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Novel coronavirus infection - update
23.11.2012 - WHO

WHO has been notified of four additional cases, including one death, due to infection with the novel coronavirus. The additional cases have been identified as part of the enhanced surveillance in Saudi Arabia (3 cases, including 1 death) and Qatar (1 case). This brings the total of laboratory confirmed cases to 6.

Investigations are ongoing in areas of epidemiology, clinical management, and virology, to look into the likely source of infection, the route of exposure, and the possibility of human-to-human transmission of the virus. Close contacts of the recently confirmed cases are being identified and followed-up.

So far, only the two most recently confirmed cases in Saudi Arabia are epidemiologically linked - they are from the same family, living in the same household. Preliminary investigations indicate that these 2 cases presented with similar symptoms of illness. One died and the other recovered.

Additionally, 2 other members of this family presented with similar symptoms of illness, where one died and the other is recovering. Laboratory results of the fatal case is pending, while the case that is recovering tested negative for the novel coronavirus.

WHO continues to work with the governments of Saudi Arabia, Qatar and other international health partners to gain a better understanding of the novel coronavirus and the disease in humans. Further epidemiological and scientific studies are needed to better understand the virus.

WHO encourages all Member States to continue their surveillance for severe acute respiratory infections (SARI) and is currently reviewing the case definition and other guidance related to the novel coronavirus. Until more information is available, it is prudent to consider that the virus is likely more widely distributed than just the two countries which have identified cases. Member States should consider testing of patients with unexplained pneumonias for the new coronavirus even in the absence of travel or other associations with the two affected countries. In addition, any clusters of SARI or SARI in health care workers should be thoroughly investigated regardless of where in the world they occur.

Of the 6 laboratory confirmed cases reported to WHO, 4 cases (including 2 deaths) are from Saudi Arabia and 2 cases are from Qatar.

Gruß
Birgitt

NOVEL CORONAVIRUS - EASTERN MEDITERRANEAN: WHO, JORDAN, APRIL 2012, CONFIRMED, REQUEST FOR INFORMATION
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In this update:
[1] WHO GAR report - Jordan April 2012
[2] WHO summary of nCoV as of 30 Nov 2012



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[1] WHO GAR report - Jordan April 2012

Date: 30 Nov 2012
Source: WHO GAR
http://www.who.int/csr/don/2012_11_30/en/index.html


Novel coronavirus infection - update [30 Nov 2012]
---------------------
In addition to the fatal case of novel coronavirus in Saudi Arabia reported to WHO on [28 Nov 2012], 2 fatal cases in Jordan have been reported to WHO today, bringing the total of laboratory-confirmed cases to 9.

The latest confirmed case from Saudi Arabia occurred in October 2012 and is from the family cluster of the 2 cases confirmed earlier.

The 2 cases from Jordan occurred in April 2012. At that time, a number of severe pneumonia cases occurred in the country and the Ministry of Health (MOH) Jordan promptly requested a WHO Collaborating Centre for Emerging and Re-emerging Infectious Diseases (NAMRU - 3) team to immediately assist in the laboratory investigation. The NAMRU-3 team went to Jordan and tested samples from this cluster of cases.

On [24 Apr 2012] the NAMRU-3 team informed the MOH that all samples had tested negative for known coronaviruses and other respiratory viruses. As the novel coronavirus had not yet been discovered, no specific tests for it were available.

In October 2012, after the discovery of the novel coronavirus, stored samples were sent by MOH Jordan to NAMRU-3. In November 2012 NAMRU-3 provided laboratory results that confirmed 2 cases of infection with the novel coronavirus.

The MOH Jordan has requested WHO assistance in investigating these infections. A mission from WHO Eastern Mediterranean Regional Office (EMRO) and headquarters arrived in Amman on 28 November 2012 to assist in further epidemiological surveillance and to strengthen the sentinel surveillance systems for severe acute respiratory infections (SARIs).

In summary, to date a total of 9 laboratory-confirmed cases of infection with the novel coronavirus have been reported to WHO - 5 cases (including 3 deaths) from Saudi Arabia, 2 cases from Qatar and 2 cases (both fatal) from Jordan.

--
Communicated by:
ProMED-mail Rapporteur Marianne Hopp

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[2] WHO summary of nCoV as of 30 Nov 2012
Date: 30 Nov 2012
Source: WHO GAR
http://www.who.int/csr/disease/coronavi ... index.html


Background and summary of novel coronavirus infection - as of [30 Nov 2012]
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Over the past 2 months, WHO has received reports of 9 cases of human infection with a novel coronavirus. Coronaviruses are a large family of viruses; different members of this family cause illness in humans and animals. In humans, these illnesses range from the common cold to infection with Severe Acute Respiratory Syndrome (SARS) coronavirus (SARS CoV).

Thus far, the cases reported have come from Qatar, Saudi Arabia and Jordan. All patients were severely ill, and 5 have died.

The 2 Qatari patients are not linked. Both had severe pneumonia and acute renal failure. Both are now recovering.

A total of 5 confirmed cases have been reported from Saudi Arabia. The 1st 2 are not linked to each other; one of these has died. Three other confirmed cases are epidemiologically linked and occurred in one family living within the same household; 2 of these have died. One additional family member in this household also became ill, with symptoms similar to those of the confirmed cases. This person has recovered and tested negative, by polymerase chain reaction (PCR) tests, for the virus.

Two confirmed cases have been reported in Jordan. Both of these patients have died. These cases were discovered through testing of stored samples from a cluster of pneumonia cases that occurred in April 2012.

The 2 clusters (Saudi Arabia, Jordan) raise the possibility of limited human-to-human transmission or, alternatively, exposure to a common source. Ongoing investigation may or may not be able to distinguish between these possibilities.

The current understanding of this novel virus is that it can cause a severe, acute respiratory infection presenting as pneumonia. Acute renal failure has also occurred in 5 cases.

WHO recognizes that the emergence of a new coronavirus capable of causing severe disease raises concerns because of experience with SARS. Although this novel coronavirus is distantly related to the SARS CoV, they are different. Based on current information, it does not appear to transmit easily between people, unlike the SARS virus.

WHO has closely monitored the situation since detection of the 1st case and has been working with partners to ensure a high degree of preparedness should the new virus be found to be sufficiently transmissible to cause community outbreaks. Some viruses are able to cause limited human-to-human transmission under condition of close contact, as occurs in families, but are not transmissible enough to cause larger community outbreaks. Actions taken by WHO in coordination with national authorities and technical partners include the following:

Investigations are ongoing to determine the likely source of infection and the route of exposure. Close contacts of confirmed cases are being identified and followed up.
An interim surveillance recommendation has been updated to assist clinicians to determine which patients should undergo laboratory testing for the presence of novel coronavirus.

Laboratory assays for the virus have been developed. Reagents and other materials for testing are available, as are protocols, algorithms and reference laboratory services. WHO has activated its laboratory network to assist in testing and other services. WHO has also issued preliminary guidance for laboratory biorisk management.
Guidance is available for infection control.

Based on the current situation and available information:

- WHO encourages all Member States to continue their surveillance for severe acute respiratory infections (SARI) and to carefully review any unusual patterns.
Further, testing for the new coronavirus of patients with unexplained pneumonias should be considered, especially in persons residing in or returning from the Arabian peninsula and neighboring countries. Any new cases should be promptly reported both to national health authorities and to WHO.

- In addition, any clusters of SARI or SARI in health care workers should be thoroughly investigated, regardless of where in the world they occur. These investigations will help determine whether the virus is distributed more widely in the human population beyond the 3 countries that have identified cases.

- WHO does not advise special screening at points of entry with regard to this event nor does it recommend that any travel or trade restrictions be applied.

- WHO continues to work with Member States and international health partners to gain a better understanding of the novel coronavirus and the disease in humans and will continue to provide updated information. As the situation evolves, WHO will reassess its guidance and revise it accordingly.

--
Communicated by:
ProMED-mail
<promed@promedmail.org>

[The above WHO report now increases the official number of laboratory confirmed cases of severe acute respiratory illness (SARI) due to infection with the novel coronavirus (nCoV) to 9, with 5 fatalities.

In a prior ProMED-mail report on this nCoV, Dr. Irene Lai had reported on an as yet undiagnosed outbreak of SARI in Jordan, querying if that outbreak would be reviewed to see if perhaps this nCoV was the etiology of the outbreak.

Information available at that time came from an ECDC report from May 2012 available at http://ecdc.europa.eu/en/publications/P ... 202012.pdf:

"Severe respiratory disease of unknown origin - Jordan - Outbreak in ICU
Opening date: 26 April 2012 Latest update: 3 May 2012

An outbreak of a respiratory illness was reported on 19 April 2012 by the Ministry of Health in Jordan in an intensive care unit in a hospital in Zarqa. Seven nurses and one doctor were among the 11 affected. One of the nurses died. The cause of this
outbreak remains unknown to date."

From the above reports it appears as though the outbreak in Jordan in April 2012 was due to this nCoV, and most likely does represent limited human-to-human transmission -- involving the ICU healthcare personnel caring for a patient with SARI. With respect to the family cluster reported in Saudi Arabia, more information on the epidemiology of this outbreak including dates of onsets of cases, locations of contact between the family members (were they all from a common household, were any caretakers for earlier onset illness cases) might help in ascertaining if that cluster involved person-to-person transmission or if there had been a common source exposure in the household setting.

More information on results of testing of the other members of this cluster of cases in Jordan would be greatly appreciated. If the recovered cases are negative through currently available laboratory tests, it would add to an observation that milder cases are not "detected" through the currently available laboratory techniques.

If one looks at a map of the region (see the HealthMap/ProMED map available at: http://healthmap.org/r/1HAJ) one sees that Saudi Arabia shares a border with Jordan to the Northwest and Qatar to the Southeast. - Mod.MPP]

NOVEL CORONAVIRUS - EASTERN MEDITERRANEAN (02): DIAGNOSTICS
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[1]
Date: Wed 5 Dec 2012
Source: Eurosurveillance Edition 2012, 17(49) [summ., edited]
http://www.eurosurveillance.org/ViewArt ... leId=20335


Laboratory capability for molecular detection and confirmation of novel coronavirus in Europe, November 2012
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[Authors: Palm D, Pereyaslov D, Vaz J, Broberg E, Zeller H, Gross D, Brown CS, Struelens MJ, on behalf of the Joint ECDC-WHO Regional Office for Europe Novel Coronavirus Laboratory Survey participants; ECDC National Microbiology Focal Points, WHO European Region EuroFlu Network and European Network for Diagnostics of "Imported" Viral Diseases (ENIVD)]

Summary
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A rapid survey by the European Centre for Disease Prevention and Control (ECDC) and the World Health Organization (WHO) Regional Office for Europe ascertained the availability of national reference laboratory testing for a recently detected novel coronavirus as of 28 Nov 2012. Screening by internal quality controlled upE [upstream from the E gene]-RT-PCR assay was available in 23/46 of responding countries in the WHO European Region, of which 19/30 in European Union (EU) and European Economic Area (EEA) countries. Confirmation of positive screened samples by either 1b [open reading frame 1b]- RT-PCR, or other target RT-PCR assays with sequence analysis or whole-genome sequence analysis was available in 22/46 responding countries of which 18/30 in EU/EEA countries.

Background
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In September 2012, a novel coronavirus was first characterised by genome sequencing at the Erasmus Medical Center (EMC) of a viral isolate from a patient in Saudi Arabia with severe pneumonia [1-2]. This virus belongs to the genus _Beta-coronavirus_ and is closely related to some bat coronaviruses. Since then, a total of 9 confirmed cases of human infection with the novel coronavirus have been reported to public health authorities and WHO [3-6]. These patients developed a severe respiratory disease in Saudi Arabia, Qatar, and Jordan over the period April to November 2012 and 5 had a fatal outcome [1-6]. 2 patients were referred to Europe for specialised care [1-6].

Coronaviruses are membrane enveloped viruses with large RNA genomes and a distinctive surface crown [hence 'corona' - Mod.CP] causing respiratory and enteric infections in humans and animals. In 2003, zoonotic transmission of SARS-CoV caused a worldwide epidemic associated with more than 8000 cases of severe acute respiratory syndrome (SARS) and a case-fatality rate of 10 percent [7].

Monitoring of novel coronavirus
-------------------------------
While the reservoir and mode of transmission of the novel coronavirus virus are under investigation, WHO and ECDC [European Centre for Disease Prevention and Control] request that any probable or confirmed case that is diagnosed should rapidly (i) be reported to national authorities to enable them to take appropriate public health measures, and (ii) be notified to WHO under the International Health Regulations (2005) and simultaneously through joint reporting system to the Early Warning and Response System (EWRS) for countries in the EU/EEA [3,4,8].

In September 2012, Corman et al described the 1st diagnostic assays for the novel coronavirus [9]. These involve a 2-step screening and confirmation testing algorithm using newly developed specific RT-PCR assays that target the regions upstream of the E [envelope] gene (the upE target; recommended for screening) and open reading frame 1b [polymerase gene] (ORF1b; recommended for confirmation) [9]. Additional testing based on sequence analysis of other viral genome targets or whole genome sequence determination from clinical material or culture isolate can also be used to confirm cases [2,6].

A number of pan-coronavirus RT-PCR assays have been described which target the polymerase gene of coronaviruses used for the detection of known and unknown coronaviruses, including coronaviruses currently circulating in humans such as hCoV-229E, hCoV-NL63, hCoV-OC43, and SARS-CoV [10-12]. Some of these pan-coronavirus RT-PCR assays may be also used to detect the novel coronavirus. However, a positive result should be confirmed by screening for the specific targets described for hCoV-EMC, sequencing of the RT-PCR product and/or virus isolation [1,2,6].

The rapid communication of technical protocols of validated diagnostic assays and distribution of positive RNA control material is essential to provide public health laboratories with the means to screen and confirm cases of this emerging viral disease and allow for appropriate public health response [4,8,13]. WHO is developing laboratory testing guidance on the detection of the novel coronavirus. To obtain background information for the updated guidance and to identify the needs for support by ECDC and WHO Regional Office for Europe to virology laboratories for case ascertainment across Europe, the capability of national laboratories was jointly investigated by questionnaire surveys.

Survey on novel coronavirus detection capabilities
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Two coordinated surveys were administered by email from ECDC and the WHO Regional Office. The ECDC survey was sent to the National Microbiology Focal Points of the 30 EU/EEA countries and in the EU accession country Croatia and to contact points for laboratories in the European Network for Diagnostics of "Imported" Viral Diseases (ENIVD) [14], on 26 Nov 2012. The Regional Office survey was sent to EuroFlu National Focal Points in 53 countries in the WHO European Region on 26 Nov 2012, with a deadline set for 29 Nov 2012. Reminders were sent to the networks after 29 Nov 2012 and an additional 10 replies, received by 3 Dec 2012, were included in this report.

The ECDC survey questions covered 5 areas: national laboratories involved in testing for novel coronavirus, availability of laboratory tests and positive controls, laboratory tests under development, sampling strategy and test referral, and need for support. The Regional Office survey questions covered the following areas: confirmation if the WHO-recognised National Influenza Centre (NIC) or other laboratory serve as national reference laboratory for novel coronavirus testing, availability of laboratory tests and positive controls, and need for support.

Data were validated with request for clarification by the survey respondents on 3 Dec 2012 and confirmed data were received by 4 Dec 2012. Hereafter data from both surveys were merged, duplicate responses removed and validated data analysed jointly by ECDC and Regional Office.

Survey results
--------------
The response rates were 93 percent (28/30 countries) for the EU/EEA countries included in the ECDC survey and 76 percent (40/53 countries) for the WHO Regional Office survey; taken together, the surveys captured data from 46/53 of WHO European Region Member States and all EU/EEA countries. In total, information was provided by 47 countries responding to one or both questionnaires.

The results [available by accessing the original text of this document via the source URL above] indicate which molecular tests were available for novel coronavirus detection and confirmation at national reference or expert laboratory level at the time of the survey. According to recommendations [9,14] screening by internal quality controlled upE- RT-PCR assay was available in 23/46 of responding WHO European Region countries and 19/30 EU/EEA countries. Confirmation of positive screened samples by either ORF1b-RT-PCR, other target RT-PCR assays with sequence analysis or whole genome sequence analysis was available in 18/30 EU/EEA countries and in 22/46 responding WHO European Region countries. [Illustrated by a figure in the original text, available at the source URL above]. The figure indicates the level of screening and confirmation assays available in the 47 responding countries, including 46 WHO European Region Member States, 27 EU Member States, and 3 EEA countries, 2 of which are also Member States of WHO European Region.

Many countries indicated that their reference laboratories were developing specific molecular detection tests, serological assays, or were awaiting positive RNA control material for RT-PCR assays. Therefore, it should be emphasised that the results presented here are an overview of laboratory tests in operation at the time of survey and will require updating as capacities are rapidly increasing in the participating countries.

In 25 countries, the NIC [WHO-recognised National Influenza Centre] reported to be the national reference laboratory for novel coronavirus and in 17 of these countries it was the only laboratory reporting diagnostic capability. In 10 countries, more than one laboratory was reported to perform novel coronavirus diagnostic tests at national or regional levels. 20 laboratories that reported diagnostic capability from 12 countries were members of ENIVD. 12 of 25 countries with no confirmation capacity at national level reported referral arrangements to ship samples for testing in another country.

Of note, laboratories in 6 EU/EEA countries indicated that samples had been tested to date for novel coronavirus from approximately 250 patients fulfilling the WHO definition patients under investigation. Of the 9 cases reported so far to WHO from Saudi Arabia, Qatar, and Jordan, in addition to in-country testing, 3 have been tested and confirmed by the Erasmus Medical Centre, Rotterdam, the Netherlands, the Health Protection Agency, London, United Kingdom, and the Robert Koch Institute, Berlin, Germany [2,5,6].

Conclusions
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The findings of this study indicate an extensive deployment of newly developed novel coronavirus molecular detection assays among public health reference and expert virology laboratories in Europe within only 2 months after sequence information on the 1st reported case was made available. This deployment occurred to a greater extent in EU/EEA countries of the WHO European Region compared with south-east and eastern European countries. Screening tests were available in nearly half of countries of the WHO European Region and cross-border shipment arrangements were in place in many of those lacking domestic testing capacity.

Our results will allow virologists and public health agencies, including ECDC and the WHO Regional Office, to remedy gaps within their laboratory networks. Such measures may include technical laboratory guidance and collaborative arrangements for cross-border referral testing of clinical materials, technical support such as distribution of reference control materials, assistance with development of quality controlled serological assays and, if warranted in the longer term, provision of capacity building courses and external quality assessment schemes.

--
Communicated by:
ProMED-mail
<promed@promedmail.org>

[The complete list of references is available at the source URL above. - Sr.Tech.Ed.MJ]

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[2]
Date: Thu 6 Dec 2012
Source: Eurosurveillance Edition 2012, 17(49) [summ., edited]
http://www.eurosurveillance.org/ViewArt ... leId=20334


Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections
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[Authors: Corman VM, Mueller MA, Costabel U, Timm J, Binger T, Meyer B, Kreher P, Lattwein E, Eschbach-Bludau M, Nitsche A, Bleicker T, Landt O, Schweiger B, Drexler JF, Osterhaus AD, Haagmans BL, Dittmer U, Bonin F, Wolff T, Drosten C. Eurosurveillance, Volume 17, Issue 49]

Background
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We present a rigorously validated and highly sensitive confirmatory real-time RT-PCR assay (1A assay) that can be used in combination with the previously reported upE assay. 2 additional RT-PCR assays for sequencing are described, targeting the RdRp gene (RdRpSeqassay) and N gene (NSeq assay), where an insertion/deletion polymorphism might exist among different hCoV-EMC strains [that is, isolates of other hCoV-EMC [human Erasmus Medical Centre-like coronaviruses not associated with respiratory disease. - Mod.CP]. Finally, a simplified and biologically safe protocol for detection of antibody response by immunofluorescence microscopy was developed using convalescent patient serum.

A novel human coronavirus, hCoV-EMC, has recently emerged in the Middle East region [1-3]. The virus has caused severe acute respiratory infection (SARI) in at least 9 patients to date. Latest reports from the World Health Organization (WHO) suggest that infections have occurred since April 2012, as hCoV-EMC was found retrospectively in 2 patients from a group of 11 epidemiologically linked cases of SARI in Jordan, 8 of whom were healthcare workers [4].

We have recently presented methods for the rapid detection of hCoV-EMC by real-time reverse transcription polymerase chain reaction (RT-PCR) [2]. One of these protocols, the upE gene assay, has been used as a first-line diagnostic assay for all human cases to date. More than 100 laboratories worldwide have since been equipped with positive-control material necessary to conduct the upE assay. We also presented a confirmatory RT-PCR assay targeting the open reading frame (ORF) 1b gene, with slightly lower sensitivity than the upE assay.

In view of the growing knowledge of the epidemiology of hCoV-EMC infections, WHO is continuously updating its guidelines for laboratory testing. During an expert consultation on 28 Nov 2012, it was concluded that first-line screening should involve the upE assay [2]. Confirmatory testing can involve any appropriately validated RT-PCR assay for alternative targets within the viral genome, followed by sequencing of at least a portion of one viral gene that can then be compared with hCoV-EMC sequences deposited in GenBank.

Recent investigations into a cluster of cases in Saudi Arabia have revealed the possibility that the virus may not be detected by RT-PCR in all patients with symptoms and proven epidemiological linkage [5]. From our previous experience during the severe acute respiratory syndrome (SARS) epidemic in 2003, such issues were predicted to occur when testing by RT-PCR alone [2]. In SARS patients, in particular those seen more than 10 days after symptom onset, serological testing by immunofluorescence assay (IFA) has been successfully used to complement RT-PCR findings [6,7].

On 22 Nov 2012, German health authorities were notified of a patient who had been treated for SARI in a hospital in Essen, Germany [5]. On the basis of clinical samples from this case, we present here a set of validated assays for the confirmation of cases of hCoV-EMC infection, including a confirmatory real-time RT-PCR assay in the ORF1a gene, 2 sequencing amplicons in the RNA-dependent RNA polymerase (RdRp) and nucleocapsid (N) protein genes, as well as a straightforward methodology for biologically safe immunofluorescence testing.

[The complete text of this communication describes these assays and interested readers are referred to the original source URL above to obtain details of these tests and experimental protocols. - Mod.CP]

Discussion
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Here we present nucleic acid-based and serological assays for the confirmation of hCoV-EMC infections. The current strategy and recommendations by WHO require reference laboratories to be involved in cases where 1st-line screening has provided positive results. However, with the potential occurrence of more cases of hCoV-EMC infection, the demand for confirmatory testing might grow in a way that it could overwhelm the capacity of reference laboratories. The major challenge in setting up confirmatory methodology will be the validation of tests. Technical studies can be tedious and clinical validation is hard to achieve if no patient samples are at hand. The documentation here of proven methodology is presented with those laboratories in mind that will have to provide diagnostic testing and additional reference services in the future, but cannot rely on their own validation studies.

For the augmentation of confirmatory testing by serology, IFA, ideally in paired sera taken several days apart, proved highly robust during the SARS epidemic [6,7]. In contrast to EIA [enzyme immunoassay], IFA provides additional criteria for result interpretation via the localisation of signals within cells. False-positive reactivity can thus be circumvented. The data presented here are intended as reference for those laboratories willing to confirm cases of hCoV-EMC infection by IFA. We have shown in this single patient that antibodies were detectable by IFA at a time when the patient still presented severe disease and the virus was not yet eliminated from respiratory secretions as detectable by RT-PCR (case report to be presented elsewhere). As in many SARS patients, the antibody titre was in the medium range, below 1:1000, even in convalescence [6]. In SARS patients, IFA seroconversions usually began to show from day 10 of symptoms onward, while virus RNA could not be detected by RT-PCR in respiratory secretions starting from day 15 onward [6,7].

It is important to mention that IFA slides contain virus-infected cells which in theory could retain infectious virus. However, it has been shown in a meticulous investigation of SARS-CoV that acetone fixation of IFA slides results in the reduction of infectivity to undetectable levels. The extent of reduction of infectivity was at least 6.55 log 10 infectious virus doses [9] (greater reductions could not be measured by the assay applied). In the rapid and biologically safe IFA procedure we presented here, further reduction of any conceivable residues of infectivity was achieved by combining acetone fixation with paraformaldehyde treatment. This treatment was shown to confer efficient reduction on SARS-CoV [9] and is also effective against other enveloped RNA viruses [13]. No residual infectivity should exist in the rapid and biologically safe IFA slides described here.

We have also shown that there is good correlation between IFA results and western blot against the 2 major structural proteins, S and N. Western blotting might therefore be an option as a confirmatory diagnostic for serology. However, in absence of data from a considerably larger number of patients, care must be taken in interpreting the results from western blot alone, as SARS patients were found to vary in their immune responses against single proteins in western blot [14,15]. Not only western blot but also neutralisation tests should be evaluated for their capacity to afford a highly specific confirmation of serological results [7]. This is of particular importance because it is unknown to what extent hCoV-EMC antibodies cross-react with those against common human coronaviruses such as OC43 and HKU1. In the present study, we have not investigated cross-reactivity in a larger group of patients, as this requires meticulous counter-testing and selection of samples with high titres against other human coronaviruses, as well as confirmation by additional methods such as differential virus neutralisation tests. The serological data presented here should be regarded as suggestions for confirmatory testing of epidemiologically linked individuals, or of cases under investigation due to positive results in first-line tests.

--
Communicated by:
ProMED-mail
<promed@promedmail.org>

[The complete list of references is available at the source URLs above. - Sr.Tech.Ed.MJ]

[The 1st document is an inventory of the current capability of European diagnostic laboratories to reliably identify the novel coronavirus responsible for the recent ARI cases in the Eastern Mediterranean, and to distinguish it from other human coronaviruses recently in circulation and associated with mild or no human respiratory disease. Interested readers should consult the original text via the source URL to view the data and references cited in the complete text.

In the 2nd document above the authors start with the observe that recent investigations into a cluster of cases in Saudi Arabia have revealed the possibility that the virus may not be detected by RT-PCR in all patients with symptoms and proven epidemiological linkage. The paper then deals with refinement of existing diagnostic methodology and provides descriptions of new methodologies.

The essential message is that in absence of data from a wide range of patients reliance on a single diagnostic procedure can be unreliable. For example in the SARS outbreak it was observed that a considerably larger number of patients SARS patients were found to vary in their immune responses against single proteins in Western blot analyses. Likewise neutralisation tests should be evaluated for their capacity to afford a highly specific confirmation of serological result. This is of particular importance because it is unknown to what extent hCoV-EMC antibodies cross-react with those against common human coronaviruses such as OC43 and HKU1. In the present study, they have not investigated cross-reactivity in a larger group of patients, as this requires meticulous counter-testing and selection of samples with high titres against other human coronaviruses, as well as confirmation by additional methods such as differential virus neutralisation tests. The serological data presented here should be regarded as suggestions for confirmatory testing of epidemiologically linked individuals, or of cases under investigation due to positive results in first-line tests.

Interested readers should access the original text via the source URL to obtain details of the updated molecular and serological methodologies. - Mod.CP]

NOVEL CORONAVIRUS - EASTERN MEDITERRANEAN (03): PROPOSALS FOR A RESEARCH AGENDA, INTERNATIONAL SEVERE ACUTE RESPIRATORY AND EMERGING INFECTION CONSORTIUM (ISARIC)
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Date: Sat 8 Dec 2012 17:45:09 +0000
From: Kajsa-Stina Magnusson [edited]
<kajsa-stina.magnusson@ndm.ox.ac.uk>


Subject: Novel coronavirus -- Proposals for a research agenda ISARIC (UK)
-------------------------------------------------------------------------
Clinical research needs for patients infected with the Novel Coronavirus -- Proposals from the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC)

8 Dec 2012
In light of the recent WHO update on the Novel Coronavirus [30 Nov 2012] (http://www.who.int/csr/disease/coronavi ... index.html), and given the paucity of evidence on which to base treatment and understand disease pathogenesis, ISARIC -- a recently formed global clinical research consortium -- would like to propose a collaborative clinical research platform. The proposed studies aim to assess prospectively the pathogenesis of illness and potential therapeutic interventions for patients infected with the novel coronavirus (nCoV). Standardized collection of data will facilitate sharing of information among those caring for such patients. The proposals from ISARIC would be open and available to any organization interested in participating.

Though the total number of laboratory confirmed cases to date is low, it is impossible to know how many cases may occur. In addition the patients may be admitted in future to multiple hospitals in many different countries. It is crucial to plan for standardized, prospective data collection in order to understand how to improve the clinical outcome for patients with nCoV. The following suggestions also cover specific therapeutic interventions, which we believe need to be evaluated. These interventions do not include studies on supportive care such as access to critical care, fluid management and organ support as established guidelines, including those of WHO, are available for these.

ISARIC proposed studies
Observational studies should be conducted in the situation of a novel disease, which may occur in a variety of resource settings, and may be the only pragmatic option for data collection available. Clinicians should include data collection on all therapeutic interventions delivered.

Prospective, sequential, standardized clinical data collection and daily sampling for virological and pathogenesis studies should be undertaken, whenever feasible, and with strict adherence to appropriate infection control measures. Where possible we recommend that these clinical samples should be stored, with consent, for future research.

In the absence of evidence to guide treatment we would suggest interventions are delivered as part of a randomized clinical trial (see below). However, we recognize that this may not be possible.

We propose a pragmatic framework in which research protocols developed in different parts of the world may produce results suitable for future collaborative analysis (see full table and diagram: http://isaric.tghn.org/articles/novel-c ... ling-plan/). In producing this proposal, we assign the highest priority to research questions that will provide information that is immediately clinically relevant. Local resource requirement to recruit cases is the primary determinant of which hospitals can participate. In practice this is the key determinant of the global spread of a research project, and hence the number of cases that can be recruited. We therefore used the local resource requirement to stratify studies: studies on the lowest tier (tier 1, Tiered Strategy: http://isaric.tghn.org/articles/novel-c ... ling-plan/) may be carried out in almost any hospital that is capable of participating in research, whereas some studies in tier 3 require extensive dedicated research staff in any recruiting centre.

Tiers 1 plus 2 comprise samples and data for studies that both require large numbers of cases but have relatively limited local resource implications. Full recruitment to these studies would require:

1. Consent
2. Storage of all clinically-indicated pathogen samples
3. A single EDTA blood sample at the time of recruitment, to be split into plasma and cell fractions locally.

Tier 3 lists additional studies, all of which are to some extent dependent on Tiers 1 plus 2. A more detailed list of samples proposed in this tier is available for download on ISARIC=92s website: http://isaric.tghn.org/articles/novel-c ... ling-plan/).

Randomized Controlled Trials (RCTs) could be initiated either if sufficient patients are seen at one location or via a collaborative regional or global effort with appropriate ethical approvals in place. Therefore, we suggest that clinicians and researchers consider, in advance, which intervention(s) they would with to evaluate in an RCT and have pre-emptive discussions with ethics committees to expedite decision-making.

Please see the discussion below with our suggestions regarding the therapeutic interventions that could be studied.

We will make available online at http://www.isaric.org/ a draft consent form, case report form and outline protocol (adaptable) for anyone either interested in participating in such a collaborative effort or requiring access to these materials for their own use in individual studies.

Potential therapeutic interventions
No antivirals or therapeutics of proven value currently exist for the novel CoV, and insufficient data were generated in studies of patients with the SARS-CoV to be able to guide treatment decisions (Wong and Yuen, J Antimicrob Chem 2008, 62:437; Stockman et al., PLoS Med 2006, 3(9): e343). However, a potential role for antiviral therapy is supported by the observation that viral load is positively correlated with the development of organ dysfunction and death in SARS-CoV patients (Hung IF et al. Emerg Infect Dis 2004, 10:1550). Based on rhesus macaque model and/or clinical studies in SARS, antiviral agents of particular interest would include Interferon-alfa (Loutfy et al., JAMA 2003, 290:3222), neutralizing antibody (convalescent plasma or monoclonal antibodies if/when available) (Yeh et al., JAC 2005, 56:919), and perhaps siRNAs (Li et al., Nature Med 2005, 11:944). Neither systemic ribavirin nor HIV protease inhibitors (lopinavir-ritonavir) were proven beneficial in SARS, and ribavirin was associated with significant side effects. However, the use of lopinavir/ritonavir plus ribavirin was associated with a lower incidence of adverse outcomes including acute respiratory distress syndrome, other adverse outcomes and death and antiviral effects when compared with historical controls who had received ribavirin alone (Chu CM et al., Thorax 2004, 59:252), so that further study appears warranted. Unlike SARS CoV, the nCov does not appear to share the ACE2 receptor (R Fouchier, personal communication), so that inhibitors directed to it are unlikely to be effective. The finding that mannose-binding lectin (MBL) levels were lower in SARS patients (Ip et al., JID 2005, 191:1697) and that MBL can inhibit the SARS-CoV in vitro (Zhou et al., J Virol 2010, 84(17):8753), raise the possibility of using recombinant human MBL, shown active in an Ebola murine model (Michelow et al., JID 2011, 203:175), for treatment.

The role of immunomodulatory interventions in SARS treatment remains unclear. Systemic corticosteroids were commonly used in SARS patients and, while some reports suggested transient effects on fever and pulmonary manifestations, no survival benefit was established and serious adverse effects include increased risk of secondary infections and aseptic necrosis of the hip. The use of corticosteroids was also associated with an increase in the plasma viral load (Lee N et al., J Clin Virol 2004, 31: 304=969). IVIg was not systematically studied in SARS but may warrant further study for both its immunomodulatory effects and possible nCoV inhibitory activity. There is continued interest in the role of statins and other immunomodulatory agents in severe acute respiratory infections in general and these could be considered as part of detailed observational studies or ideally an RCT.

About ISARIC
The International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) is a global consortium of clinical research networks aiming to change the approach to collaborative patient orientated research between and during rapidly emerging public health threats. A new approach will enable the generation and sharing of new knowledge, complement public health responses, maximize the availability of clinical information and thereby save lives. Being a partner of ISARIC is open to anyone interested in clinical research in rapidly emerging public health threats globally.

We hope that ISARIC, supported by, the Wellcome Trust, Medical Research Council UK, Bill and Melinda Gates Foundation, INSERM France, Singapore Ministry of Health, and the Li Ka Shing Foundation will help facilitate collaborative patient orientated research to complement the public health response in epidemics and pandemics.

http://www.wellcome.ac.uk/News/Media-of ... 053638.htm
<www.isaric.orghttp://www.isaric.org/

Signed the ISARIC Executive, through:
Derek Angus
University of Pittsburgh School of Medicine, USA

Kenneth Baillie
The Roslin Institute, University of Edinburgh, UK

Roberto Bruzzone
HKU-Pasteur Research Pole, University of Hong Kong, Hong Kong SAR

Dean Everett
Malawi-Liverpool-Wellcome Trust Clinical Research Programme & University of Liverpool, Malawi

Jeremy Farrar, Chairman ISARIC
Oxford University Clinical Research Unit Hospital for Tropical Diseases Vietnam
Wellcome Trust Programme Vietnam South East Asian Infectious Disease Clinical Research Network (SEAICRN)

Gail Carson
International Severe Acute Respiratory and Emerging Infection Consortium and University of Oxford UK
Zhancheng Gao
Peking University People's Hospital, China
Frederick Hayden
Wellcome Trust, London UK and University of Virginia School of Medicine, Charlottesville, Virginia, USA

John Marshall
University of Toronto, CCCTG & InFACT, Canada
Gernot Rohde
Maastricht University, The Netherlands

Kathy Rowan
ICNARC, UK

Steve Webb
University of Western Australia, Australia

Please contact Kajsa-Stina Magnusson, ISARIC project manager with any questions at <kajsa-stina.magnusson@ndm.ox.ac.uk>

--
Kajsa-Stina Magnusson
ISARIC Project Manager
University of Oxford
Centre for Tropical Medicine (CCVTM)
Nuffield Department of Medicine
Churchill Hospital
Old Road
Oxford
OX3 7LJ
UK
<kajsa-stina.magnusson@ndm.ox.ac.uk>

Learn more about ISARIC at: http://www.isaric.org

[ProMED-mail is posting this announcement as part of our mission to disseminate information on emerging diseases and facilitate activities that would lead to the control of emerging diseases. Those institutions/individuals interested in collaborating in the above mentioned activity should contact Kajsa-Stina Magnusson, the ISARIC project manager at <kajsa-stina.magnusson@ndm.ox.ac.uk>. - Mod.MPP]

NOVEL CORONAVIRUS - EASTERN MEDITERRANEAN (04): RECEPTOR CHARACTERIZATION
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Date: Mon 10 Dec 2012
Source: Winnipeg Free Press, The Canadian Press report [edited]
http://www.winnipegfreepress.com/canada ... 25971.html


A new study reveals that the new SARS-like coronavirus, which has been causing infections in the Middle East, behaves unusually in laboratory testing. The unexpected behaviour of the virus may help to explain the pattern of spread of the cases so far, says senior author Christian Drosten, a leading coronavirus expert. [Reference and Abstract reproduced below. - Mod.CP]

In essence, the new coronavirus is promiscuous, a term the virologists who authored the study use to describe the fact that it will grow in a variety of different types of animal cells, including cells from people, pigs, and several species of bats. That is not true for other known coronaviruses, which typically only grow in cells from the species they infect, says Drosten, who is the director of the institute of virology at the University of Bonn Medical Center, in Bonn, Germany. Dutch virologist Ron Fouchier agrees that the finding is surprising. "This is certainly unusual for a (corona)virus to have such a broad cellular host range," says Fouchier, a senior scientist with Erasmus Medical Centre in Rotterdam.

The virus goes by the name hCoV-EMC, which is short for human coronavirus Erasmus Medical Centre [EMC]. Fouchier's lab was the first to sequence the full genetic code of the new virus. It is known to have infected at least 9 people from April [2012] onward, with cases recorded in Jordan, Saudi Arabia, and Qatar. 5 of the infected people have died. For this study, the researchers wanted to see if the new virus uses the same cell receptor as the virus that caused SARS. It was also a coronavirus.

Finding out what cells the new virus latches onto would help scientists assess the risk it poses. For instance, the SARS coronavirus attached to receptors found deep in human lungs. That meant in order to get sick, people had to have been exposed to a large dose of the virus, and have breathed it deep into their lungs. That probably explains why [the] SARS [coronavirus] made many of its victims so very ill; SARS killed roughly 11 per cent of the people it infected. But it also likely limited the SARS virus's ability to spread easily from person to person and may have helped in the eventual containment of the 2003 outbreak.

The EMC coronavirus does not use the same receptor that SARS does, the scientists found. At the time of the writing of the paper, published in the journal mBio [abstract below], they hadn't managed to find the receptor the EMC virus uses. But they did discover that it will grow in cells from 5 different species of bats, and in cells from pigs and humans. That is "absolutely unique among coronaviruses," they wrote. Drosten explains that when coronaviruses are found to have jumped into a new species, by the time science has detected the event the viruses have adapted to their new hosts. SARS is a good example. It is believed the SARS virus came from a similar coronavirus that infects bats. But if you try to infect bat cells with the SARS coronavirus, it won't work. Having switched species, the virus moved on, Drosten says. "The usual concept for the coronaviruses is that as soon as you see this virus in human, it's actually irrelevant where it came from because the problem is there. We have it in humans," he says.

Given that paradigm -- which holds true for other known coronaviruses -- experts like Drosten were worried when sporadic cases of human infections with the new virus came to light this fall. He feared the virus had left its animal reservoir and was spreading from person to person, with mild infections passing under the radar and only the severe cases coming to light.

But given that this virus seems to be able to infect multiple species -- at least in the lab -- that might suggest a pattern where the geographically and temporally distant cases are being infected from animal sources, not people, Drosten admits. In some respects, that's a more reassuring idea. But in others, it's not. If the virus is able to infect a number of types of animals, it could continue to make periodic jumps to humans -- which could impede containment efforts. If the EMC coronavirus were to get into animals farmed in the Middle East, for instance, human exposures could be ongoing, Fouchier says. "From looking at these data . . . you would think the zoonotic potential of a virus like this would be higher than something like the SARS coronavirus, which is more restricted," he says. A zoonosis is an animal disease that crosses the species barrier to infect people. The risk will depend in part on how well the virus transmits, which at this point is still a mystery. But Drosten says veterinary surveillance should be going on to look for the virus in livestock and wild animals in the Middle East.

[Byline: Helen Branswell]

--
Communicated by:
ProMED-mail Rapporteur Mary Marshall

[The following is the citation for the publication referred to in the preceding press article:

Mueller MA, et al. 2012: Human coronavirus EMC does not require the SARS-coronavirus receptor and maintains broad replicative capability in mammalian cell lines. mBio 3(6): e00515-12. doi:10.1128/mBio.00515-12; http://mbio.asm.org/content/3/6/e00515-12

"Abstract
---------
A new human coronavirus (hCoV-EMC) has emerged very recently in the Middle East. The clinical presentation resembled that of the severe acute respiratory syndrome (SARS) as encountered during the epidemic in 2002/2003. In both cases, acute renal failure was observed in humans. HCoV-EMC is a member of the same virus genus as SARS-CoV but constitutes a sister [!] species. Here we investigated whether it might utilize angiotensin-converting enzyme 2 (ACE2), the SARS-CoV receptor. Knowledge of the receptor is highly critical because the restriction of the SARS receptor to deep compartments of the human respiratory tract limited the spread of SARS. In baby hamster kidney (BHK) cells, lentiviral transduction of human ACE2 (hACE2) conferred permissiveness and replication for SARS-CoV but not for hCoV-EMC. Monkey and human kidney cells (LLC-MK2, Vero, and 769-P) and swine kidney cells were permissive for both viruses, but only SARS-CoV infection could be blocked by anti-hACE2 antibody and could be neutralized by preincubation of virus with soluble ACE2. Our data show that ACE2 is neither necessary nor sufficient for hCoV-EMC replication. Moreover, hCoV-EMC, but not SARS-CoV, replicated in cell lines from _Rousettus_, _Rhinolophus_, _Pipistrellus_, _Myotis_, and _Carollia_ bats, representing 4 major chiropteran families from both suborders. As human CoV normally cannot replicate in bat cells from different families, this suggests that hCoV-EMC might use a receptor molecule that is conserved in bats, pigs, and humans, implicating a low barrier against cross-host transmission.

Importance
----------
A new human coronavirus (hCoV) emerged recently in the Middle East. The disease resembled SARS (severe acute respiratory syndrome), causing a fatal epidemic in 2002/2003. Coronaviruses have a reservoir in bats and because this novel virus is related to SARS-CoV, we investigated whether it might replicate in bat cells and use the same receptor (angiotensin-converting enzyme 2 [ACE2]). This knowledge is highly critical, because the SARS-CoV receptor influenced pathology, and its localization in the deep respiratory tract is thought to have restricted the transmissibility of SARS. Our data show that hCoV-EMC does not need the SARS-CoV receptor to infect human cells. Moreover, the virus is capable of infecting human, pig, and bat cells. This is remarkable, as human CoVs normally cannot replicate in bat cells as a consequence of host adaptation. Our results implicate that the new virus might use a receptor that is conserved between bats, pigs and humans suggesting a low barrier against cross-host transmission."

In the case of many viruses the susceptibility of cultured cells to virus infection would not usually correspond to the in vivo host range of the virus. But Christian Drosten and his colleagues have produced persuasive evidence that this might be so in the case of the novel viruses, classified in the genus _Coronavirus_, that has appeared in the Eastern Mediterranean region - Mod.CP

As of now there are still more questions than answers on the epidemiology of this novel coronavirus. We await results of additional studies on human and animal contacts of confirmed cases to further define the epidemiology of this novel organism. - Mod.MPP]

NOVEL CORONAVIRUS - EASTERN MEDITERRANEAN (05): WHO, TRANSMISSION ROUTE, JORDAN
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Date: 21 Dec 2012
Source: GAR [edited]
http://www.who.int/csr/disease/coronavi ... index.html


Background and summary of novel coronavirus infection -- as of [21 Dec 2012]
-----------------------------------------------------
Over the past 3 months, WHO has received reports of 9 cases of human infection with a novel coronavirus. Coronaviruses are a large family of viruses; different members of this family cause illness in humans and animals. In humans, these illnesses range from the common cold to infection with severe acute respiratory syndrome (SARS) coronavirus (SARS CoV).

This summary provides the latest information on all reported cases and provides details of a WHO mission to Jordan, which has concluded since the last web update.

Thus far, the laboratory confirmed cases have been reported by Qatar (2 cases), Saudi Arabia (5 cases), and Jordan (2 cases). All patients were severely ill, and 5 have died.

A total of 5 confirmed cases have been reported from Saudi Arabia. The 1st 2 are not linked to each other and lived in different parts of the country; one of these has died. Three other confirmed cases are epidemiologically linked and occurred in one family living within the same household; 2 of these have died. One additional family member in this household also became ill, with symptoms similar to those of the confirmed cases. This person has recovered and tested negative, by polymerase chain reaction (PCR) tests, for the virus.

Two confirmed cases have been reported in Jordan. Both of these patients have died. These cases were discovered through testing of stored samples from a cluster of pneumonia cases in health care workers that occurred in April 2012.

In November 2012, staff from WHO Headquarters and the Eastern Mediterranean Regional Office were invited to Jordan to assess severe acute respiratory infection (SARI) surveillance and infection prevention and control measures, and to review the April 2012 outbreak. The mission included hospital site visits, interviews with patients, relatives and caregivers, and review of case files. In addition to the 2 previously confirmed cases, a number of health care workers with pneumonia associated with the cases were also included in the review and are now considered probable cases.

The main findings of this mission are:

- The index case among this cluster could not be determined.
- All patients had significant respiratory disease presenting as pneumonia. Disease was generally milder in the unconfirmed probable cases. One patient who is a probable case had symptoms that were mild enough to be managed at home and was not admitted to hospital.
- No patient in this cluster had renal failure.
- One patient presented with pneumonia and was discovered to also have pericarditis. This patient had laboratory confirmation of infection and has died.
- A 2nd patient developed disseminated intravascular coagulation as a complication of severe respiratory disease. This patient also had laboratory confirmation of infection and has died.
- The method of exposure is uncertain.
- There was no history of travel or contact with animals among confirmed or probable cases.
- Most family members and health care workers who were closely exposed to confirmed and probable cases did not develop respiratory disease. However, the appearance of pneumonia in some who provided care and in at least 2 family members with direct personal contact increases the suspicion that person-to-person transmission may have occurred. The possibility of exposure to a common source has not been definitively excluded. Further investigation with serological testing (when it becomes available) to confirm additional cases may help determine the types of exposures that result in infection.

The current understanding of this novel virus is that it can cause a severe, acute respiratory infection presenting as pneumonia. The additional unconfirmed probable cases in Jordan indicate that milder presentations may also be a part of the clinical appearance associated with infection. Acute renal failure has occurred in 5 of the 9 confirmed cases but was not a prominent feature of the Jordanian cluster. In addition, pericarditis and disseminated intravascular coagulation have now been seen in 2 confirmed cases.

WHO recognizes that the emergence of a new coronavirus capable of causing severe disease raises concerns because of experience with SARS. Although this novel coronavirus is distantly related to the SARS CoV, they are different. Based on current information, it does not appear to transmit easily or sustainably between people, unlike the SARS virus.

WHO has closely monitored the situation since detection of the 1st case and has been working with partners to ensure a high degree of preparedness should the new virus be found to be sufficiently transmissible to cause community outbreaks. Some viruses are able to cause limited human-to-human transmission under conditions of close contact, as occurs in families, but are not transmissible enough to cause larger community outbreaks.

Actions taken by WHO in coordination with national authorities and technical partners include the following:

- Investigations are ongoing to determine the likely source of infection and the route of exposure. Close contacts of confirmed cases are being identified and followed up.

- An interim surveillance recommendation has been updated to assist clinicians to determine which patients should undergo laboratory testing for the presence of novel coronavirus.

- Laboratory assays for the virus have been developed. Reagents and other materials for testing are available, as are protocols, algorithms, and reference laboratory services. WHO has activated its laboratory network to assist in testing and other services. WHO has now issued preliminary guidance for laboratory biorisk management.

The 3 affected countries either have already acquired or are in the process of acquiring the capacity to test for the novel coronavirus in national laboratories and have enhanced their surveillance activities according to WHO guidance along with other countries in the area.

WHO has created a webpage for coronavirus infections, with guidance for surveillance, infection control, biorisk management, and laboratory testing, which can be found at http://www.who.int/csr/disease/coronavi ... index.html.

Based on the current situation and available information:

- WHO encourages all member states to continue their surveillance for severe acute respiratory infections (SARI) and to carefully review any unusual patterns. Furthermore, testing for the new coronavirus of patients with unexplained pneumonias should be considered, especially in persons residing in or returning from the Arabian peninsula and neighboring countries. Any new cases should be promptly reported both to national health authorities and to WHO.

- When collecting specimens for testing, priority should be given to collection of lower respiratory tract specimens such as sputum and endotracheal aspirates (for intubated patients).

- In addition, any clusters of SARI or SARI in health care workers should be thoroughly investigated, regardless of where in the world they occur. These investigations will help determine whether the virus is distributed more widely in the human population beyond the 3 countries that have identified cases.

- Health care workers should be advised to scrupulously adhere to standard infection control precautions for all patients. Droplet precautions should be added to standard precautions for any patient known or suspected to have an acute respiratory infection, including patients with suspected or confirmed infection with novel coronavirus. Airborne precautions should be used for aerosol-generating procedures, including intubation and related interventions. Details can be found on the website listed above.

- WHO does not advise special screening at points of entry with regard to this event nor does it recommend that any travel or trade restrictions be applied.

WHO continues to monitor this situation closely. Unless information is received that changes our understanding of this virus and the disease it causes, the next web update is expected to be posted during the 2nd week of January 2013.

--
communicated by:
ProMED-mail
<promed@promedmail.org>

[The above report provides additional information on a retrospective investigation of the outbreak in Jordan during April 2012. As a reminder, this outbreak (Jordan) remained as an unknown etiology outbreak of severe acute respiratory illness (SARI) until after the novel coronavirus (nCoV) had been identified in the initial 2 reported cases: the report in September 2012 of the 1st identified case in a Saudi Arabian citizen (illness having occurred in June 2012), followed by the report of a 2nd case in a Qatari citizen hospitalized in the UK. Retrospective testing of saved specimens from the cluster of cases in Jordan confirmed the etiology of the outbreak to have been the nCoV involved in Saudi Arabia and Qatar.

While the above report does not mention the number of cases involved in the Jordanian cluster, a report from the European Centre for Disease Control (ECDC) on 3 May 2012 mentioned that there had been 11 cases including 2 deaths.

Points of interest include the absence of identification of the "index case" in the above outbreak. The outbreak involved individuals associated with an intensive care unit (ICU), and it seemed logical to suspect that the index case in this cluster was a patient admitted with a SARI who then infected individuals working in the ICU. Another point of interest is the discussion on the need for development of serologic tests that will permit a better look at the baseline prevalence of prior infections in the community, especially those cases of respiratory illness in contacts of confirmed cases that have tested negative for nCoV infection with the current PCR test available.

If one looks at the epidemic curve of the SARS outbreak, one sees there were one or 2 cases identified sporadically, separated by several weeks, beginning with the presumed index case with date of onset on 22 Nov 2002. It was not until mid to late December 2002 that there were apparent small clusters followed by apparent continual transmission occurring in January 2003. (see Probable cases of SARS by week of onset, Worldwide (5910) 1 Nov 2002 - 10 Jul 2003 http://www.who.int/csr/sars/epicurve/ep ... ndex1.html. One can't help but wonder on the one hand whether there had been other isolated cases occurring during the period prior to 22 Nov 2002 that were "missed" during the investigations. On the other hand, one wonders whether we might be seeing a similar beginning pattern with this nCoV: isolated/sporadic cases and small clusters with probable person-to-person transmission as a prelude to the virus transitioning into more efficient person-to-person transmission. One hopes that, with the experience of SARS in the not-too-distant past and the lessons learned from that experience, the use of respiratory precautions in the healthcare setting will prevent the development of efficient continued transmission of this nCoV.

For the HealthMap/ProMED map of the Eastern Mediterranean region where the 9 confirmed cases have occurred (Saudi Arabia, Qatar, Jordan), see http://healthmap.org/r/1HAJ. - Mod.MPP]

NOVEL CORONAVIRUS - EASTERN MEDITERRANEAN: BAT RESERVOIR
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Date: Mon 21 Jan 2013
Source: The Huffington Post [edited]
http://www.huffingtonpost.ca/2013/01/21 ... 18541.html


New coronavirus-like virus found in bats
----------------------------------------
Viruses closely related to the new coronavirus that emerged last year [2012] in the Middle East have been discovered in specimens from a number of species of bats found widely throughout Europe and beyond, a new study shows.

The work suggests bats common to Europe, Russia, parts of Asia and Africa, and the Middle East may carry viruses that are very closely related to the new coronavirus, called EMC 2012 [the virus has also been referred to as nCoV -- novel coronavirus].

The study will be published in the March [2013] issue of the journal Emerging Infectious Diseases.

The findings, while interesting, don't help to narrow down how a dozen or more people in 3 countries have been sickened by the new virus, or whether more have been infected but have escaped notice because their symptoms were mild.

The researchers said bats from the Arabian Peninsula should be tested to see if they carry similar viruses. But senior author Dr Christian Drosten cautioned that because of the wide geographic distribution of these bats, it cannot be concluded that the bat virus that evolved into the new coronavirus did so in the Middle East.

"It could have come up in any other region where those bats are prevalent," said Drosten, a coronavirus expert and director of the Institute of Virology at the University of Bonn Medical Centre in Germany.

While it is believed the new virus came from bats, it's not known whether it moved directly from bats to people -- through exposure to bat guano or urine, for instance -- or whether some other animal or animals such as some form of livestock became infected and passed the virus on.

The SARS coronavirus, a cousin of EMC 2012, evolved from a bat virus that made its way into wild animals -- civet cats and raccoon dogs -- that are eaten as delicacies in China. "We don't know (yet) what the raccoon dog is for this virus, but there may be one," Drosten said.

He and colleagues had done previous research on bats in Ghana and in 4 countries in Europe -- the Netherlands, Romania, Germany, and Ukraine. As a result of that earlier work, they had stored fecal samples from nearly 5000 bats. After EMC 2012 emerged, they tested the samples looking for coronaviruses.

They found previously unknown viruses related to the new coronavirus in nearly 25 per cent of _Nycteris_ bats, and 15 per cent of _Pipistrellus_ bats. The viruses from the latter were most closely related to EMC 2012. In one case, the genetic codes differed by less than 2 per cent.

Three of 4 _Pipistrellus_ bat species tested positive for the similar coronaviruses, Drosten said. "The whole Old World region is full of different _Pipistrellus_ species. And I wouldn't be surprised if all of them contain related viruses."

So if these bats commonly carry viruses similar to the new coronavirus and carry them throughout many parts of the world, why have infections only been seen in Saudi Arabia, Qatar, and Jordan? And why now?

Do the cases -- 9 confirmed plus a similar number of probable cases -- represent multiple introductions of virus from bats to people, like sparks from a fire? Or did the virus jump once and spread, mostly unseen, from person to person?

At present, those questions have no answers. But there are ways to find clues, particularly to the question of whether the virus made multiple jumps from its bat reservoir.

Generating genetic sequences from all the viruses that have infected humans -- where virus has been isolated or virus fragments are available -- would give scientists information to compare.

Each type of virus evolves at a particular rate. The speed is referred to as its molecular clock. Comparing genetic sequences from the 1st known cases to later cases should show if the human viruses have evolved from one another.

The 1st spotted case was a man from Jeddah, Saudi Arabia who died in June [2012]. But in November [2012], a Cairo-based US naval research laboratory confirmed that 2 people who died in Jordan in April 2012 had been infected with the new virus.

"We will never have a definite answer unless we find the source. But we will have very, very clear hints if we sequence more viruses," Drosten said. "The further apart in time, and in geography, those virus sequences are, the more we will learn."

[Byline: Helen Branswell]

--
Communicated by:
ProMED-mail from HealthMap alerts
<promed@promedmail.org>

[According to Shalmon's field guide to the land mammals of Israel, the following 5 _Pipistrellus_ bats have been identified in Israel: _P. ariel_, _P. kuhlii_, _P. pipistrellus_, _P. rueppellii_ and _P. savii_.

In Jordan, the following 6 _Pipistrellus_ bats have been recorded: _P. ariel_, _P. kuhlii_, _P. nathusii_, _P. pipistrellus_, _P. pygmaeus_, and _P. rueppellii_ - Mod.AS]

[The article referred to, Annan A, Baldwin HJ, Corman VM, Klose SM, Owusu M, Nkrumah EE et al: Human betacoronavirus 2c EMC/2012-related viruses in bats, Ghana and Europe. Emerg Infect Dis [Internet]. 2013 Mar [accessed 21 Jan 2013], can be found at http://wwwnc.cdc.gov/eid/article/19/3/1 ... rticle.htm.

Abstract
--------
"We screened fecal specimens of 4758 bats from Ghana and 272 bats from 4 European countries for betacoronaviruses. Viruses related to the novel human betacoronavirus EMC/2012 were detected in 46 (24.9 percent) of 185 _Nycteris_ bats and 40 (14.7 percent) of 272 _Pipistrellus_ bats. Their genetic relatedness indicated EMC/2012 originated from bats."

The authors mention that "Within the Arabian Peninsula, the International Union for Conservation of Nature (http://www.iucn.org) lists 50 bat species, including _P. arabicus_, _P. ariel_, _P. kuhlii_, _P. pipistrellus_, _P. rueppellii_, and _P. savii_ bats."

The identification of betacoronaviruses related to the nCoV associated with severe acute respiratory infections affecting individuals in Saudi Arabia, Jordan, and Qatar last year (2012) in several bat species in Ghana and Europe that include bat species found in the Eastern Mediterranean region is not surprising and further supports a hypothesis that the human infections were a result of species jump from bat to humans. What is not known as yet, is whether this species' jump was directly from human contact with infected bat secretions or if there is/was an intermediate host such as livestock in the region that may have been infected through contact with bat secretions, and humans were then infected through contact with the infected animals in the region as mentioned in the above newswire. Results of studies on the animal populations in the region are eagerly awaited. - Mod.MPP]

[A relevant reference on the role of bats as a reservoir for emerging viruses is Calisher CH, Childs JE, Field HE, et al: Bats: important reservoir hosts of emerging viruses. Clin Microbiol Rev. 2006 Jul; 19(3): 531-45 (full article available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1539106/, references available at source URL).

"Bats evolved early and have changed relatively little in comparison with mammals of other taxa (69). Although the fossil record of bat evolution is incomplete, a recent analysis of 17 nuclear genes dated the origin of chiropterans to the Eocene period (52 to 50 million years ago), coincident with a significant rise in global temperature. 3 major microchiropteran lineages were traced to Laurasia and a 4th to Gondwana. The correspondingly ancient origins deduced for certain zoonotic viruses maintained in bats, such as the henipaviruses and lyssaviruses, suggest a long history of cospeciation. Viruses that evolved with bats may have used for replication cellular receptors and biochemical pathways, which are conserved in mammals that evolved later and which underwent radiation in later geological periods. If so, these conserved cellular receptors and pathways could enhance the capacity for transmission of bat-associated viruses to other mammals.

"In 2002, a previously unrecognized coronavirus (family _Coronaviridae_) was found to cause a new, severe acute respiratory syndrome in humans [92, 125). This virus, named SARS-CoV, is a distant relative of the group 2 coronaviruses that infect rodents, cattle, dogs, pigs, and humans and has been assigned to group 2b (58). It is distinct from 2 other coronaviruses recently identified in bats in southern China (84, 119).

"Epidemiologic studies showed that the earliest cases of SARS were associated with the wildlife meat industry. A survey of wildlife in a Shenzhen market recovered SARS-CoV-like viruses from masked palm civets (_Paguma larvata_) and raccoon dogs (_Nyctereutes procyonoides_) and detected antibodies to the SARS-CoV-like virus in a hog badger (_Arctonyx collaris_)(63). Interestingly, the epidemiology of the outbreak in animals in the wildlife meat market resembled that of shipping fever, a viral syndrome that occurs when animals from different farms are comingled under crowded, stressful conditions. Under such circumstances, immune responses to persistent virus infections are reduced, virus shedding is increased, and susceptible animals become infected and shed virus. In the marketplace where SARS-CoVs were detected, viral RNA from some animals that were seronegative was detected by reverse transcription-PCR, suggesting acute infection, while other animals had antibodies to SARS-CoV but continued to shed virus, suggesting persistent infections (63). Although no pathology was associated with SARS-CoV in animals in this market, civets inoculated with human isolates of SARS-CoV had severe lung pathology (156). By sequencing many viral genomes from SARS patients, wild and farmed civets, and other animals, a dendrogram was generated that showed that the 1st human SARS coronaviruses were closely related to a contemporary virus from masked palm civets and that point mutations were selected and accumulated later, as the virus passed from human to human (139).

"Extensive surveys of viruses in domestic animals, poultry, and wildlife were done by reverse transcription-PCR to identify the natural reservoir of SARS-CoV. Palm civets were found to be an incidental host rather than the principal host for SARS-CoV. Recently, several groups simultaneously identified bats from different locations in southern China as being infected with SARS-CoV-like viruses or having antibody to these newly recognized coronaviruses, including members of several species of Chinese horseshoe bats (suborder _Microchiroptera_, family _Rhinolophidae_, genus _Rhinolophus_) (Tables 1 and 2) (42, 84, 86). The prevalence of antibody to bat SARS-CoV in some species of Chinese horseshoe bats was as high as 84 percent. Pathology has not yet been associated with SARS-CoV infection of bats.

"The genomes of SARS-CoV isolates recovered from civets and humans during the 2002-to-2003 outbreak of SARS lay phylogenetically within the broad group of SARS-CoV-like viruses of bats (86). These data show that the virus responsible for the 2002-to-2003 outbreak most likely originated from this group of bat-associated viruses. Antibody against SARS-CoV-like viruses of bats was also detected in Leschenault's rousette (_Rousettus leschenaultia_), a cave-dwelling megachiropteran, suggesting that fruit bats also may support infection with SARS-CoV-like viruses. Thus, the natural history of SARS-CoV appears to involve a previously unrecognized SARS-CoV-like virus of bats being transmitted in meat markets to amplifying hosts, including masked palm civets, raccoon dogs, and a hog badger, and then spilling over to infect humans in close contact with these intermediate hosts or their tissues. Subsequent human-to-human transmission of the virus was associated with adaptive mutations in the viral genome (139)." - Mod.CP]

WHO warnt vor SARS-ähnlichem Virus

Zehn Jahre ist es her, dass SARS die Welt in Schrecken versetzte. Nun scheint sich ein neues, SARS-ähnliches Coronavirus auszubreiten. Bei zwölf Patienten wurde es bereits nachgewiesen, fünf von ihnen sind daran gestorben. Das Prekäre: Es könnte sein, dass das neue Virus von Mensch zu Mensch übertragbar ist. mehr...

Infizierte und Todesfälle gab es bisher in Pakistan, Saudiarabien und Jordanien.

Grüsse
Alexander

Novel coronavirus infection – update
11.02.2013 - WHO

11 February 2013 - The United Kingdom (UK) has informed WHO of a confirmed case with infection of the novel coronavirus (NCoV). The case is a UK resident who developed symptoms of illness on 26 January 2013. Laboratory investigations on respiratory specimens have revealed both an Influenza A(H1N1)pdm09 infection and a confirmed NCoV infection. He is hospitalized in intensive care unit.

Preliminary investigation reveals that the patient had a history of travel to Pakistan and Saudi Arabia. Further investigation into the case is ongoing.

The Health Protection Agency (HPA) has instituted stringent infection control measures around the patient and identified contacts who may have been exposed to the patient during his illness.

This is a sporadic case and does not alter the current WHO risk assessment on NCoV but the new case does indicate that the virus is persistent. As of 11 February 2013, a total of 10 confirmed cases of human infection with a novel coronavirus have been notified to WHO.

Based on the current situation and available information, WHO encourages all Member States to continue their surveillance for severe acute respiratory infections (SARI) and to carefully review any unusual patterns. Testing for the new coronavirus of patients with unexplained pneumonias, or patients with severe, progressive or complicated illness not responding to treatment, should be considered especially in persons residing in or returning from the Arabian peninsula and neighboring countries.

Any clusters of SARI or SARI in health care workers should be thoroughly investigated, regardless of where in the world they occur.

New human cases and clusters should be promptly reported both to national health authorities and to WHO.

WHO does not advise special screening at points of entry with regard to this event nor does it recommend that any travel or trade restrictions are applied.

Gruß
Birgitt

NOVEL CORONAVIRUS - EASTERN MEDITERRANEAN (02): UK ex SAUDI ARABIA, PAKISTAN, HUMAN CASE
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ProMED-mail is a program of the
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*****

HPA press release

Date: 11 Feb 2013
Source: HPA Press Release
http://www.hpa.org.uk/NewsCentre/Nation ... uspatient/


Case of novel coronavirus identified in the UK -- [11 Feb 2013]
----------------
The Health Protection Agency (HPA) can confirm the diagnosis of a further case of novel coronavirus infection in a UK resident, who had recently travelled to the Middle East and Pakistan. The patient is receiving intensive care treatment in a Manchester hospital. This latest case brings the total number of confirmed cases globally to 10, of which 2 have been diagnosed in the UK.

Professor John Watson, head of the respiratory diseases department at the HPA, said: "The HPA is providing advice to healthcare workers to ensure the patient under investigation is being treated appropriately and that healthcare staff who are looking after the patient are protected. Contacts of the case are also being followed up to check on their health.

"Our assessment is that the risk associated with novel coronavirus to the general UK population remains extremely low and the risk to travellers to the Arabian Peninsula and surrounding countries remains very low. No travel restrictions are in place but people who develop severe respiratory symptoms, such as shortness of breath, within ten days of returning from these countries should seek medical advice and mention which countries they have visited.

"Since the 1st case of novel coronavirus was diagnosed in the UK in September 2012, the HPA has maintained increased vigilance for illness caused by this virus, working closely with national and international authorities including the WHO and the European Centre for Disease Prevention and Control (ECDC). We have also produced updated guidance for health professionals in the UK on the investigation and management of possible cases."

Professor Maria Zambon, director of reference microbiology services at the HPA, said: "A battery of laboratory tests have been developed by the HPA to test for coronavirus infection when cases of severe respiratory illness are identified, which are not explained by other infectious causes. These tests, which detect the presence of virus in the body, are available for use by selected frontline HPA laboratories.

"In mid-November [2012] the HPA published the full genome sequence from the 1st UK patient, enabling scientists around the world to understand more about the diversity of this virus. This will help with efforts to determine the origin of the virus and develop strategies for treatment and prevention."

Coronaviruses are causes of the common cold but can also include more severe illness, such as SARS (Severe Acute Respiratory Syndrome). This new coronavirus was 1st identified in September 2012 in a patient who died from a severe respiratory infection in June 2012. The virus has so far only been identified in a small number of cases of acute, serious respiratory illness who presented with fever, cough, shortness of breath, and breathing difficulties.

Notes to editors:

1. Laboratory confirmed cases to date: 10

Saudi Arabia: 5 (3 deaths)
Jordan: 2 (2 deaths)
UK: 2 (1 patient from Qatar - receiving treatment, 1 patient from UK - receiving treatment)
Germany: 1 (patient from Qatar - discharged)


--
Communicated by:
ProMED-mail Rapporteur Mary Marshall

NOVEL CORONAVIRUS - EASTERN MEDITERRANEAN (03): SAUDI COMMENT
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Date: Tue 12 Feb 2013
From: Ziad A Memish <zmemish@yahoo.com> [edited]


The most recent WHO report of severe respiratory illness in a 60 year old British national warrants comment about limitations of the current novel coronavirus case definition [e.g., see ProMED post: Novel coronavirus - Eastern Med. (02): UK ex Saudi Arabia, Pakistan 20130212.1539086. - Mod.CP] Press releases following the UK Health Protection Agency's announcement again emphasize the fact that this individual has had contact with the Middle East though the incubation period and appearance of symptoms are ambiguous enough that a more cautious statement is needed, that is, that it remains unknown where and when this patient became infected. As well, a finding of dual novel coronavirus and 2009 H1N1 [influenza A(H1N1)pdm09] influenza genes by molecular test methods should be interpreted with caution until confirmation is available from an independent source. We have made a thorough search for dual infections (both viral and bacterial) on our SARI [severe acute respiratory infection] cases, and have yet to find any. Meanwhile the incidence and severity of influenza infections have made headlines this winter [e.g., see the ProMED post: Influenza (17): Czech Republic, severity 20130208.1535245, - Mod.CP] Alerts for severe 2009 H1N1 infections are prominent on south Asian websites following reports of flu deaths in India last week [e.g., see ProMED-mail post Influenza (15): India (RJ) mortality 20130204.1528727. - Mod.CP] To put the matter in context, morbidity and mortality from influenza this winter will dwarf the 9 [now 10] cases of novel coronavirus infections reported so far.

Saudi Arabia continues to conduct surveillance for novel coronavirus in patients who meet the current SARI definition. It is one of several agents being investigated at our laboratories and by our colleagues at outside referral labs. During the last Hajj season [2012], we were able to test more than 300 sick pilgrims and found no evidence of novel coronavirus infection. Neither was this virus detected by our French (1) and Egyptian colleagues (personal communication) who reported surveillance findings on returned pilgrims. Our efforts to identify cases are ongoing, but now that validated detection tests are commercially available (2), we recommend that an expanded search for this virus is undertaken. Thus far it is less associated with focused or even regional outbreaks than it is with sporadic disease in widely separated locales. Unless and until SARI investigations are expanded, our understanding of its epidemiology and disease spectrum will remain limited. An urgent discussion of the current case definition is needed.

References
----------
1. Gautret P, Charrel R, Belhouchat K, et al: Lack of nasal carriage (hCoV) in French Hajj pilgrims returning from the Hajj 2012, despite high rate of respiratory symptoms. DOI: 10.1111/1469-0691.12.166. 11 Feb 2013 [abstract available at http://onlinelibrary.wiley.com/doi/10.1 ... 4/abstract].

2. Corman VM, Muller MA, Drosten C, et al: Assays for laboratory confirmation of novel human coronavirus infections. Euro Surveill. 2012; 17(49): pii=20334; available at http://www.eurosurveillance.org/ViewArt ... leid=20334.

--
Ziad A Memish, MD,FRCPC,FRCPE,FRCPL,FACP
Deputy Minister for Public Health
Ministry of Health
Professor, College of Medicine
AlFaisal University
Riyadh
Kingdom of Saudi Arabia
<zmemish@yahoo.com>

[ProMED-mail in general supports Dr Memish's reservation that the existing data regarding the epidemic potential of the recently characterised novel coronavirus are sparse and should not be over-interpreted. The increasing availability of accurate diagnostic reagents and methodologies should help achieve a better understanding of the epidemiology of the disease. It is unfortunate that results of field studies aimed at identifying possible transmission exposure risks are not available as yet to try to address epidemiologic issues in a scientific manner. - Mod.CP

A HealthMap/ProMED-mail map can be accessed at: http://healthmap.org/r/1HAJ.]

Novel coronavirus infection – update
13.02.2013 - WHO

The United Kingdom (UK) has informed WHO of another confirmed case of infection with the novel coronavirus (NCoV). The patient is a UK resident and a relative of the case announced on 11 February 2013.

The latest confirmed case does not have any recent travel history outside the UK and is currently hospitalized in an intensive care unit. It is understood that this patient has pre-existing medical conditions that may have increased susceptibility to respiratory infections.

Confirmed NCoV in a person without recent travel history indicates that infection was acquired in the UK. To date, evidence of person-to-person transmission has been limited. Although this case is suggestive of person-to-person transmission, on the basis of current evidence, the risk of sustained person-to-person transmission appears to be very low.

The Health Protection Agency (HPA) is following up on all close contacts (family and healthcare workers) who may have been exposed to either of these two new confirmed cases.

As of 13 February 2013, a total of 11 confirmed cases of human infection with NCoV have been notified to WHO, with no change in the number of fatalities i.e., five deaths since April 2012.

Based on the current situation and available information, WHO encourages all Member States to continue their surveillance for severe acute respiratory infections (SARI) and to carefully review any unusual patterns. Testing for the new coronavirus should be considered in patients with unexplained pneumonias, or in patients with unexplained severe, progressive or complicated respiratory illness not responding to treatment.

Any clusters of SARI or SARI in healthcare workers should be thoroughly investigated, regardless of where in the world they occur.

New cases and clusters of the NCoV should be reported promptly both to national health authorities and to WHO.

WHO does not advise special screening at points of entry with regard to this event nor does it recommend that any travel or trade restrictions be applied.

WHO continues to monitor closely the situation.

Gruß
Birgitt

NOVEL CORONAVIRUS - EASTERN MEDITERRANEAN (04): UK, PERSON TO PERSON TRANSMISSION SUSPECTED
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ProMED-mail is a program of the
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http://www.isid.org


In this report:

[1] HPA press release
[2] ECDC


******

[1] HPA press release

Date: 13 Feb 2013
Source: HPA UK Press Release [edited]
http://www.hpa.org.uk/NewsCentre/Nation ... uspatient/


The Health Protection Agency (HPA) can confirm a further case of novel coronavirus infection in a family member of the case announced on Monday [11 Feb 2013]. The patient, who is a UK resident, does not have any recent travel history and is currently receiving intensive care treatment at The Queen Elizabeth Hospital, Birmingham. It is understood that this patient has an existing medical condition that may make them more susceptible to respiratory infections. This latest case brings the total number of confirmed cases globally to 11, of which 3 have been diagnosed in the UK.

Professor John Watson, head of the respiratory diseases department at the HPA, said: "Confirmed novel coronavirus infection in a person without travel history to the Middle East suggests that person-to-person transmission has occurred and that it occurred in the UK. This case is a family member who was in close personal contact with the earlier case and who may have been at greater risk of acquiring an infection because of their underlying health condition. To date, evidence of person-to-person transmission has been limited. Although this case provides strong evidence for person to person transmission, the risk of infection in most circumstances is still considered to be very low. If novel coronavirus were more infectious, we would have expected to have seen a larger number of cases than we have seen since the 1st case was reported 3 months ago. However, this new development does justify the measures that were immediately put into place to prevent any further spread of infection and to identify and follow up contacts of known cases. We will continue to provide advice and support to healthcare workers looking after the patients and to contacts of both cases. In light of this latest case, we would like to emphasise that the risk associated with novel coronavirus to the general UK population remains very low. The HPA will continue to work closely with national and international health authorities and will share any further advice with health professionals and the public if and when more information becomes available."

Notes to editors:

Laboratory confirmed cases to date: 11
Saudi Arabia: 5 (3 deaths)
Jordan: 2 (2 deaths)
UK: 3 (1 patient from Qatar - receiving treatment, 2 patients from UK, 1 with recent travel to Pakistan and Saudi Arabia - both receiving treatment)
Germany: 1 (patient from Qatar - discharged)

Coronaviruses are causes of the common cold but can also include more severe illness, such as SARS (severe acute respiratory syndrome). This new coronavirus was 1st identified in September 2012 in a patient who died from a severe respiratory infection in June 2012. The virus has so far only been identified in a small number of cases of acute, serious respiratory illness who presented with fever, cough, shortness of breath, and breathing difficulties.

For further information, see the HPA's coronavirus web pages, which include a Q&A page on this topic [see http://www.hpa.org.uk/webw/HPAweb&Page& ... 7136202637].

--
Communicated by:
ProMED-mail
<promed@promedmail.org>

******
[2] ECDC Update
Date: 13 Feb 2013
Source: ECDC (European Centre for Disease Control) [edited]
http://ecdc.europa.eu/en/press/news/Lis ... sts%2FNews


Epidemiological update: Case of severe lower respiratory tract disease associated with a novel coronavirus:

On [13 Feb 2013], the HPA announced that one family contact of the previously-confirmed case reported on [11 Feb 2013] was laboratory-confirmed to be infected with the novel coronavirus (NCoV). This 2nd case from the same family was hospitalised on [9 Feb 2013] with a short history of respiratory symptoms. The patient has an existing medical condition that may make him more susceptible to respiratory infections. He does not have a recent travel history and is currently receiving intensive care treatment.

The cases have been notified through the EU alerting system for communicable diseases.

This brings the total of laboratory-confirmed cases of severe pneumonia caused by the NCoV to 11 globally (see table below).

The information available suggests human-to-human transmission of the NCoV in this family cluster.

The HPA reports that surveillance of family, close contacts of the 2 patients, and healthcare workers treating the 2 patients is ongoing, as per the UK National Guidelines. None are currently presenting with symptoms consistent with NCoV.

The HPA is also following-up regarding passengers who may have been exposed while flying with the case announced on [11 Feb 2013] and are in contact with the airline concerned.

In light of this human-to-human transmission of the NCoV within the family cluster, ECDC is now updating its risk assessment, previously published on [7 Dec 2012].

Case No: Date Onset / Age (years) / Sex / Probable place of infection / Date reported / Source / Outcome

1: April 2012 / 45/ F / Jordan** / 30 Nov 2012 / WHO/IHR / Dead

2: April 2012 / 25 / M / Jordan** / 30 Nov 2012 / WHO/IHR / Dead

3: 13 Jun 2012 / 60 / M / Kingdom of Saudi Arabia* / 20 Sep 2012 / Kingdom of Saudi Arabia, ProMED / Dead

4: 3 Sep 2012 / 49 / M / Qatar / Kingdom of Saudi Arabia*** / 22 Sep 2012 / HPA/WHO / Alive

5: NK / NK / NK / Kingdom of Saudi Arabia* / 4 Nov 2012 / Kingdom of Saudi Arabia, ProMED, SMJ / Alive

6: 12 Oct 2012 / 45 / M / Qatar**** / 23 Nov 2012 / RKI/WHO / Alive

7: NK / NK / M / Kingdom of Saudi Arabia* / 19-23 Nov 2012 / Kingdom of Saudi Arabia, ProMED, WHO / Alive

8: 28 Oct 2012 / NK / M / Kingdom of Saudi Arabia* / 23 Nov 2012 / WHO / Dead

9: October 2012 / NK / M / Kingdom of Saudi Arabia* / 28 Nov 2012 / WHO / Dead

10: 24 Jan 2013 / 60 / M / Pakistan, Kingdom of Saudi Arabia*/ 8 Jan 2013 / EWRS / Alive, Hospitalised

11: 6 Feb 2013 / NK / M / United Kingdom* / 12 Feb 2013 / HPA / Alive, Hospitalised

* Part of family cluster
** Healthcare worker and part of outbreak linked to hospital
*** Patient transferred to UK
**** Patient transferred to Germany
NK: not known

--
Communicated by:
ProMED-mail
<promed@promedmail.org>

NOVEL CORONAVIRUS- EASTERN MEDITERRANEAN (05): UK, 3RD CASE
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Date: 15 Feb 2013
Source: HPA Press Release [edited]
http://www.hpa.org.uk/NewsCentre/Nation ... ronavirus/


Third case of novel coronavirus infection identified in family cluster
[15 Feb 2013]
------------------
The Health Protection Agency (HPA) can confirm a 3rd case of novel coronavirus infection in a family cluster, following the confirmed diagnosis of 2 cases announced earlier this week. The patient, who is a UK resident and does not have any recent travel history, is recovering from a mild respiratory illness and is currently well. This latest case brings the total number of confirmed cases globally to 12, of which 4 have been diagnosed in the UK.

Professor John Watson, head of the respiratory diseases department at the HPA, said: "Although this patient had a mild form of respiratory illness, as a precaution the HPA is advising that the patient self-isolate and limit contact with non-household members. Follow up of other household members and contacts of this case is currently underway.

"Although this case appears to be due to person-to-person transmission, the risk of infection in contacts in most circumstances is still considered to be low. If novel coronavirus were more infectious, we would have expected to have seen a larger number of cases than we have seen since the 1st case was reported 3 months ago. However, this new development does justify the measures that were immediately put into place to prevent any further spread of infection and to identify and follow up contacts of known cases.

"We would like to emphasise that the risk associated with novel coronavirus to the general UK population remains very low. The HPA will continue to work closely with national and international health authorities and will share any further advice with health professionals and the public if and when more information becomes available."

ENDS

Notes to editors:

1. Laboratory confirmed cases to date: 12

Saudi Arabia: 5 (3 deaths)
Jordan: 2 (2 deaths)
UK: 4 (1 patient from Qatar - receiving treatment, 3 patients from UK, 2 receiving treatment, 1 recovered)
Germany: 1 (patient from Qatar - discharged)
2. Coronaviruses are causes of the common cold but can also include more severe illness, such as SARS (Severe Acute Respiratory Syndrome). This new coronavirus was first identified in September 2012 in a patient who died from a severe respiratory infection in June 2012. The virus has so far only been identified in a small number of cases of acute, serious respiratory illness who presented with fever, cough, shortness of breath, and breathing difficulties.

3. For further information, see the HPA's coronavirus webpages [http://www.hpa.org.uk/Topics/Infectious ... virus2012/] which includes a Q&A [http://www.hpa.org.uk/Topics/Infectious ... virus2012/] on this topic.

--
Communicated by:
ProMED-mail
<promed@promedmail.org>

[This case represents the 12th confirmed case of respiratory illness associated with infection with the novel coronavirus (nCoV) and the 3rd case in a family cluster in the UK (see prior ProMED-mail posts listed below). There have been 2 prior clusters of respiratory illness associated with the nCoV - one cluster with 2 fatalities confirmed involving ICU (Intensive care unit) staff in a hospital in Jordan in May 2012 and the 2nd family cluster in Saudi Arabia in November 2012. In the latter case, information was not available to determine if the cluster was due to common exposures or person-to-person transmission. In this cluster in the UK, the dates of onset of the cases are sequential and only the 1st case had the known risk factor of travel to Saudi Arabia where earlier cases have been identified. Hence it is fairly certain that there has been thus far limited person-to-person transmission.

For the interactive map ofFor the interactive HealthMap/ProMED map of the UK, see http://healthmap.org/r/1lNY. For the interactive HealthMap/ProMED map of the Middle East, see http://healthmap.org/r/1HAJ. - Mod.MPP]

A HealthMap/ProMED-mail map can be accessed at: http://healthmap.org/r/1lNY.]

Novel coronavirus infection – update
16.02.2013 - WHO

The United Kingdom (UK) has informed WHO of another confirmed case of infection with the novel coronavirus (NCoV). This is the third case confirmed in the country this month and is in the same family cluster as the two recently confirmed cases.

The latest confirmed case does not have recent travel history outside the UK. The case is recovering from mild respiratory illness and is currently well.

The confirmation with NCoV in this case with no recent travel history indicates that infection was acquired in the UK. Although this new case offers further indications of person-to-person transmission, no sustained person-to-person transmission has been identified.

The Health Protection Agency (HPA) is following up on all close contacts who may have been exposed to the recently confirmed cases.

As of 16 February 2013, WHO has been informed of a total of 12 confirmed cases of human infection with NCoV, including five deaths.

Based on the current situation and available information, WHO encourages all Member States to continue their surveillance for severe acute respiratory infections (SARI) and to carefully review any unusual patterns. Testing for the new coronavirus should be considered in patients with unexplained pneumonias, or in patients with unexplained severe, progressive or complicated respiratory illness not responding to treatment.

Any clusters of SARI or SARI in healthcare workers should be thoroughly investigated, regardless of where in the world they occur.

New cases and clusters of the NCoV should be reported promptly both to national health authorities and to WHO.

WHO does not advise special screening at points of entry with regard to this event nor does it recommend that any travel or trade restrictions be applied.

WHO continues to closely monitor the situation.

Gruß
Birgitt