Severe Acute Respiratory Syndrome (SARS) is an atypical form of pneumonia that first appeared in November 2002 in Guangdong Province, China.
After the People's Republic of China suppressed all news of the outbreak both internally and abroad, it spread rapidly, reaching neighboring Hong Kong and Vietnam in late February 2003, and then to other countries via international travel of infected persons. The last case in this outbreak occurred in June, 2003. In the outbreak, SARS caused 8,069 cases of disease and 775 deaths.
SARS is fatal in about 10% of cases (see below for more information on mortality rates).
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. The PRC has since officially apologized for early slowness in dealing with the SARS epidemic.
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 ageing 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.
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, Sngapore, Hanoi, Taiwan, and the mainland 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 disease spread in Hong Kong from a mainland doctor on the 9th floor of Metropole Hotel in Kowloon Peninsula, infecting 16 of the hotel visitors. Those visitors traveled to Singapore and Toronto, spreading SARS to those locations.
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. 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.
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 Celsius. 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 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.
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.
With the identification and sequencing of the DNA of the coronvirus 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.
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].
A suspected case of SARS is a patient who has any of the symptoms including a fever of 38 degrees Celsius 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 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).
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, 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.
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.
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. 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. 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.
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.