SARS REVIEWSevere acute respiratory syndrome (SARS) is a serious form of pneumonia. It is caused by a virus that was first identified in 2003. Infection with the SARS virus causes acute respiratory distress (severe breathing difficulty) and sometimes death.SARS is a dramatic example of how quickly world travel can spread a disease. It is also an example of how quickly a connected health system can respond to a new health threat.

Background Information:

World Health Organization (WHO) physician Dr. Carlo Urbani identified SARS as a new disease in 2003. He diagnosed it in a 48-year-old businessman who had traveled from the Guangdong province of China, through Hong Kong, to Hanoi, Vietnam. The businessman and the doctor who first diagnosed SARS both died from the illness.

In the meantime, SARS was spreading. Quickly it infected thousands of people around the world, including people in Asia, Australia, Europe, Africa, and North and South America. Schools closed throughout Hong Kong and Singapore. National economies were affected.The WHO identified SARS as a global health threat, and issued a travel advisory. WHO updates closely tracked the spread of SARS. It wasn't clear whether SARS would become a global pandemic.The fast global public health response helped to stem the spread of the virus. By June 2003, the number of new cases was down enough that on June 7, the WHO stopped its daily reports. But even though the number of new cases dwindled and travel advisories began to be lifted, every new case had the potential to spark another outbreak.SARS appears to be here to stay. It has changed the way that the world responds to infectious diseases during a time of widespread international travel. The 2003 outbreak had an estimated 8,000 cases and 750 deaths. Deaths occurred mainly in older patients.

Causes, incidence, and risk factors

SARS is caused by a member of the coronavirus family of viruses (the same family that can cause the common cold). It is believed the 2003 epidemic started when the virus spread from small mammals in China.When someone with SARS coughs or sneezes, infected droplets spray into the air. You can catch the SARS virus if you breathe in or touch these particles. The SARS virus may live on hands, tissues, and other surfaces for up to 6 hours in these droplets and up to 3 hours after the droplets have dried.While the spread of droplets through close contact caused most of the early SARS cases, SARS might also spread by hands and other objects the droplets has touched. Airborne transmission is a real possibility in some cases. Live virus has even been found in the stool of people with SARS, where it has been shown to live for up to 4 days. The virus may be able to live for months or years when the temperature is below freezing.With other coronaviruses, becoming infected and then getting sick again (re-infection) is common. This may also be the case with SARS.Symptoms usually occur about 2 to 10 days after coming in contact with the virus. There have been some cases where the illness started sooner or later after first contact. People with active symptoms of illness are contagious, but it is not known for how long a person may be contagious before or after symptoms appear.

Symptoms

The hallmark symptoms are:1. Cough2. Difficulty breathing3. Fever greater than 100.4 degrees F (38.0 degrees C)4. Other breathing symptoms

The most common symptoms are:1. Chills and shaking2. Cough -- usually starts 2-3 days after other symptoms3. Fever4. Headache5. Muscle aches

Less common symptoms include:

1. Cough that produces phlegm (sputum)2. Diarrhea3. Dizziness4. Nausea and vomiting5. Runny nose6. Sore throat

In some people, the lung symptoms get worse during the second week of illness, even after the fever has stopped.

Signs and tests

Your health care provider may hear abnormal lung sounds while listening to your chest with a stethoscope. In most people with SARS, changes on a chest x-ray or chest CT show pneumonia, which is typical with SARS.

Tests used to diagnose SARS might include:1. Arterial blood tests2. Blood clotting tests3. Blood chemistry tests4. Chest x-ray or chest CT scan5. Complete blood count (CBC)

Tests used to quickly identify the virus that causes SARS include:

1. Antibody tests for SARS2. Direct isolation of the SARS virus3. Rapid polymerase chain reaction (PCR) test for SARS virus

All current tests have some limitations. They may not be able to easily identify a SARS case during the first week of the illness, when it is most important.

TreatmentPeople who are thought to have SARS should be checked right away by a health care provider. If they are suspected of having SARS, they should be kept isolated in the hospital.

Treatment may include:

1. Antibiotics to treat bacteria that cause pneumonia2. Antiviral medications (although how well they work for SARS is unknown)3. High doses of steroids to reduce swelling in the lungs4. Oxygen, breathing support (mechanical ventilation), or chest therapy

In some serious cases, the liquid part of blood from people who have already recovered from SARS has been given as a treatment.

There is no strong evidence that these treatments work well. There is evidence that the antiviral medication, ribavirin, does not work.

Expectations (prognosis)The death rate from SARS was 9 to 12% of those diagnosed. In people over age 65, the death rate was higher than 50%. The illness was milder in younger patients.Many more people became sick enough to need breathing assistance. And even more people had to go to hospital intensive care units.Public health policies have been effective at controlling outbreaks. Many nations have stopped the epidemic in their own countries. All countries must continue to be careful to keep this disease under control. Viruses in the coronavirus family are known for their ability to change (mutate) in order to spread among humans.

Complications Respiratory failure Liver failure Heart failure

Prevention

Reducing your contact with people who have SARS lowers your risk for the disease. Avoid travel to places where there is an uncontrolled SARS outbreak. When possible, avoid direct contact with persons who have SARS until at least 10 days after their fever and other symptoms are gone.

1. Hand hygiene is the most important part of SARS prevention. Wash your hands or clean them with an alcohol-based instant hand sanitizer.

2. Cover your mouth and nose when you sneeze or cough. Droplets that are released when a person sneezes or coughs are infectious.

3. Do not share food, drink, or utensils.4. Clean commonly touched surfaces with an EPA-approved disinfectant.5. In some situations, masks and goggles may be useful for preventing the spread of the disease. You may

use gloves when handling any items that may have touched infected droplets.

Laboratory test result criteria for confirming or rejecting the diagnosis of SARS remain to be defined.

1. Molecular tests (PCR)

Polymerase chain reaction (PCR) can detect genetic material of the SARS-CoV in various specimens (blood, stool, respiratory secretions or body tissues sampling for Severe Acute Respiratory Syndrome (SARS) diagnostic tests). Primers, which are the key pieces for a PCR test, have been made publicly available by WHO network laboratories on the WHO web site. A ready-to-use PCR test kit containing primers and positive and negative control has been developed. Testing of the kit by network members is expected to quickly yield the data needed to assess the test’s performance, in comparison with primers developed by other WHO network laboratories and in correlation with clinical and epidemiological data.

Principally, existing PCR tests are very specific but lack sensitivity. This means that negative tests cannot rule out the presence of the SARS virus in patients. Furthermore, contamination of samples in laboratories in the absence of laboratory quality control can lead to false positive results.

Positive PCR results, with the necessary quality control procedures in place. Recommendations for laboratories testing for SARS-coronavirus, are very specific and mean that there is genetic material (RNA) of the SARS-CoV in the sample. This does not mean that there is live virus present, or that it is present in a quantity large enough to infect another person.

Negative PCR results do not exclude SARS. SARS-CoV PCR can be negative for the following reasons: - The patient is not infected with the SARS coronavirus; the illness is due to another infectious agent (virus, bacterium, fungus) or a non-infectious cause. - The test results are incorrect (“false-negative”). Current tests need to be further developed to improve sensitivity. - Specimens were not collected at a time when the virus or its genetic material was present. The virus and its genetic material may be present for a brief period only, depending on the type of specimen tested.

2. Antibody tests

These tests detect antibodies produced in response to the SARS coronavirus infection. Different types of antibodies (IgM and IgG) appear and change in level during the course of infection. They can be undetectable at the early stage of infection. IgG usually remains detectable after resolution of the illness.

The following test formats are being developed, but are not commercially available yet: - ELISA (Enzyme Linked ImmunoSorbant Assay): a test detecting a mixture of IgM and IgG antibodies in the serum of SARS patients yields positive results reliably at around day 21 after the onset of illness.– IFA (Immunofluorescence Assay): a test detecting IgM antibodies in serum of SARS patients yields positive results after about day 10 of illness. This test format is also used to test for IgG. This is a reliable test requiring the use of fixed SARS virus on an immunofluorescence microscope.

Positive antibody test results indicate a previous infection with SARS-CoV. Seroconversion from negative to positive or a four-fold rise in antibody titre from acute to convalescent serum indicates recent infection.

Negative antibody test results: No detection of antibody after 21 days from onset of illness seems to indicate that no infection with SARS-CoV took place.

3. Cell culture

Virus in specimens (such as respiratory secretions, blood or stool) from SARS patients can also be detected by inoculating cell cultures and growing the virus. Once isolated, the virus must be identified as the SARS virus with further tests. Cell culture is a very demanding test, but currently (with the exception of animal trials) only means to show the existence of a live virus.

Positive cell culture results indicate the presence of live SARS-CoV in the sample tested.

Negative cell culture results do not exclude SARS (see negative PCR test result).