Diseases

SARS

SARS is a dangerous viral infection of the respiratory system. At present, there are no medicines to treat it, but pharmaceutical research has identified promising opportunities for new medicines and vaccines.

What is SARS? Top

Severe Acute Respiratory Syndrome (SARS) is a viral respiratory illness caused by a corona virus. Corona viruses are a group of viruses that have a crown-like appearance (“corona“ is the Latin word for crown) when viewed under the electron microscope. Several species of corona virus have been known to be a common cause of mild to moderate upper-respiratory illness in humans. They also cause respiratory, gastrointestinal, liver and neurological disease in animals.

The time between exposure to the virus and the onset of symptoms of the disease, i.e. the incubation period, is typically two to seven days. In general, SARS begins with a high fever over 39°C. Other symptoms may include headache, an overall feeling of discomfort, and body aches. Some patients show mild respiratory symptoms at the outset. About 10-20 per cent of patients have diarrhoea. After another period of two to seven days, SARS patients develop a dry cough. Most patients develop severe pneumonia and need to be hospitalised.

The main way that SARS spreads is by close person-to-person contact. The corona virus is thought to be transmitted by respiratory droplets produced when an infected person coughs or sneezes. Droplet spread can happen when droplets are propelled at short distance, generally up to one metre. Corona virus has also been found in the sweat, urine and stools of SARS patients. The agent may be spread when a person touches contaminated material. In the context of SARS, close contact means having cared for or lived with someone with SARS or having direct contact with respiratory secretions or body fluids of a patient with SARS. Patients are most likely to be contagious when they have symptoms, such as fever or cough, with a peak of contagiousness during the second week of illness.

In summarising their experiences during the SARS outbreaks in Canada and Taiwan, epidemiologists noted that certain people were very efficient at transmitting corona virus and that so-called “super-spreaders“ played a crucial role in the epidemic. The causes of these super-spreading events are unclear. Possible explanations include specific host characteristics, e.g. co-infection with other respiratory viruses, higher level of virus shedding, or environmental factors.

Since its first outbreak in late 2002, research groups have been extremely busy in trying to identify the crucial features of the disease, including the natural reservoir of the pathogen causing it, its virulence, and the pathways of infection. In October 2004, attempts to identify the wildlife hosts of SARS lead to the conclusion that civet cats which had been suspected of carrying the agent were not the natural host of the virus. Twelve months later, scientists who had focused their research on the habitats of wild bats reported that antibody research found several genetically diverse corona viruses, one of which closely resembles the SARS corona virus. These findings implicate bats in China as the wild reservoir of the agent that causes SARS.

Who does SARS affect? Top

According to the World Health Organisation (WHO), a total of some 8,000 people worldwide fell ill with SARS during the 2002/2003 outbreak. Of these, ca. 800 patients died, meaning that SARS has a fatality rate of ten per cent. After SARS had been reported in Asia in February 2003, the illness spread to more than two dozen countries in North America, South America, Europe, and Asia over the next few months before the global outbreak could be contained. In 2004, there was another small outbreak of the disease among staff at a virology institute in China.

Most SARS cases reported so far occurred in previously healthy adults between 25 to 70 years of age, and few SARS cases have been reported in children below 15 years of age. There does not seem to be gender specificity. Minor gender differences in SARS incidence can be explained by differences in exposure, especially given the gender ratio in hospital healthcare providers.

 

 

Electron-microscopic photo of the corona virus causing SARS

Summary (abridged) of probable SARS cases with onset of illness from 1 November 2002 to 31 July 2003

Cumulative number of cases
Areas Total

Number
of deathsª

China 7429

648

France 7

1

Germany 9

0

Italy 4

0

Ireland 1

0

Romania 1

0

Russian Federation 1

0

Singapore 238

33

Spain 1 0
Sweden 5 0
Switzerland 1 0
United Kingdom 4 0
United States 27 0

a. Includes only cases whose death is attributed to SARS.

Present treatments Top

At present, the most effective treatment for SARS is unknown. There exists no specific medicine to treat the infection. Treatment regimens have included a variety of antibiotics designed to treat bacterial agents of atypical pneumonia. Some therapies have included antiviral agents. Steroids have also been given to patients in combination with virustatics.

Patients with SARS receive the same treatment that would be used for a case with any serious community-acquired atypical pneumonia, including mechanical ventilation and critical care. Individuals with confirmed or suspected infection should be hospitalised under isolation.

What’s in the development pipeline? Top

A phase 1 dose-ranging study of low dose oral interferon-alpha which is derived from human white blood cells is underway.

Continuing work on a vaccine against SARS is still vital, because of the risk of it re-emerging either from its original animal reservoirs or through laboratory contamination. One research group has developed a potential SARS vaccine. The product is a subunit vaccine, based on the viral S-protein, which is produced in a particular expression vector system. Another approach towards a potential SARS vaccine candidate is a DNA vaccine, which encodes the spike (S) glycoprotein of the SARS-associated corona virus. The vaccine has been shown to induce T cell and neutralising antibody responses, as well as protective immunity in an animal model. Manufacturing of a highly purified vaccine suitable for clinical trials is underway and testing in humans is planned for 2006.

The quest for a vaccine could be helped by new research into how different people respond to infection. Apparently, severity of infection depends on a patient’s late stage immune response. Patients with less severe infection showed a strong initial immune response, while those who went on to experience life-threatening SARS later failed to express transcription factors that were turned on in patients with mild infection. It is not yet known what determines this difference; it could be linked to previous viral exposure.

In September 2005, scientists reported that attachment of the SARS corona virus to human tissue takes place through a spike protein on the viral surface that binds to a cell-surface peptidase domain of angiotensin-converting enzyme (ACE). The researchers were able to determine the structure of the binding domain bound to the domain of human ACE. The details of the interface suggest how a few residue changes led to efficient cross-species infection and human-to-human transmission in the 2002 and 2003 SARS outbreaks. The structure will guide design of receptor-binding domain variants in the development of further options towards an effective SARS vaccine.

Researchers also hope to have developed a viable pathogenicity model for SARS by 2006, and to have live and attenuated vaccines ready for testing.