Severe acute respiratory syndrome

Severe Acute Respiratory Syndrome (SARS) is an atypical form of pneumonia that first appeared in November 2002 in Guangdong Province, China. It spread to neighboring Hong Kong and Vietnam in late February 2003, and then to other countries via international travel of infected persons. SARS is fatal in about 10% of cases.

The mortality rate varies across countries and reporting organizations. In early May, for consistency with similar metrics of other diseases, the World Health Organization (WHO) and US Centers for Disease Control and Prevention was quoting 7%, or the number of deaths divided by probable cases, as the SARS mortality rate. Others spoke in favor of a 15% figure, derived from number of death divided by the number who recovered or died, saying it reflects the real situation more accurately. As the outbreak progressed both mortality measures approached 10%.

One reason for the difficulties in plotting a reliable mortality figure is that the number of infections and the number of deaths are increasing at completely different rates. A possible explanation involves a secondary infection as a causal agent in the disease (See Eric Lerner's analysis (http://www.politechbot.com/p-04718)), but whatever the cause, the mortality numbers are bound to change.

Mortality by age group as of May 8, 2003 is below 1% for people aged 24 or younger, 6% for those 25 to 44, 15% in those 45 to 64 and more than 50% for those over 65. [1] (http://www.who.int/csr/sarsarchive/2003_05_07a/en/)

For an ongoing timeline of the SARS outbreak, see Progress of the SARS outbreak.

Table of contents 1 Outbreak in China 2 Spread to other countries 3 Clinical information 3.1 Symptoms 3.2 Physical signs 3.3 Investigations 3.4 Diagnostic tests 3.5 Diagnosis 3.6 Treatment 4 Current state of etiologic knowledge of SARS 5 Mapping the genetic code of viruses linked to SARS 6 Progress of the outbreak 7 Action to try to control SARS 8 Political and economic reaction to SARS 9 SARS and accusations of racial discrimination 10 External links and references 10.1 Mainstream News 10.2 SARS Weblogs 10.3 Official Announcements 10.4 Medical Mailing Lists

Outbreak in China

SARS is now believed to be caused by the SARS virus, the discovery of which is documented below.

The virus appears to have originated in Guangdong province in November 2002, and despite taking some action to control the epidemic, the People's Republic of China failed to inform the World Health Organisation (WHO) of the outbreak until February 2003 and restricted coverage of the epidemic in order to preserve face and public confidence. This lack of openness has caused the PRC to take the blame for delaying the international effort against the epidemic. [2] (http://story.news.yahoo.com/news?tmpl=story2&cid=570&ncid=753&e=8&u=/nm/20030412/sc_nm/health_pneumonia_china_virus_dc) The PRC has since officially apologized for early slowness in dealing with the SARS epidemic. [3] (http://www.cnn.com/2003/HEALTH/04/05/sars.vaccine/index)

In early April, there appeared to be a change in official policy when SARS began to receive a much greater prominence in the official media. However, it was also in early April that accusations emerged regarding the undercounting of cases in Beijing military hospitals. After intense pressure, PRC officials allowed international officials to investigate the situation there. This has revealed major problems plaguing the aging mainland Chinese healthcare system, including increasing decentralization, bureaucratic red tape, and a lack of communication.

In late April, major revelations came to light as the PRC government admitted to underreporting the number of cases due to the problems inherent in the healthcare system. A number of PRC officials were fired from their posts, including the health minister and mayor of Beijing, and systems were set up to improve reporting and control in the SARS crisis. Since then, the PRC has taken a much more active and transparent role in combatting the SARS epidemic.

Spread to other countries

On March 12, 2003, the WHO issued a global alert, followed by a health alert by the United States Centers for Disease Control and Prevention (CDC).

The WHO reports that local transmission of SARS is taking place in Toronto, Singapore, Hanoi, Taiwan, and the Chinese regions of Guangdong, Hong Kong, and Shanxi. In Hong Kong the first batch of affected people were discharged from the hospital on March 29, 2003.

The Atlanta-based Centers for Disease Control (CDC) announced in early April their belief that a strain of coronavirus, possibly a strain never seen before in humans, is the infectious agent responsible for the spread of SARS. [4] (http://www.jhunewsletter.com/vnews/display.v/ART/2003/04/04/3e8e038cec7b6) Disease transmission is not well understood at this time. It is suspected to spread via inhalation of droplets expelled by an infected person when coughing or sneezing, or possibly via contact with secretions on objects. Health authorities are also investigating the possibility that it may be airborne, which would increase the potential contagiousness of the disease.

The chances that SARS-infected people could be "asymptomatic," meaning that carriers could be infectious without developing any of the tell-tale signs and hence move around within a population undetected, are small, WHO officials said. "If asymptomatic carriers were playing an important role we would see it by now," WHO spokesman Dick Thompson told Reuters.

Clinical information

Symptoms

Initial symptoms are flu-like, in that there can be any or all of the following symptoms: fever, myalgia, lethargy[?], gastrointestinal symptoms[?], cough, sore throat and other non-specific symptoms. The only symptom that is common to all patients appears to be a fever above 38 degrees Centigrade (100.4 degrees Fahrenheit). Later in the disease, susceptible patients will develop shortness of breath[?].

Symptoms usually appear 2-10 days (up to 13 days have been reported) after infection - in most cases symptoms appear around 2-3 days after infection. In about 10-20% of the cases, symptoms are so severe that patients have to be put on a ventilator[?].

Physical signs

Physical signs are inconclusive in early patients presenting with SARS. There may be no observable signs at all. Some patients will have tachypnoea or dyspnoea[?] or just plain shortness of breath[?]. Some patients in the early stage have some lung auscultation[?] findings which may be crackles[?] or crepitations[?] in any part of either lung. Later in the progression of the disease, tachypnoea and lethargy[?] become more prominent as the patients become more tired from the effort of breathing.

Investigations

The chest X-Ray[?] (CXR) appearance of SARS can vary quite significantly from patient to patient. There is no pathognomonic appearance of SARS but the common thread is that the CXR appears abnormal, usually with patchy infiltrates in any part of the lungs. Patients may initially present with a clear CXR but develop signs of SARS later.

The count of white blood cells and platelets is often low. Early findings suggest that there is a relative neutrophilia and a relative lymphopenia - relative because the total white count[?] itself tends to be low. Other suggestive laboratory tests are a raised lactate dehydrogenase[?] level and a slightly raised creatinine kinase[?] and C-Reactive protein[?] level.

Diagnostic tests

With the identification and sequencing of the DNA of the coronavirus supposedly responsible for SARS on April 12, 2003, several diagnostic test kits have been produced and are now being tested for their suitability for use.

Three possible diagnostic tests have emerged as top contenders but each one so far has its own drawbacks. The first, an ELISA (enzyme-linked immunosorbant assay[?]) test detects antibodies to SARS reliably but only 21 days after the onset of symptoms. The second, an immunofluorescence[?] assay, can detect antibodies 10 days after the onset of the disease but is a labour and time intensive test, requiring an immunoflourescence microscope and an experienced operator. The last test is a PCR (polymerase chain reaction) test that can detect genetic material of the SARS virus in specimens ranging from blood, sputum, tissue samples[?] and stool. The PCR tests so far have proven to be very specific[?] but not very sensitive[?]. This means that while a positive PCR test result is strongly indicative that the patient is infected with SARS, a negative test result does not mean that the patient does not have SARS.

The WHO has issued guidelines for using the various laboratory tests available to confirm the diagnosis of SARS [5] (http://www.who.int/csr/sars/labmethods/en/).

One current drawback is that there currently is no test that will allow for quick screening of patients on presentation in order to exclude SARS.

Research is ongoing in the development of a better laboratory [screening test].

Diagnosis

A suspected case of SARS is a patient who has any of the symptoms including a fever of 38 degrees Centigrade or more AND who has either a history of contact with someone with a diagnosis of SARS within the last 10 days OR travel to any of the regions identified by the WHO as areas with recent local transmission of SARS (affected regions as of 10th May, 2003 [6] (http://www.who.int/csr/sarsareas/2003_05_10/en/) are parts of China, Hong Kong, Singapore and the province of Ontario, Canada).

A probable case of SARS has the above findings plus positive chest x-ray findings of atypical pneumonia[?] or respiratory distress syndrome[?].

With the advent of diagnostic tests for the coronavirus probably responsible for SARS, the WHO has added the category of "laboratory confirmed SARS" for patients who would otherwise fit the above "probable" category who do not (yet) have the chest x-ray changes but do have positive laboratory diagnosis of SARS based on one of the approved tests (ELISA, immunofluorescence or PCR).

Treatment

So far, antibiotics have not proven to be effective. Treatment of SARS so far has been largely supportive with anti-pyretics, supplemental oxygen and ventilatory support as per necessary as the disease progresses. Any suspected cases of SARS be isolated, preferably in negative pressure[?] rooms, with full barrier nursing precautions taken for any necessary contact with these patients.

The use of steroids and the antiviral drug ribavirin were initially anecdotally alleged to be of use in treatment, but there has not been any published scientific evidence supporting this hypothesis. Many clinicians now believe that Ribavarin use had in fact worsened many patient's prognosis.

Researchers are currently testing all known antiviral treatments for other diseases including AIDS, hepatitis, influenza and others on the SARS-causing coronavirus to see if any of them has any significant effect.

There may be some benefit from using steroids and other immune system modulating agents in the treatment of the more acute SARS patients as there is some evidence that part of the more serious damage SARS causes is also due to the body's own immune system overreacting to the virus. Research is continuing in this area.

Current state of etiologic knowledge of SARS

The etiology of SARS is still being explored. On April 7, 2003, WHO announced that it was generally agreed that a newly identified coronavirus is the major causative agent of SARS, and that the significance of a human metapneumovirus (hMPV) in SARS remains unclear and would continue to be studied. [7] (http://www.who.int/csr/sars/findings/en/) This was followed by an announcement on April 16 that scientists at Erasmus University[?] in Rotterdam, the Netherlands have confirmed that the virus causing SARS is indeed the new coronavirus. In the experiments, monkeys were infected with the coronavirus, and it was observed that they developed the same symptoms as human SARS victims.

Initially, electron microscopic examination in Hong Kong and Germany found viral particles with structures suggesting paramyxovirus in respiratory secretions of SARS patients; subsequently, in Canada, electron microscopic examination found viral particles with structures suggestive of metapneumovirus[?] (a subtype of paramyxovirus) in respiratory secretions. Chinese researchers also reported that a chlamydia-like disease may be behind SARS. The Pasteur Institute[?] in Paris identified coronavirus in samples taken from six patients. The CDC, however, noted viral particles in affected tissue (finding a virus in tissue rather than secretions suggests that it is actually pathogenic rather than an incidental finding). On electron microscopy, these tissue viral inclusions resembled coronaviruses, and comparison of viral genetic material obtained by PCR with existing genetic libraries suggested that the virus was a previously unrecognized coronavirus. Sequencing of the virus genome--which computers at the British Columbia Cancer Agency in Vancouver completed at 4 a.m. Saturday, April 12, 2003--was the first step toward developing a diagnostic test for the virus, and possibly a vaccine. [8] (http://www.bayarea.com/mld/mercurynews/news/5629349.htm) A test was developed for antibodies to the virus, and it was found that patients did indeed develop such antibodies over the course of the disease, which is very suggestive that the virus does have a causative role. It is generally agreed that this coronavirus has a causative role in SARS: continued study is underway to test the hypothesis that co-infection with other organisms such as human metapneumovirus may also play a role.

An article published in The Lancet[?] identifies a coronavirus as the probable causative agent.

On April 16, 2003, the WHO issued a press release stating that the coronavirus identified by a number of laboratories was the official cause of SARS. [9] (http://www.who.int/mediacentre/releases/2003/pr31/en/)

In late May 2003, studies from samples of wild animals sold as food in the local market in Guangdong, China found that the SARS coronavirus could be isolated from civet cats. This suggests that the SARS virus crossed the species barrier[?] from civet cats; this conclusion is, however, by no means certain as it is certainly possible that the civet cats got the virus from humans and not the other way around or even that the civet cats are a sort of intermediary host. Further investigations are ongoing.[10] (http://straitstimes.asia1.com.sg/commentary/story/0,4386,191629,00)

Mapping the genetic code of viruses linked to SARS

On April 12, 2003, scientists working around the clock at the Michael Smith Genome Sciences Centre in Vancouver, British Columbia finished mapping the genetic sequence of a coronavirus believed to be linked to SARS. The team was lead by Dr. Marco Marra[?] and worked in collaboration with the British Columbia Centre for Disease Control and the National Microbiology Laboratory in Winnipeg, Manitoba, using samples from infected patients in Toronto. The map, hailed by WHO as an important step forward in fighting SARS, is being shared with scientists worldwide via the GSC website. See the SARS virus article for more details.

Dr. Donald Low of Mount Sinai Hospital in Toronto described the discovery as having been made with "unprecedented speed." [11] (http://www.cbc.ca/stories/2003/04/12/sars_code030412) A team slaved over the problem 24 hours a day for a mere six days.

As at April 17, 2003 an increase over the previous week in the death rate and especially the increase in deaths in young previously healthy patients has reinforced concerns about the severity of the illness and increased anxiety in cities such as Hong Kong. The reasons for this mortality increase cannot yet be stated with certainty. The following factors may be involved:

• Statistical clustering: It may be in part coincidence that a group of younger deaths have occurred over a short period of time. This can only be adequately assessed by detailed statistical analysis of different cohorts (groups) of patients.

• Late presentations: Patients presenting late in the disease would be expected to have a worse outcome. This has been given as an explanation in a number of cases.

• Drug resistance: This has been proposed as a possible explanation by a Professor of virology from Chinese University. There has been a significant debate in the medical community about the effectiveness of ribavirin. It seems unlikely that the effectiveness would change so dramatically in a short time in young patients.

• Variation in the severity of the disease: This is an important possibility. There have been a number of anecdotal reports that the disease is more severe in the cluster of patients from Amoy Gardens[?]. The W.H.O. considers this as a potentially important factor (April 16 Press briefing). One possible explanation for this is that the environmental process involved led to exposure to large amounts of virus. Another suggestion is that a slight change in the coronavirus led to more severe disease in this cluster. Exposure to a larger amount of virus, or a more severe disease could be sufficient to impact even on the young and previously healthy. These hypotheses can be tested by assessing the outcome in this cohort in addition to RNA typing of the virus in order to determine if slight variation is associated with different disease patterns.

• Variation in the level of medical care: This is a possible factor. The first cohort of 138 patients had a mortality rate of 3.6%. This data has been published in The New England Journal of Medicine (http://content.nejm.org/cgi/content/abstract/NEJMoa030685v2 )

- This graphic represents the evolution of the people probably infected, by main countries (Moving Average of 7 days) and the mortality rate for the last 2 weeks.
- People probably infected = Cumulative case - Number of deaths - Number of people discharged.
- Mortality rate = Deaths / (Deaths + Discharged)
- (Source : WHO WEB SITE)

Progress of the outbreak

See Progress of the SARS outbreak.

Action to try to control SARS

WHO set up a network for doctors and researchers dealing with SARS, consisting of a secure web site to study chest x-rays and a teleconference.

Attempts are being made to control further SARS infection through the use of quarantine. Over 1200 are under quarantine in Hong Kong, while in Singapore and Taiwan, 977 and 1147 are quarantined respectively. Canada also put thousands of people under quarantine. [12] (http://asia.news.yahoo.com/030402/3/v3tb) In Singapore, schools were closed for 10 days and in Hong Kong they are closed until April 21 to contain the spread of SARS. [13] (http://www1.moe.edu.sg/press/2003/pr20030326.htm)

On March 27, 2003, the WHO recommended the screening of airline passengers for the symptoms of SARS. [14] (http://www.who.int/csr/sarsarchive/2003_03_27/en/)

In Singapore, prompted by a bunch of 12 home quarantine order breakers, the government has taken quite a few steps to ensure compliance. Now anyone on home quarantine who does not answer the telephone when the officers call their home at random intervals will get an electronic tag affixed to them, similar to the ones used on prisoners who are on home parole. The government is scheduled to amend the Infectious Diseases Act on April 23rd in an urgent meeting of Parliament to enable them to fine offenders without charging them in court and imprison repeat offenders in an isolated area of a prison.

On April 23 the WHO advised against all but essential travel to Toronto, noting that a small number of persons from Toronto appear to have "exported" SARS to other parts of the world. Toronto public health officials noted that only one of the supposedly exported cases had been diagnosed as SARS and that new SARS cases in Toronto were originating only in hospitals. Nevertheless, the WHO advisory was immediately followed by similar advisories by several governments to their citizens. On April 29 WHO announced that the advisory would be withdrawn on April 30.

Also on April 23rd, Singapore instituted thermal imaging scans to screen all passengers departing Singapore from Changi International Airport. It also stepped up screening of travellers at its Woodlands and Tuas checkpoints with Malaysia. Singapore had previously implemented this screening method for incoming passengers from other SARS affected areas but will move to include all travellers into and out of Singapore by mid to late May. [15] (http://straitstimes.asia1.com.sg/topstories/story/0,4386,184981,00?)

In addition, students (and some teachers) in Singapore have been issued with free personal oral digital thermometers. Students have to take their temperatures daily; usually two or three times a day.

Political and economic reaction to SARS

On March 30, the International Ice Hockey Federation[?] canceled the 2003 IIHF Women's World Championship tournament which was to take place in Beijing.

On April 1, a European airline laid off a batch of employees owing to a drop in travellers caused by the September 11 Terrorist Attack and SARS.

Severe customer drop of Chinese cuisine restaurants in Guangdong, Hong Kong and Chinatowns in North America, 90% decrease in some cases. Business has recovered considerably in some cities after promotion campaigns.

Some members of Hong Kong Legislative Council recommended editing the budget for increased spending on medical services.

Hong Kong merchants withdrew from an international jewellery and timepiece exhibition at Zurich. Switzerland officials enforced a full body check of the 1000 Hong Kong participants that would be finished 2 days before the end of the exhibition. The Swiss Ambassador to Hong Kong replied that such a body check would guard against spread via close contact. A merchant union leader alleged probable racial discrimination towards Chinese merchants, as the exhibition committee allowed the merchants to participate in the exhibition but not to promote their own goods. An estimated several hundred million HK dollars in contracts were lost as a result.

Some conferences and conventions scheduled for Toronto have been canceled, and the production of at least one movie has been moved out of the city. On April 22 the Canadian Broadcasting Corporation reported that the hotel occupancy rate in Toronto was only half the normal rate, and that tour operators were reporting large declines in business. It should be noted that as of April 22 all Canadian SARS cases were believed to be directly or indirectly traceable to the originally identified carriers. SARS is not loose in the community at large in Canada, although a few infected persons have broken quarantine and moved among the general population. No new cases have originated outside hospitals for 20 days.

Nonetheless, on April 23 the WHO extended its travel advice urging postponement of non-essential travel to include Toronto. At the time, city officials and business leaders in the city expect a large economic impact as a result, and an official of the Bank of Canada said that it will have an effect on Canada's national economy.

On April 29 WHO announced that its advisory against unnecessary travel to Toronto would be withdrawn on April 30.

SARS and accusations of racial discrimination

Some members of some Chinese ethnic communities in some Canadian cities have expressed concern that SARS might lead or has led to racial discrimination and stereotyping. The media in the US and Canada has reported on this topic extensively, although there is no evidence so far of any major racial backlash. Stereotyping in Canada seems to be of possible carriers rather than of racial groups. See SARS and accusations of racial discrimination for more detail.

External links and references

See Severe acute respiratory syndrome: External links for a complete list.

Mainstream News

• SARS in Singapore (http://www.channelnewsasia.com/sars/index.htm) - Updated frequently by ChannelNewsAsia
• War On SARS (http://straitstimes.asia1.com.sg/sars/) - Updated frequently by The Straits Times
• SARS?? (http://www.zaobao.com/special/pneumonia/pneumonia) - Lianhe Zaobao Chinese SARS news article collage
• Fighting SARS Together (http://www.xinhuanet.com/zhengfu/sars/) - People's Republic of China Xinhua News Agency
• Yahoo! News search (http://dailynews.yahoo.com/fc/Health/Severe_Acute_Respiratory_Syndrome/) - SARS Full Coverage from leading worldwide news organizations

SARS Weblogs

• SARS Watch Org (http://www.sarswatch.org/) - award winning weblog following SARS around the globe -- updated daily since March
• Docbear's daily SARS updates (http://agonist.got.net/cgi-bin/yabb/YaBB.cgi?board=SARS) -- news and analysis written by Canadian doctor

Official Announcements

• Official SARS information (http://www.who.int/csr/sars/en/) from the World Health Organization
• Official SARS information (http://www.cdc.gov/ncidod/sars/) from the United States Centers for Disease Control
• Official SARS information (http://www.info.gov.hk/dh/ap.htm) from the Hong Kong Department of Health
• Official SARS information (http://www.hc-sc.gc.ca/english/protection/warnings/2003/2003_11.htm) from the Canadian Ministry of Health
• Official SARS information (http://www.moh.gov.cn/) from the PRC Ministry of Health
• Official SARS information (http://www.cdc.gov.tw/En/HealthTopic.ASP?Category=40) from the ROC Center for Disease Control
• Singapore Government SARS Website (http://www.sars.gov.sg/) from the Singapore Ministry of Health and Ministry of Information and the Arts

Medical Mailing Lists

• EMED-L mailing list (http://www.ucsf.edu/its/listserv/emed-l/) - contains "breaking news" discussion of SARS
• CCM-L mailing list (http://www.pitt.edu/~crippen/) - contains "breaking news" discussion of SARS, notably including the dispatches of the intensive-care specialist Tom Buckley on his work on the ongoing Hong Kong outbreak of SARS