand transmission patterns and risk factors of MERS-CoV infection in community and health care settings and to develop improved measures to prevent human infections. WHO's global risk assessment of MERS remains unchanged from the last publication, on 21 July 2017.

The continued occurrence of health care-associated outbreaks is deeply concerning and is the result of low awareness and early suspicion of MERS-CoV infections. The non-specificity of MERS symptoms complicates surveillance activities for the virus, often resulting in early missed cases, including the index case, in outbreaks and thereby providing the opportunity for human-to-human transmission in health care settings.

Investigations are ongoing to evaluate transmission within health care facilities and more comprehensive scientific studies are under way to better understand the drivers of transmission, including studies of surface and air survival and persistence. Secondary cases have reported varying levels of contact with confirmed patients, ranging from direct contact (such as health care workers providing direct care to infected patients before diagnosis with MERS) to no clear contact (such as patients sharing wards with infected patients, but without sharing health care workers or rooms). At present, it is unclear which exposures result in transmission of the virus in health care settings or what the role of environmental contamination may play in such transmissions. Several studies from the Republic of Korea have identified MERS-CoV virus on surfaces inside patient rooms and on equipment during patient stays and after discharge or death. These findings highlight the importance of adequate cleaning and disinfection of patient rooms.

WHO has updated its surveillance guidance for MERS-CoV and has specifically stated that any individuals presenting with respiratory symptoms who have recently visited the Middle East must be asked whether they have visited any health care facility there or had any direct or indirect contact with dromedary camels.

WHO stresses that it is a person's activities and exposures while in the Middle East that are relevant for MERS-CoV rather than the fact that he or she may have visited a particular country. The movement of patients between hospitals within countries and between countries for treatments and/or surgery (medical tourism) complicates the epidemiologic picture. Genetic sequencing of samples collected from confirmed patients should be a routine part of investigations into MERS-CoV clusters to better understand transmission patterns between patients and to help identify the source of the infection.

Since July 2015, WHO recommends that, in documented cases of human-to-human transmission in a health care setting, all health care contacts (such as health care workers and patients sharing space with a confirmed case), household contacts, and social contacts should be tested for MERS-CoV, regardless of whether they display symptoms. Among contacts who are at higher risk of infection are those who are in direct physical contact with the patient or the patient's biological fluids before MERS-CoV was diagnosed (such as treating physicians, health care professionals who performed intubation, cleaning staff). For these people, multiple specimens, including lower respiratory specimens whenever possible, should be collected and tested for MERS-CoV within the 14-day incubation period.

In 2018, the epidemiologic patterns of MERS-CoV remain the same: multiple introductions from dromedary camels in the Middle East to humans and secondary transmission in health care settings. Transmission among close family members within households remains limited for unclear reasons. What is different, however, is that the health care associated outbreaks in the Middle East are occurring more frequently and, often, though not always, are small in size and can affect several hospitals. The large outbreaks in Jeddah/Riyadh in 2014, in the Republic of Korea in June 2015 and in Riyadh in August 2015, remind us that MERS-CoV, if not adequately controlled, can cause explosive outbreaks with substantial socio-economic consequences.

Until zoonotic transfer of the virus from infected dromedary camels into the human population is halted, the risk remains that further health care-associated outbreaks will occur. Any health care-associated cases/clusters are concerning and more work is needed to better understand the reasons behind these outbreaks and what is necessary to prevent them. Cases have been exported to a number of countries outside of the Middle East and could happen again anywhere. The combination of factors that has previously been described illustrates that low awareness and the inability to rapidly limit exposure to MERS-CoV patients can lead to large outbreaks.

Have MERS-CoV transmission patterns changed?
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There is no evidence of sustained human-to-human transmission in the community nor is there evidence of airborne transmission as main routes of transmission from all information available from recent MERS-CoV cases.

Therefore, the overall transmission patterns previously observed remain unchanged. WHO bases this assessment on the evidence that:
1. The clinical picture seen in recent outbreaks appears to be similar to that observed throughout previous outbreaks; secondary cases in the absence of comorbidities tend to present with milder disease than primary cases; and many of the recently reported secondary cases have been mild or were in patients whose tests were positive for MERS-CoV, but were reported to be asymptomatic;

2. The cases recently exported to countries outside of the Middle East have not resulted in sustained onward transmission to persons in close contact with these cases in the community;

3. Intensive screening of MERS-CoV contacts has revealed few instances of household transmission and no transmission has been identified thus far on airplanes or other forms of transportation;

4. There has been no increase in the size or number of observed household clusters; and

5. While there is variation of the R0 number in different settings, the overall R0 of MERS-CoV is less than 1. The R0 can be higher in health care settings, as has been seen in several health care associated outbreaks in Saudi Arabia and the Republic of Korea. Experiences in Austria, China, Saudi Arabia, Thailand, and the United Arab Emirates, have shown that the R0 can be brought to less than 1 with early isolation of cases and adequate infection prevention and control measures.

Can we expect additional cases of MERS-CoV infection in the Middle East? Can we expect additional cases exported to other countries?
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WHO expects that additional cases of MERS-CoV infection will be reported from the Middle East and that occasional spillover will continue to occur in other countries by individuals who might acquire infection after exposure to an animal (for example, while visiting farms or markets or consuming raw dromedary products such as milk, urine) or human source (possibly in a health care setting for planned or emergency treatment).

Until more is understood about mode of transmission and risk factors for infection, cases resulting from animal to human (zoonotic) transmission will continue to occur and will eventually lead to limited community transmission within households and possibly significant health care associated outbreaks such as those seen in the Republic of Korea and Saudi Arabia. Consistent application of adequate infection prevention and control measures has been used to end transmission in previous clusters.

Investigation into the exported cases who reported performing Umrah in Saudi Arabia revealed that all of them had visited a health care facility, had come into contact with dromedary camels or had consumed raw camel products while in Saudi Arabia.

Recommendations
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A number of epidemiologic investigations into the transmission patterns of MERS-CoV have been conducted and published and more studies are planned or are under way. WHO hopes that these investigations can be shared with affected countries dealing with MERS-CoV and published quickly. The most urgent needs remain:

- a better understanding of how humans become infected from animal or environmental source(s) in the community;
- identification of risk factors for infection from humans or the environment in occupational settings and health care settings;
- and enhancement of community studies and surveillance for community-acquired pneumonia.

WHO has developed a MERS-CoV road map to address the development and implementation of MERS diagnostics, treatment and vaccines and a broader public health research agenda to address key unknowns for this virus focusing on 5 major areas of research:
1 - virus origin and characteristics,
2 - epidemiology and transmission,
3 - clinical management and infection prevention and control measures,
4 - product development and implementation, and
5 - impact of interventions and operational research.

Collaboration between human and animal health sectors in affected countries is essential to understanding the risk of transmission of MERS-CoV between animals and humans, whether there is any seasonal variation in the circulation of the virus in animals and the natural reservoir(s) of MERS-CoV. It is also important to work towards limiting the spread of infection in animal populations (through development of vaccines and better management of infected animals/herds) so as to reduce the opportunity for further human exposure.

WHO is supporting field-bases studies at the animal/human interface to evaluate the extent of spill over in countries outside of the Arabian Peninsula. These studies will be implemented in 2018-2019 and will aid in our understanding of the geographic extent of human infections.

In addition, a better understanding of transmission in health care settings, especially the exposures that result in human-to-human transmission, the potential role of asymptomatic infected health care workers and the possible role of environmental contamination, is urgently needed.

Enhancing infection prevention and control awareness and implementation measures is critical to preventing the possible spread of MERS-CoV in health care facilities. It is not always possible to identify patients with MERS-CoV infection early because some have mild or non-specific symptoms. For this reason, it is important that all health care facilities establish and implement clear triage policies for rapid screening and assessment of potential MERS-CoV cases and all cases with acute respiratory symptoms. It is also important for health care workers to apply standard precautions consistently with all patients, regardless of their diagnosis, in all work practices all of the time. Droplet precautions should be added to the standard precautions when providing care to any patient with symptoms of acute respiratory infection.

Health care facilities that provide care for patients suspected of or confirmed to be infected with MERS-CoV should take appropriate measures to decrease the risk of transmission of the virus from an infected patient to other patients, health care facility workers (medical and service personnel) and visitors. These measures involve interventions at the patient care interface and other general measures such as linen management, cleaning and disinfection and waste management. Contact precautions and eye protection should be added when caring for probable or confirmed cases of MERS-CoV infection and airborne precautions should be applied when performing aerosol-generating procedures. Hospital cleaning staff should also be informed of and trained to take proper precautions when cleaning rooms of MERS-CoV patients.

Until more is understood about MERS-CoV, people at high risk of developing severe disease (any person who is older, has diabetes, renal failure, chronic lung disease, or is immunocompromised), should take precautions when visiting farms or markets where dromedary camels are present (especially in the Middle East and Africa). These precautions include: avoiding contact with camels; not drinking raw camel milk or camel urine; and not eating camel meat that has not been thoroughly cooked.

Studies in Qatar, Saudi Arabia and the United Arab Emirates indicate that people handling or working with dromedary camels in these countries are at increased risk of infection with MERS-CoV compared with people who do not have contact with camels. Until more evidence is gathered, it would be prudent for camel farm workers, slaughterhouse workers, market workers, veterinarians and anyone else handling dromedary camels to practice good personal hygiene, including frequent hand hygiene. Hands should be washed with soap and water and/or alcohol gel after every contact with an animal. Workers should wear facial protection where feasible; and protective clothing, which should be removed after work (followed by hand hygiene) and washed daily.

Workers should avoid exposing family members to soiled work clothing, shoes, or other items that may have come into contact with camel secretions and excretions. These clothes and other items should remain at the workplace for daily washing and workers should have access to and use shower facilities at their workplaces before leaving the premises.

Dromedary camels infected with MERS-CoV may not show any signs of infection. It is therefore not possible to know whether an animal on a farm, in a market, at a race track or in a slaughterhouse is excreting MERS-CoV that can potentially infect humans. However, infected animals may shed MERS-CoV through nasal and eye discharge, faeces, and potentially in their milk and urine. The virus may also be found in the raw organs and meat of infected animals. Therefore, until more is known about infection in animals, the best protection is to practice good hygiene and avoid direct contact with all of these. Obviously sick animals should never be slaughtered for consumption; dead animals should be safely buried or destroyed.

Unless protected, people should avoid contact with any animal that has been confirmed positive for MERS-CoV until subsequent tests have confirmed that the animal is free of the virus.

Health officials in countries outside of the affected regions should maintain a high level of vigilance, especially those in countries with large numbers of travellers or migrant workers returning from the Middle East. Surveillance should continue to be enhanced in these countries according to WHO guidelines, along with infection prevention and control procedures in health care facilities. WHO continues to request that member states report all confirmed and probable cases along with information about their exposures, testing and clinical course to inform the most effective international preparedness and response. MERS-specific therapeutics and vaccines are in development and some clinical trials have begun. WHO through the WHO R&D Blueprint are developing clinical trial protocols to evaluate therapeutics and vaccines for MERS.

WHO does not advise special screening at points of entry with regard to MERS-CoV nor does it currently recommend the application of any travel or trade restrictions.

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communicated by:
ProMED-mail

[The above report gives a good overview of the situation from the early reports of MERS-CoV infection in 2012 through the end of June 2018 and for those tuning into MERS-CoV coverage is a good background of where we are today. Unfortunately many questions remain on the actual transmission risk factors for MERS-CoV infection. We are now 6 years into this ongoing outbreak and haven't progressed further than recognizing direct contact with camels and possibly raw camel products are a high risk factor, or visit to a health care facility.

A map showing the geographic spread of the MERS-CoV can be found at: http://www.who.int/csr/disease/coronavirus_infections/maps-epicurves/en/. - Mod.MPP]

See Also
MERS-CoV (24): Saudi Arabia, MoH reports 20180807.5950858
MERS-CoV (23): Saudi Arabia, WHO, RFI 20180711.5899938
MERS-CoV (22): Saudi Arabia, WHO 20180629.5862285
MERS-CoV (21): EMRO/WHO update May 2018 20180612.5852927
MERS-CoV (20): Saudi Arabia (NJ) susp. family cluster 20180602.5835120
MERS-CoV (19): Saudi Arabia (NJ) household cluster conf. 20180531.5830431
MERS-CoV (18): Saudi Arabia (NJ) susp. family cluster, RFI 20180530.5829389
MERS-CoV (17): UAE (Abu Dhabi) WHO 20180528.5824390
MERS-CoV (16): UAE (AZ), RFI 20180528.5823719
MERS-CoV (15): Saudi Arabia WHO 20180525.5801103
MERS-CoV (14): Israel, animal reservoir, camelids 20180506.5787312
MERS-CoV (13): Saudi Arabia new cases, superspreader 20180418.5754131
MERS-CoV (12): Saudi Arabia 20180402.5724114
MERS-CoV (11): Saudi Arabia 20180322.5702309
MERS-CoV (10): Oman, Saudi Arabia, WHO 20180315.5690014
MERS-CoV (09): Saudi Arabia, WHO 20180308.5671037
MERS-CoV (08): Saudi Arabia, RFI 20180214.5623644
MERS-CoV (07): Saudi Arabia 20180128.5590493
MERS-CoV (06): Saudi Arabia, WHO 20180126.5587442
MERS-CoV (05): Saudi Arabia 20180124.5581936
MERS-CoV (04): Saudi Arabia (RI) genomic evidence of camel role in transmission 20180116.5564064
MERS-CoV (03): Saudi Arabia, new cases, research 20180112.5556427
MERS-CoV (02): Saudi Arabia 20180109.5548385
MERS-CoV (01): Malaysia (ex KSA), Saudi Arabia, UAE (ex Oman) 20180102.5532148
2017
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MERS-CoV (77): Saudi Arabia, camels, human, epidemiology, assessment 20171222.5520561
MERS-CoV (01): Saudi Arabia (QS, RI, MD) RFI 20170105.4744802
2016
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MERS-CoV (123): Saudi Arabia (MK, AS) new cases 20161231.4734758
MERS-COV (01): Oman, Saudi Arabia 20160105.3911188
2015
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MERS-COV (167): acute management and long-term survival 20151231.3904300
MERS-CoV (01): Saudi Arabia, new cases, new death 20150104.3069383
2014
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MERS-CoV (69): Saudi Arabia, new case, RFI 20141230.306305
MERS-CoV (01): Bangladesh, KSA, Algeria, UAE, Iran, WHO, RFI 20140616.2541707
MERS-CoV - Eastern Mediterranean (82): anim res, camel, seroepidemiology 20140613.2537848
MERS-CoV - Eastern Mediterranean (01): Saudi Arabia, UAE, Oman, WHO 20140103.2150717
2013
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MERS-CoV - Eastern Mediterranean (106): animal reservoir, camel, Qatar, OIE 20131231.2145606
MERS-CoV - Eastern Mediterranean: Saudi Arabia, new case, RFI 20130518.1721601
Novel coronavirus - Eastern Mediterranean (29): MERS-CoV, ICTV nomenclature 20130516.1717833
Novel coronavirus - Eastern Mediterranean: bat reservoir 20130122.1508656
2012
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Novel coronavirus - Eastern Mediterranean (06): comments 20121225.1468821
Novel coronavirus - Eastern Mediterranean: WHO, Jordan, conf., RFI 20121130.1432498
Novel coronavirus - Saudi Arabia (18): WHO, new cases, cluster 20121123.1421664
Novel coronavirus - Saudi Arabia: human isolate 20120920.1302733
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