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Published Date: 2012-10-04 20:56:50
Subject: PRO/AH/EDR> Novel coronavirus - Saudi Arabia (11): clin. lab. & epi. investigations
Archive Number: 20121004.1324712

NOVEL CORONAVIRUS - SAUDI ARABIA (11): CLINICAL, LABORATORY AND EPIDEMIOLOGICAL INVESTIGATIONS
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In this update:
[1] UK - HPA investigation findings, Eurosurveillance
[2] UK - Clinical and laboratory findings, Eurosurveillance
[3] Saudi Arabia - ongoing investigations, newswire
[4] USA - current recommendations, MMWR

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[1] UK - HPA investigation findings, Eurosurveillance
Date: 4 Oct 2012
Source: Eurosurveillance Volume 17, Issue 40, 4 Oct 2012 [edited]
http://eurosurveillance.org/ViewArticle.aspx?ArticleId=20292

Rapid communications
The United Kingdom Public Health response to an imported laboratory confirmed case of a novel coronavirus in September 2012
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On [22 Sep 2012], a novel coronavirus, very closely related to that from a fatal case in Saudi Arabia 3 months previously, was detected in a previously well adult transferred to intensive care in London from Qatar with severe respiratory illness. Strict respiratory isolation was instituted. Ten days after last exposure, none of 64 close contacts had developed severe disease, with 13 of 64 reporting mild respiratory symptoms. The novel coronavirus was not detected in 10 of 10 symptomatic contacts tested.

The outbreak of severe acute respiratory syndrome (SARS) in 2003, which led to 8422 cases and 916 deaths worldwide [1], highlighted the potential for newly emerging zoonotic coronaviruses to transmit from person to person, especially in healthcare settings, and to cause severe human illness.

On [22 Sep 2012], the Health Protection Agency (HPA) in London, United Kingdom (UK), confirmed infection with a novel coronavirus in a patient in a London hospital who had been transferred from Qatar 11 days previously. This patient represents the 2nd confirmed case of severe acute respiratory illness caused by this novel coronavirus. The 1st case was identified in a Saudi Arabian national who died in June 2012 [2,3]. We describe the exposure history, the public health response and follow-up of close contacts of the case in London.

Case exposure history and laboratory investigations
The case is a previously well 49-year-old male who travelled to Saudi Arabia from [31 Jul 2012 to 18 Aug 2012], where he and several of his travelling companions developed rhinorrhoea and fever (Figure 1). On [18 Aug 2012], he travelled to Qatar, where his respiratory symptoms resolved 3 days later. While in Qatar, he spent time on a farm, where he keeps camels and sheep, although no direct contact with these animals was reported.

On [3 Sep 2012], he reported a mild respiratory illness. Six days later, he required hospitalisation due to development of bilateral pneumonia. His condition worsened, and he subsequently required intubation and ventilation. On [12 Sep 2012], he was transferred by air ambulance to an intensive care unit in London, where acute renal impairment was also detected. Due to further deterioration, he was transferred to another London hospital on [20 Sep 2012] [3].

Following the report on ProMED-mail on [20 Sep 2012] [2] of the detection of a novel coronavirus (until further taxonomic denomination, herewith referred to as hCoV-EMC) in a Saudi Arabian patient who had died from severe respiratory illness and renal failure, and as no diagnosis had been established despite investigations for common causes of pneumonia and pathogens endemic to the Middle East, the patient in London was investigated for novel coronavirus infection. On [21 Sep 2012], a coronavirus was detected in respiratory tract samples using a pan-coronavirus PCR assay, and on [22 Sep 2012] sequencing of the PCR amplicon showed a sequence very closely related to the hCoV-EMC detected in the earlier patient from Saudi Arabia [4]. The virus belongs to the genus beta-coronavirus, with closest relationship to bat coronaviruses [4].

Figure 1. Timeline of disease and travel history of novel coronavirus case, London, August to September 2012 [available at above URL link]

Public health management
The identification of a novel coronavirus of the same group as the SARS-CoV, with 2 clinically severe human cases including one fatality, led to a public health response being mounted to isolate the case, identify and test close contacts and to prevent onward transmission. Once the patient was found to have a novel coronavirus infection, he was isolated in a negative-pressure single room, and full personal protective equipment (PPE), including gowns, gloves, eye protection and high filtration masks were worn by staff and other contacts. Interim case and close contact definitions were developed [5].

A possible case was defined as: any person with acute respiratory syndrome which includes fever (greater than or equal to 38 C), or history of fever and cough requiring hospitalisation, or with suspicion of lower airway involvement (clinical or radiological evidence of consolidation) not explained by another infection or aetiology with history of either travel to or residence in Saudi Arabia or Qatar, or close contact with a confirmed case in the 10 days before onset of illness.

A close contact was defined as the following:
- Healthcare and social care workers: workers who provided direct clinical or personal care or examination of a symptomatic confirmed case or within close vicinity of an aerosol generating procedure AND who was not wearing full personal protective equipment (PPE) at the time. Full PPE is defined as a correctly fitted high filtration mask (FFP3), gown, gloves and eye protection.
- Household: any person who had prolonged face-to-face contact with the confirmed case(s) any time during the illness after onset in a household setting.
- Other close contacts: any person who had prolonged face-to-face contact with a confirmed case while symptomatic in any other enclosed setting and who was not wearing a mask, e.g. school, visitor to the hospital to the bed side of a symptomatic confirmed case.

These definitions were used as the basis for identifying further possible cases and contacts. Guidelines were developed on the investigation and public health management of these cases and their close contacts.

Identification and follow-up of individuals who had close contact with the case at any time during his symptomatic period from entry into the UK up until implementation of full isolation on [21 Sep 2012] (including healthcare workers and family), was rapidly initiated by HPA staff and staff from the London hospitals' Infection Control Teams. Close contacts were followed up for a period of 10 days from the date of last exposure to the index case. If contacts developed respiratory illness in this period, they were asked to self-isolate in their homes (or were isolated in hospital if requiring admission).

The hospital in Qatar was informed to allow them to initiate appropriate follow-up for those who had been in contact with the patient.

HPA rapidly developed and published advice to health professionals, the public and travellers [5]. The case was immediately reported under the International Health Regulations to the World Health Organisation and through the European Union Early Warning and Response System (EWRS). Extensive laboratory work was undertaken to characterise the virus and develop new diagnostic tools [3].

Initial epidemiological investigation and preliminary findings
Close contacts of the case were followed up to determine the transmissibility of this novel coronavirus. This included collection of information on clinical illness, virological swabbing of contacts who had respiratory symptoms, and collection of paired sera from all contacts to determine whether there was evidence of recent infection.

It is likely that the patient's infection was acquired in Qatar as he was in Qatar for the 16 days prior to the onset of his most recent respiratory illness in September [2012]. The earlier, mild upper respiratory tract infection, which began during his visit to Saudi Arabia, resolved 2 weeks before onset of the present illness.

By [4 Oct 2012], tracing of contacts had identified 64 persons, among healthcare workers, family and friends, who were reported to have been in close contact with the confirmed case while he was symptomatic in the UK (Figure 2). Ten days after the date of last respective exposure, none of the close contacts had developed severe respiratory disease requiring hospital admission. Interim results have identified 13 close healthcare worker contacts with mild, self-limiting respiratory symptoms. These contacts were self-isolated in their homes until asymptomatic. In addition, one hospitalised patient who had potential contact with the case and subsequently became unwell was identified and subsequently tested negative using a pan-coronavirus assay [4]. The novel coronavirus has not been detected in any of the 10 symptomatic healthcare worker contacts tested by [4 Oct 2012].

Four possible cases with a history of recent travel from Saudi Arabia or Qatar have also been identified and investigated in the UK since active case finding commenced. Although the likelihood of novel coronavirus infection in any of these was considered low, strict infection control measures were taken. For 3 of them, samples were available, and the novel coronavirus was not detected. A 4th case, who died at the beginning of September [2012], remains under investigation.

Figure 2. Outcome of close contact follow-up 10 days or more since last exposure to index case with a novel coronavirus infection, London, September 2012 (n=64) [available at above URL link]

Public health implications
We present a case of severe respiratory illness resulting from a novel coronavirus acquired in the Middle East. The clinical picture is similar to that of a case previously described from Saudi Arabia and caused by a closely related virus. Although cases of SARS, for which the causative agent SARS-CoV is in the same group of coronaviruses, were reported with incubation periods beyond 10 days, 95 percent were reported to have an incubation period of less than 10 days [6]. In the light of this finding, the case of novel coronavirus that we report appears to have been acquired in Qatar based on the known time course of the patient's infection and other available information, unless the illness had an unusual biphasic nature or a very long incubation period.

After 10 days of follow-up, there has been no confirmed evidence of ongoing person-to-person transmission resulting in severe disease or milder laboratory confirmed infection among close contacts, despite extensive active contact tracing. Completion of case-contact investigation, including serological testing when available, will determine whether mild or asymptomatic infection among close contacts has occurred. In addition, serological investigation in the countries of origin of the 2 confirmed cases should be considered to look for evidence of possible previous infection in the general population. Studies in animals are also necessary to determine whether there is an animal reservoir for this infection and what it might be.

Early detection and investigation of cases of severe respiratory illness among travellers returning from countries where infection with novel coronavirus has been reported and their close contacts will support the further elucidation of the epidemiological characteristics of this novel virus. An outbreak of severe respiratory illness of unknown aetiology was reported from the Middle East earlier in 2012 [7]. Work needs to be undertaken to determine whether a novel coronavirus has been circulating more widely in the general population in the Middle East already for some time or whether the virus was more recently introduced from an unknown animal reservoir.

References:
1. World Health Organization (WHO). WHO final summary SARS, 15 August 2003: Summary table of SARS cases by country, 1 November 2002 - 7 August 2003. Geneva; WHO; 2003. Available from: http://www.who.int/csr/sars/country/2003_08_15/en/index.html
2. ProMED-mail. Novel coronavirus - Saudi Arabia: human isolate. Archive Number: 20120920.1302733. 20 September 2012. Available from: http://www.promedmail.org/?p=2400:1000
3. Corman VM, Eckerle I, Bleicker T, Zaki A, Landt O, Eschbach-Bludau M, et al. Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction. Euro Surveill. 2012;17(39):pii=20285. Available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20285
4. Bermingham A, Chand MA, Brown CS, Aarons E, Tong C, Langrish C, et al. Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United Kingdom from the Middle East, September 2012. Euro Surveill. 2012;17(40):pii=20290. Available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20290
5. Health protection Agency (HPA). Algorithm for investigation and management of possible cases of severe acute respiratory illness associated with a novel coronavirus. London; HPA; 2012. Available from: http://www.hpa.org.uk/webw/HPAweb&Page&HPAwebAutoListName/Page/1317136202637
6. Lessler J, Reich NG, Brookmeyer R, Perl TM, Nelson KE, Cummings DA. Incubation periods of acute respiratory viral infections: a systematic review. Lancet Infect Dis. 2009; 9(5):291-300. [abstract available at: http://www.ncbi.nlm.nih.gov/pubmed/19393959]
7. European Centres for Disease Control (ECDC). Communicable Disease Threats Report (Week 18, 29 April-5 May 2012). Stockholm; ECDC: 2012 Available from: http://ecdc.europa.eu/en/publications/Publications/CDTR%20online%20version%204%20May%202012.pdf

[Reported by: R G Pebody1, M A Chand1, H L Thomas1,2,3, H K Green1, N L Boddington1, C Carvalho1,3, C S Brown1, S R Anderson1, C Rooney1, E Crawley-Boevey1, D J Irwin1, E Aarons4, C Tong4, W Newsholme4, N Price4, C Langrish4, D Tucker4, H Zhao1, N Phin1, J Crofts1, A Bermingham1, E Gilgunn-Jones1, K E Brown1, B Evans1, M Catchpole1, J M Watson1
1. Health Protection Agency (HPA), London, United Kingdom
2. Field Epidemiology Training Programme (FETP), Health Protection Agency, London, United Kingdom
3. European Programme for Intervention Epidemiology Training (EPIET), European Centre for Disease Prevention and Control, (ECDC), Stockholm, Sweden
4. Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, United Kingdom]

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[2] UK - Clinical and laboratory findings, Eurosurveillance
Date: 4 Oct 2012
Source: Eurosurveillance, Volume 17, Issue 40 [edited]
http://eurosurveillance.org/ViewArticle.aspx?ArticleId=20290

Rapid communications
Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United Kingdom from the Middle East, September 2012
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Coronaviruses have the potential to cause severe transmissible human disease, as demonstrated by the severe acute respiratory syndrome (SARS) outbreak of 2003. We describe here the clinical and virological features of a novel coronavirus infection causing severe respiratory illness in a patient transferred to London, United Kingdom from the Gulf region of the Middle East.

Introduction
Coronaviruses are recognised causes of mild respiratory tract infections in humans, 1st identified in the 1960s [1]. These large RNA viruses affect a wide range of animals including domestic and companion animals and bats [2]. Limited surveillance data show that bats host the greatest diversity of coronaviruses, varying by region and species [3], suggesting that they may be the natural reservoir.

The severe acute respiratory syndrome (SARS) outbreak of 2003 -- affecting over 8000 people across 3 continents with a case fatality ratio of about 10 percent [4] -- indicates the potential of an animal coronavirus to jump species and transmit from person to person causing severe illness. This experience has raised awareness of the potential threat from zoonotic coronaviral infections and the need to adopt strict infection control measures when such cases are found, especially in healthcare settings.

Case history
On [14 Sep 2012], the United Kingdom Health Protection Agency (HPA) Imported Fever Service was notified of a case of unexplained severe respiratory illness in a London intensive care unit. The patient had recently transferred from Qatar and had a history of travel to Saudi Arabia.

He was a previously well 49-year-old man who developed a mild undiagnosed respiratory illness while visiting Saudi Arabia during August 2012, which fully resolved. He subsequently presented to a physician in Qatar on [3 Sep 2012] with cough, myalgia and arthralgia and was prescribed oral antibiotics. Five days later, he was admitted to a Qatari hospital with fever (38.4 C) and hypoxia, with oxygen saturation of 91 percent on room air. A chest X-ray showed bilateral lower zone consolidation. He was treated with ceftriaxone, azithromycin and oseltamivir. After 48 hours, he required intubation and ventilation and was transferred by air ambulance to London. During transfer, he was clinically unstable, requiring manual ventilation.

On admission to intensive care in London, he remained severely hypoxic, achieving an arterial PaO2 of 6.5 kPA (normal range: 11-13 kPA) on 100 percent oxygen with optimised pressure ventilation, and required low-dose norepinephrine to maintain blood pressure. His white blood cell count was 9.1 x 109/L (normal range: 4-11 x 109/L), C-reactive protein 350 mg/L (normal range: 0-10 mg/L) and creatinine 353 micro mol/L (normal range: 53-97 micro mol/L), with normal liver function and coagulation. He was treated with corticosteroids and broad-spectrum antibiotics, initially meropenem, clarithromycin and teicoplanin. Colistin and liposomal amphotericin B were subsequently added.

His condition deteriorated between [11 and 20 Sep 2012], with progressive hypoxia. His C-reactive protein level peaked at 440 mg/L and procalcitonin at 68 ng/ml (normal level: less than 0.5 ng/ml). His renal function worsened, and haemofiltration was initiated on [14 Sep 2012]. He was transferred to a specialist intensive care unit, and on [20 Sep 2012] (day 17 of illness), extracorporeal membrane oxygenation (ECMO) was started. As of [2 Oct 2012], he remains stable but fully dependent on ECMO after 13 days (day 30 of illness).

Diagnostic approach
Microbiological diagnostics in Qatar and London were used to look initially for common viral and bacterial causes of severe respiratory illness and subsequently for pathogens endemic in the Middle East (Table 1). By mid-September [2012], the syndrome was considered most compatible with viral pneumonia. Upper and lower respiratory tract samples were sent to the HPA Respiratory Virus Unit for extended influenza testing; all were negative. On [20 Sep 2012], a ProMED-mail report described a novel human coronavirus recovered from an adult male Saudi Arabian who died in June 2012 following acute respiratory illness, pneumonia, and renal failure [5]. The Erasmus Medical Center (the Netherlands) had sequenced the virus and identified it as a previously undescribed coronavirus related to known bat coronaviruses. Given that the patient described in our report had travelled to Saudi Arabia, HPA, in consultation with local clinicians, decided to investigate samples from the patient for the presence of the novel coronavirus.

Table 1. Microbiological investigations performed on London patient with novel coronavirus infection, September 2012 [see above given URL link]

Detection of a novel coronavirus
We used real-time PCR on upper (nose and throat swabs) and lower respiratory tract samples (sputum and tracheal aspirates) to test for a range of coronaviruses: OC43, 229E, NL63 and SARS-CoV. We also used a block-based pan-coronavirus PCR with degenerate primers targeted to the conserved RNA-dependent RNA polymerase (RdRp Pol) gene that detects all coronaviruses known to infect humans and a range of animal coronaviruses [6]. The pan-coronavirus assay yielded a band of the correct size in lower respiratory tract samples, but the assays for OC43, 229E, NL63 and SARS-coronaviruses were negative. Sanger sequencing of the pan-coronavirus PCR product (a 251 base pair fragment encompassing nucleotides 104-354 of the NSP12 gene) yielded a sequence that on BLAST analysis gave genetic identity of 81 percent to bat coronavirus/133/2005 (GenBank accession number DQ648794.1) and 75 percent identity to porcine haemagglutinating encephalomyelitis virus strain VW572 (GenBank accession number DQ011855.1) The sequence identified is available on the HPA website [7]. In response to this identification, a new set of real-time RT PCR assays were developed [8]. The results of these assays tested on novel coronavirus tissue culture material and clinical samples from this confirmed case are shown in Table 2.

Table 2. Real-time PCR results of coronavirus samples, September 2012 [see above given URL link]

On the basis of the sequence obtained, a maximum likelihood tree (Figure [see above given URL link]) showed that the virus belongs to the genus _Betacoronavirus_, with closest relationships to bat coronaviruses HKU4 and HKU5. Viruses that share more than 90 percent sequence identity in the conserved replicase domain are considered to belong to the same species by the International Committee on Taxonomy of Viruses (ICTV). Our sequence comparisons suggested that the virus nucleic acid fragment identified is derived from a novel coronavirus that is distinct from all coronaviruses described to date.

Figure. Phylogenetic relationships of partial sequences from the polymerase gene (nsp12) of the coronavirus sequence obtained at the Health Protection Agency, together with representative coronaviruses from different groups [see above given URL link]

A total of 13 close contacts of the index case were identified who had developed mild self-limiting respiratory illnesses since exposure to the case [8]. Ten of these have had nose and throat swabs tested by pan-coronavirus assay, and the novel coronavirus was not detected.

Discussion
Ascribing viral taxonomy on the basis of a small segment of sequence representing less than one percent of a viral genome is highly presumptive. However, the replicase genes are extremely conserved within coronaviruses, and the gene targeted by the pan-coronavirus assay is highly correlated with taxonomic classification based on the whole genome [9], confirming the choice of assay and the validity of the phylogeny [see Figure at above given URL link]. Final allocation of taxonomy and nearest neighbour relatedness will require more extensive sequence obtained either through genomic analysis of virus isolates cultured from the available clinical material or more extensive partial genome sequence derived directly from clinical material if virus isolation is not possible.

While most coronaviral infections of humans cause mild illness, zoonotic transmission of animal coronaviruses such as SARS-CoV can cause severe illness and death. Preliminary data sharing (Ron Fouchier, personal communication, [23 Sep 2012]) indicates 99.5 percent identity over the region of the replicase compared with the virus isolated from the patient in Saudi Arabia and described in ProMED-mail. This is confirmed by the publication of the whole genome sequence (GenBank accession number JX869059.1). On the basis of the clinical and virological features, we believe that the fragment of coronaviral sequence we have recovered represents a novel human coronavirus causing a severe respiratory illness.

The rapid development of sensitive and specific molecular diagnostics for new organisms is facilitated by sharing information and data between laboratories with different capabilities or reagents. The initial molecular approaches used in this case were part of a broad screening approach based on experience gained during the response to SARS. The development of specific diagnostics for the novel coronavirus will improve sensitivity and enable rapid exclusion or identification of potential clinical cases.

The origin for this novel virus is unknown. Epidemiological human and animal investigations in the region of origin are required to distinguish between an animal reservoir that either directly or indirectly transmits the virus occasionally to humans, and a previously unrecognised endemic infection of humans that causes severe outcomes in a few of those infected. Distinguishing between these possibilities will require wider application of more specific and sensitive molecular assays for coronaviruses and greater awareness of the possible presence of coronaviruses in human acute severe respiratory illness. Extensive serological testing of potentially exposed human populations and contacts will be a key indicator of the extent of disease due to novel coronaviruses.

References
1. Tyrrell DA, Bynoe ML. Cultivation of a novel type of common-cold virus in organ cultures. Br Med J. 1965;1(5448):1467-70. [article available at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2166670/pdf/brmedj02397-0043.pdf]
2. Shi Z, Hu Z. A review of studies on animal reservoirs of the SARS coronavirus. Virus Res. 2008;133(1):74-87. [abstract available at: http://www.ncbi.nlm.nih.gov/pubmed/17451830]
3. Anderson LJ, Tong S. Update on SARS research and other possibly zoonotic coronaviruses. Int J Antimicrob Agents. 2010;36 Suppl 1:S21-5. [article available at: http://www.ijaaonline.com/article/S0924-8579(10)00257-8/fulltext]
4. World Health Organization (WHO). Summary table of SARS cases by country, 1 November 2002 - 7 August 2003. Geneva: WHO; 15 Aug 2003. [available from: http://www.who.int/csr/sars/country/2003_08_15/en/index.html]
5. ProMED mail. Novel coronavirus - Saudi Arabia: human isolate. Archive Number: 20120920.1302733. [available from: http://www.promedmail.org/?p=2400:1000]
6. Bermingham A, Heinen P, Iturriza-Gomara M, Gray J, Appleton H, Zambon MC. Laboratory diagnosis of SARS. Philos Trans R Soc Lond B Biol Sci. 2004;359(1447):1083-9. [article available at: http://rstb.royalsocietypublishing.org/content/359/1447/1083.full.pdf+html]
7. Health Protection Agency (HPA). Partial genetic sequence information for scientists about the novel coronavirus 2012. London: HPA. [Accessed 2 Oct 2012]. [available from: http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/NovelCoronavirus2012/respPartialgeneticsequenceofnovelcoronavirus/]
8. Pebody RG, Chand MA, Thomas HL, Green HK, Boddington NL, Carvalho C, et al. The United Kingdom public health response to an imported laboratory confirmed case of a novel coronavirus in September 2012. Euro Surveill. 2012;17(40):pii=20292. [available from: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20292]
9. Drexler JF, Gloza-Rausch F, Glende J, Corman VM, Muth D, Goettsche M, et al. Genomic characterization of severe acute respiratory syndrome-related coronavirus in European bats and classification of coronaviruses based on partial RNA-dependent RNA polymerase gene sequences J Virol. 2010;84(21):11336-49. [article available at: http://jvi.asm.org/content/84/21/11336.full]
10. Corman VM, Eckerle I, Bleicker T, Zaki A, Landt O, Eschbach-Bludau M, et al. Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction. Euro Surveill. 2012;17(39):pii=20285. [available online: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20285].

[Reported by: A Bermingham1, M A Chand1, C S Brown1, E Aarons2, C Tong2, C Langrish2, K Hoschler1, K Brown1, M Galiano1, R Myers1, R G Pebody1, H K Green1, N L Boddington1, R Gopal1, N Price2, W Newsholme2, C Drosten3, R A Fouchier4, M Zambon1
1 Health Protection Agency (HPA), London, United Kingdom
2 Guy's and St Thomas' NHS Foundation Trust and King's Health Partners, London, United Kingdom
3 Institute of Virology, University of Bonn Medical Centre, Bonn, Germany
4 Department of Virology, Erasmus Medical Centre, Rotterdam, the Netherlands]

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[3] Saudi Arabia - ongoing investigations, newswire
Date: 4 Oct 2012
Source: Ottawa Citizen [edited]
http://www.ottawacitizen.com/health/Expert+teams+Saudi+Arabia+looking+source+coronavirus/7339897/story.html

A couple of teams of disease experts have converged on Saudi Arabia, hoping to find the source of a new virus from the SARS family.

Experts from the World Health Organization and the Center for Infection and Immunity at Columbia University in New York are in Riyadh on the invitation of the Saudi government, a senior health ministry official confirmed Wednesday [3 Oct 2012].

The Columbia team includes virologist Dr. Ian Lipkin, who was described as "the world's most celebrated virus hunter" by Discover magazine in a profile earlier this year [2012]. It also includes 2 experts from EcoHealth, a New York City-based international organization for ecology and health.

A team from the U.S. Centers for Disease Control in Atlanta is also slated to arrive next week, though Dr. Ziad Memish, Saudi Arabia's deputy minister of health, said those plans may change if no new cases of the disease come to light in coming days.

"If we feel that there's a need, of course we'll continue with the mission," Memish said in an interview. "If we feel that things are being covered, and things continue to be stable, we're not saying we would cancel the team, but maybe we would delay it. We will have to review things every day."

To date, there have only been 2 confirmed cases of infection with the new coronavirus, one in a man from Saudi Arabia and another from Qatar. The Saudi man died in June [2012]. The man from Qatar was sent by air ambulance to Britain, where he remains in serious condition in a hospital in London. In both cases the disease triggered both severe respiratory illness and kidney failure.

With 2 cases from 2 countries and several months between them, finding the source of the new virus will be a challenge, said Dr. Donald Low, an infectious diseases expert from Toronto's Mount Sinai Hospital. "I bet it would be pretty difficult. Otherwise, the answer may have been obvious by now," said Low, who was one of the key figures in Toronto's fight against SARS in 2003.

The new virus is a member of the family of coronaviruses, a large group which infects animals, birds and humans. Several of the human coronaviruses cause mild respiratory illness, essentially colds.

But at the other end of the disease spectrum was the virus responsible for severe acute respiratory syndrome -- SARS -- which infected 8422 people and killed 916 in late 2002 and 2003. That's a case fatality rate of nearly 11 per cent.

The emergence of the new virus comes at a delicate time, with Muslims from around the world arriving in Saudi Arabia for Hajj, the annual Islamic pilgrimage to Mecca.

It's estimated that 3 million people will take part in this year's [2012] Hajj, and Memish said half a million have already arrived in the country. This year's Hajj starts on [24 Oct 2012].

Concern over the possibility of an outbreak during Hajj was one of the reasons why 3 outside groups of disease detectives were asked for assistance. But Memish said the lack of evidence of spread of the illness from the cases to their contacts and health-care workers is easing concerns.

As for the possible sources of the virus, it's thought that animals found in the region may harbour the pathogen. Camels and goats have been named as a couple of possible sources.

Memish was vague when asked whether the man who died had contact with animals. "We have some information, yes, but the information is not complete yet. Once the information is out, we will announce it," he said, adding the teams are looking at both animals and the Saudi man's environment.

[Byline: Helen Branswell]

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[4] USA - current recommendations, MMWR
Date: 4 Oct 2012
Source: MMWR Early Release 4 Oct 2012 / 61(Early Release);1-2 [edited]
http://www.cdc.gov/mmwr/preview/mmwrhtml/mm61e1004a1.htm?s_cid=mm61e1004a1_e

Severe Respiratory Illness Associated with a Novel Coronavirus -- Saudi Arabia and Qatar, 2012
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CDC is working closely with the World Health Organization (WHO) and other partners to better understand the public health risk presented by a recently detected, novel coronavirus. This virus has been identified in 2 patients, both previously healthy adults who suffered severe respiratory illness (1,2). The 1st patient, a man aged 60 years from Saudi Arabia, was hospitalized in June 2012 and died; the 2nd patient, a man aged 49 years from Qatar with onset of symptoms in September 2012 was transported to the United Kingdom for intensive care. He remains hospitalized on life support with both pulmonary and renal failure (3,4). Person-to-person or health-care-associated transmission has not been identified to date (5). Interim case definitions based on acute respiratory illness and travel history were issued by WHO on [29 Sep 2012] and include criteria for "patient under investigation," "probable case," and "confirmed case" (6). This information is current as of [4 Oct 2012]. Updates on the investigation and the WHO case definition are available at http://www.who.int/csr/don/en/index.html.

Coronaviruses are a large, diverse group of viruses that affect many animal species. A few of these viruses cause a wide range of respiratory illness in humans, typically with "common cold" symptoms. Genetic sequence data indicate that this new virus is a beta-coronavirus similar to bat coronaviruses but not similar to any other coronavirus previously described in humans, including the coronavirus that caused severe acute respiratory syndrome (SARS) (1). Comparison of viral genetic sequences from the 2 patients indicated that the 2 viruses are closely related. Treatment is supportive because no specific therapy has been shown to be effective.

WHO and CDC have not issued any travel alerts at this time. The risk to U.S. residents traveling in the region currently is estimated to be low. For persons traveling to Saudi Arabia to participate in the Hajj, scheduled for [24-29 Oct 2012], requirements and recommendations remain unchanged and can be found at http://www.cdc.gov/features/Hajj.

Persons who develop acute respiratory illness within 10 days after returning from Saudi Arabia or Qatar (excluding persons who only passed through airports) should consult a physician and mention their recent travel. Persons with acute severe lower respiratory illness requiring hospitalization should be evaluated using the guidance at the CDC coronavirus website (http://www.cdc.gov/coronavirus/ncv), which is based on the WHO case definition. Persons whose respiratory illness remains unexplained and who meet the WHO criteria for "patient under investigation" should be reported immediately to CDC through state and local health departments. At present, testing of specimens for the novel coronavirus will be conducted by CDC; widely available diagnostic tests for coronaviruses are not suitable for detecting this new virus.

Recommendations and guidance on the case definitions, infection control including personal protective equipment, case investigation, and specimen collection and shipment, are available at the CDC coronavirus website. Because of the possibility of frequent updates as new information becomes available, readers are encouraged to consult the CDC coronavirus website for current information. State and local health departments with questions should contact the CDC Emergency Operations Center ( 770-488-7100).

[Reported by: Div of Viral Diseases, National Center for Immunization and Respiratory Diseases; Div of Healthcare Quality Promotion, Div of Global Migration and Quarantine, National Center for Emerging and Zoonotic infectious Diseases; Div of Global Disease Detection and Emergency Response, Center for Global Health; Eyal Leshem, MD, EIS Officer, CDC. Corresponding contributor: Eyal Leshem <eleshem@cdc.gov> 404-639-7251.]

References:
1. Corman VM, Eckerle I, Bleicker T, et al. Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction. Euro Surveill 2012;17(39).
2. Danielsson N, on behalf of the ECDC Internal Response Team, Catchpole M. Novel coronavirus associated with severe respiratory disease: case definition and public health measures. Euro Surveill 2012;17(39).
3. Bermingham A, Chand MA, Brown CS, et al. Severe respiratory illness caused by a novel coronavirus, in a patient transferred to the United Kingdom from the Middle East, September 2012. Euro Surveill 2012;17(40).
4. European Centre for Disease Prevention and Control (ECDC). Rapid risk assessment: severe respiratory disease associated with a novel coronavirus. Stockholm, Sweden: ECDC; 2012. [available at: http://ecdc.europa.eu/en/publications/Publications/RRA-. Novel-coronavirus-final20120924.pdf]. Accessed October 4, 2012.
5. Pebody RG, Chand MA, Thomas HL, et al. The United Kingdom public health response to an imported laboratory confirmed case of a novel coronavirus in September 2012. Euro Surveill 2012;17(40) [available at: http://eurosurveillance.org/ViewArticle.aspx?ArticleId=20292]
6. World Health Organization. Global alert and response (GAR): revised interim case definition--novel coronavirus. Geneva, Switzerland: World Health Organization; 2012. [available at: http://www.who.int/csr/disease/coronavirus_infections/case_definition/en/index.html, accessed October 4, 2012].

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Communicated by:
ProMED-mail
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[The above reports highlight the importance of early dissemination of information on novel organisms identified by laboratories when investigating undiagnosed severe illnesses. The report of the identification of a novel coronavirus in specimens from a fatal case of severe respiratory disease with renal failure was seen by healthcare professionals treating another case of severe respiratory disease with renal failure in a patient coming from the same geographic region and led to the identification of a novel coronavirus genetically related to the 1st reported case. Once again, the astute healthcare personnel searching for a diagnosis for a seriously ill patient read the 1st report and recognized the epidemiologic and clinical links with another case elsewhere.

Unfortunately, not all novel pathogens are reported this quickly. Oftentimes, they are held pending publication in peer-review journals (a review of ProMED-mail archives for 1st reports of novel pathogens will highlight this observation). Historically, countries were reluctant to announce novel pathogens for fear of economic repercussions, trade quarantines, reduced tourism, and business related travel.

The importance of background serosurveys in the countries of presumed infection of these 2 cases (Saudi Arabia and Qatar) cannot be overemphasized. At present, there are 2 reported cases of severe respiratory disease with renal failure from whom a genetically similar novel coronavirus was isolated. Serosurveys among persons living in the same geographic areas of these 2 cases will help determine the background prevalence of infection with this novel coronavirus, and serosurveys of non-human animals in the areas will help identify possible animal reservoirs. In addition, more in-depth investigations surrounding the contacts of the case in Saudi Arabia (at present the "index case") as mentioned in the newswire in part [3] above will be forthcoming and may shed more light on the epidemiology of this novel coronavirus.

If one looks at the interactive HealthMap/ProMED map showing the location of Saudi Arabia and Qatar, (see http://healthmap.org/r/1HAJ), one sees the proximity of Qatar to Saudi Arabia. According to the reports posted, the patient was hospitalized in Jeddah, in the Western part of Saudi Arabia, whereas Qatar is immediately to the east of Saudi Arabia. - Mod.MPP]

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