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Published Date: 2012-09-28 10:48:09
Subject: PRO/AH/EDR> Novel coronavirus - Saudi Arabia (07): Eurosurveillance reports
Archive Number: 20120928.1313337

NOVEL CORONAVIRUS - SAUDI ARABIA (07): EUROSURVEILLANCE REPORTS
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In this post:
[1] Eurosurveillance editorial observations
[2] ECDC/HPA report & recommendations

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[1] Eurosurveillance editorial observations
Date: Thu 27 Sep 2012
Source: Eurosurveillance Edition 2012, 17(39) [edited]
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20284

Note from the editors: A new virus bringing back memories from the past
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[Reported by: Eurosurveillance editorial team (<eurosurveillance@ecdc.europa.eu>) 1
1. European Centre for Disease Prevention and Control (ECDC), Stockholm, Sweden]

In recent days, public health experts and healthcare workers around the world are alert following the discovery of a new human coronavirus causing severe respiratory illness. 2 cases, both with connection to Saudi Arabia, were communicated through [ProMED-mail on 20 and 23 Sep 2012] respectively [1,2].

Many health professionals still have vivid memories of the alert that followed the death of an American businessman in a hospital in Hanoi, Viet Nam, in early 2003 after having travelled to China, and the following outbreak of severe acute respiratory syndrome (SARS). This triggered worldwide alarm and containment measures. During the outbreak, there was excellent collaboration between global players and institutions, on various levels (that is, public health institutions, laboratories, and hospitals) and new ways of communicating proved to be highly value for the exchange of information. The last case of SARS occurred in China in May 2004: thereafter the virus seemed to have disappeared and has not resurfaced since.

The public health world is currently looking closely into the 2 recent cases of coronavirus infection. Similar to SARS, the 2 patients had/have symptoms of severe respiratory illness and the virus comes from the same family, _Coronaviridae_. However, there are some marked differences. The virus is not the same: laboratory analyses have proven that the new virus is not a SARS-like virus. Furthermore, the 2 confirmed cases occurred with a gap of 3 months between them and there is no evidence of a direct epidemiological link.

Much remains unknown at the moment and information that would allow us to make a final judgment about the disease is missing. 2 rapid communications in this issue [see below] give a timely account of the recommended public health measures and assays to detect the virus. On the basis of the limited evidence currently available, the risk for person-to-person transmission, as assessed by the European Centre for Disease Prevention and Control (ECDC) in a rapid risk assessment, is considered low [3]. Eurosurveillance will continue to provide more information as it becomes available.

["Detection of a novel human coronavirus by real-time reverse-transcription polymerase chain reaction; http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20285 and
"Novel coronavirus associated with severe respiratory disease: Case definition and public health measures"; http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20282. - Mod.MPP]

References
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1. ProMED-mail: Novel coronavirus - Saudi Arabia: human isolate. Archive Number: 20120920.1302733. 20 Sep 2012. Available from http://www.promedmail.org/direct.php?id=20120920.1302733
2. ProMED-mail: Novel coronavirus - Saudi Arabia (03): UK HPA, WHO, Qatar. Archive Number: 20120923.1305982. 23 Sep 2012. Available from http://www.promedmail.org/direct.php?id=20120923.1305982
3. European Centre for Disease Prevention and Control (ECDC): Severe respiratory disease associated with a novel coronavirus, 24 Sep 2012. Rapid risk assessment. Stockholm: ECDC; 2012. Available from http://www.ecdc.europa.eu/en/publications/Publications/RRA-Novel-coronavirus-final20120924.pdf

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[2] ECDC/HPA report & recommendations
Date: Thu 27 Sep 2012
Source: Eurosurveillance Edition 2012, 17(39) [edited]
http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20282

Novel coronavirus associated with severe respiratory disease: case definition and public health measures
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[Reported by: N Danielsson 1, on behalf of the ECDC Internal Response Team 2, M Catchpole 3
1. European Centre for Disease Prevention and Control, Stockholm, Sweden
2. The ECDC internal response team: K Leitmeyer, P Kinross, H Zeller, N Danielsson, P Penttinen, R Snacken, A-P Magiorakos, A Ozin, R Jain, E Robinson, L P Hellstrom, A Nicoll, J Jansa, and D Coulombier.
3. Health Protection Agency, London, UK]

2 cases of rapidly progressive acute respiratory infection in adults associated with a novel coronavirus have generated an international public health response. The 2 infections were acquired 3 months apart, probably in Saudi Arabia and Qatar. An interim case definition has been elaborated and was published on the World Health Organization website on [25 Sep 2012].

Case 1
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On [13 Jun 2012] a [60-year-old patient] presented with deteriorating pneumonia in Jeddah, Saudi Arabia and a 7 day history of respiratory symptoms. The patient developed acute renal failure and died on [24 Jun 2012]. A novel beta-coronavirus was isolated and sequenced at the Erasmus Medical Centre (EMC) in Rotterdam, the Netherlands [1].

Case 2
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On [11 Sep 2012] a [49-year-old patient] with severe respiratory symptoms was evacuated from Qatar to a United Kingdom hospital and was admitted to intensive care there on [12 Sep 2012]. The patient remains in hospital and has been on life support with pulmonary and renal failure. Extensive diagnostic tests for a causative agent were negative but on [21 Sep 2012] a pan-coronavirus RT-PCR test performed on lower respiratory samples was positive for a conserved sequence of the coronavirus polymerase gene [2]. Comparison with the nucleotide sequence at the EMC indicated a close match with the novel virus isolated from Case 1. Contacts of Case 2, many of them healthcare workers, are being actively identified, monitored, and investigated for coronavirus infection. Some of them have reported mild respiratory symptoms but none have tested positive for the novel virus or developed severe disease to date [3].

Background
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Coronaviruses are globally distributed and are found in humans, other mammals, and birds. They are enveloped RNA viruses classified in alpha, beta, and gamma genera. Up to one third of mild upper respiratory tract infections in adults are caused by human coronaviruses. The zoonotic severe acute respiratory syndrome (SARS) beta-coronavirus (SARS-CoV) caused the SARS outbreak in 2003 when over 900 people died. [4] Human coronaviruses are transmitted through direct contact with secretions and via aerosol droplets. Infected patients also excrete virus in faeces and urine and under certain circumstances, airborne transmission can occur from aerosolised respiratory secretions and faecal material [5].

The detection of a novel coronavirus associated with severe respiratory disease and renal failure requires urgent assessment and careful management. The United Kingdom Health Protection Agency (HPA) alerted European Union (EU) Member States and other countries via the Early Warning and Response System (EWRS) and International Health Regulations (IHR) mechanisms.

Control measures
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The HPA has recommended stringent control measures and developed an early case definition [6]. The European Centre for Disease Prevention and Control (ECDC) has developed a risk assessment in response to the cases [2]. A surveillance strategy has been agreed between ECDC and WHO with the 1st priority being to determine whether there are additional severe cases. The initial virology results and the separation in time of the only 2 confirmed cases suggest an infection that quite probably is of zoonotic origin and different in behaviour from SARS [5]. It is essential to rule out there being additional severe undiagnosed cases, especially since the transfer of severely ill patients in air ambulances meant that cases may be missed by conventional surveillance that is based on clinical notification by the original diagnosing physician, particularly primary care physicians. Hence the interim case definition has been developed with the aim of providing a high level of sensitivity for identifying cases ill enough to require hospital care or having pneumonia while avoiding cases with only mild symptoms [7].

Case definition
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The case definition applies the established link that both cases stayed in the Arabian Peninsula but makes it conditional of hospitalisation or pneumonia, which means that cases with a link to an affected area but only mild symptoms do not require investigation. The affected area is currently defined as Saudi Arabia and Qatar but can be expanded as needed. Human coronaviruses have a short incubation period of 3 to 4 days. The longest incubation period observed during the SARS outbreak was 12 days. However, this was an outlier and a pragmatic incubation period of up to 10 days has been adopted for the case definition. The case definition should be used by clinicians for deciding which patients require investigation for possible novel coronavirus infection and which patients should be reported to national authorities. An interim case definition was published on the WHO website on [25 Sep 2012] [8]. It is expected to be amended once more epidemiological and diagnostic information becomes available and clinicians and public health managers should stay updated with the latest version on the website.

EU Member States have been requested to report patients meeting the case definition to ECDC through the EWRS and countries should continue to report probable or confirmed cases through the IHR [International Health Regulations] contacts at WHO regional offices as mandated by the IHR. There is currently no rapid diagnostic test that easily confirms infection with this novel virus. Virus detection and serological testing is being developed by the HPA, the EMC, and the University of Bonn, Germany and this was facilitated through close collaboration including the provision of preliminary sequences and a virus isolate between those institutions [9].

Infection control advice
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The HPA has developed specific infection control advice for suspected or confirmed novel coronavirus cases. The guidelines take a strict precautionary approach, whereby patients are isolated in negative-pressure single rooms or, if this is not possible then a single room with en-suite facilities. Full personal protective equipment (PPE), including gowns, gloves, and FFP3 masks are worn by staff and others having direct contact with the patient [6].

Conclusions
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This situation is still evolving and there are many unknowns to consider in hypothesis generation and control measures. There is strong evidence that a novel virus caused the severe disease in the 2 patients. Based on this assumption it can be concluded that the virus poses an as yet poorly defined level of threat to people's health. There may have been other cases in the past that were missed and serological testing of stored sera and other specimens from such cases will be important. Serological testing will also determine whether the 2 cases represent the most severe end of a spectrum of clinical presentations which also includes mild and asymptomatic infections or if they are isolated events. To date, the long period between occurrence of the 2 cases and the lack of secondary cases among contacts suggest the disease is poorly communicable in humans. Our assessment, based on the limited information currently available, is that the risk of wide-spread transmission resulting in severe disease is low. However, the emergence of a novel coronavirus requires a thorough assessment, which is currently being coordinated at international level.

References
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1. ProMED-mail: Novel coronavirus - Saudi Arabia: human isolate Archive Number: 20120920.1302733 20 Sep 2012. Available from http://www.promedmail.org/direct.php?id=20120920.1302733
2. European Centre for Disease Prevention and Control (ECDC): Rapid Risk Assessment. Severe respiratory disease associated with a novel coronavirus. Stockholm: ECDC; 2012. [Accessed 26 Sep 2012]. Available from http://ecdc.europa.eu/en/publications/Publications/RRA-Novel-coronavirus-final20120924.pdf
3. Health Protection Agency (HPA): HPA Press release. Acute respiratory illness associated with a new virus identified in the UK. London: HPA; 2012. [Accessed 25 Sep 2012]. Available from http://www.hpa.org.uk/NewsCentre/NationalPressReleases/2012PressReleases/120923acuterespiratoryillnessidentified/
4. World Health Organization (WHO): WHO final summary SARS, [15 Aug 2003]:Summary table of SARS cases by country, [1 Nov 2002-7 Aug 2003]. Geneva: WHO; 2003. Available from http://www.who.int/csr/sars/country/country2003_08_15.pdf
5. World Health Organization (WHO): Consensus document on the epidemiology of severe acute respiratory syndrome (SARS) 2003. Geneva: WHO; 2003. Available from http://www.who.int/csr/resources/publications/CDS_CSR_ARO_2004_2.pdf
6. Health Protection Agency (HPA): Infection control advice: Suspected or Confirmed Novel Coronavirus Cases. London: HPA; 2012. [Accessed 25 Sep 2012]. http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1317136232722
7. World Health Organization (WHO): WHO Case-finding interim case definition. Geneva: WHO; 2012. [Accessed 26 Sep 2012]. Available from http://www.who.int/csr/disease/coronavirus_infections/en/index.html
8. World Health Organization (WHO): Case definition for case finding severe respiratory disease associated with novel coronavirus. Geneva: WHO; 2012. Available from http://www.who.int/csr/disease/coronavirus_infections/en/index.html
9. Health Protection Agency (HPA). Partial genetic sequence information for scientists about the Novel Coronavirus 2012. London: HPA; 2012. [Accessed 25 Sep 2012]. Available from http://www.hpa.org.uk/Topics/InfectiousDiseases/InfectionsAZ/RespiratoryViruses/NovelCoronavirus/respPartialgeneticsequenceofnovelcoronavirus/

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[One of the most important conclusions reached in the discussions above is that current assessments are based on limited information currently available and there is the need to gather more information on the epidemiology of this novel coronavirus. As with prior outbreaks associated with newly identified organisms, initial reports of cases tend to be more severe clinical presentations -- with SARS in 2002/2003 the early reports were of many fatalities associated with identified cases. Similarly, the early reports of the 2009 influenza pandemic related to influenza A/H1N1 pdm09 virus were those of high numbers of deaths in previously healthy young individuals.

If one looks at the final epidemic curve for the SARS epidemic (available at http://www.who.int/csr/sars/epicurve/epiindex/en/index1.html) one is reminded that while the early reports of an outbreak of severe respiratory disease in Guangdong province, China, came to the attention of the international public health community in the 2nd week of February 2003, retrospective case finding during the course of the epidemic revealed individual cases had occurred with onset of illness beginning during the period of 22 Nov 2002 and continued to occur at a low level until January 2003.

Hence, caution is necessary before coming to definitive conclusions about this novel coronavirus until more information is known. - Mod.MPP]

See Also