Fact sheet for clinicians: interpreting SARS test results

The Health Protection Agency (HPA) National Influenza Reference Laboratory and other laboratories have been working to determine the cause of severe acute respiratory syndrome (SARS). Please review the Information on SARS, including the case definition and infection control guidelines.

SARS coronavirus (SARS CoV) has been demonstrated to be the cause of SARS. The Influenza Reference Laboratory and others have developed new tests for SARS human coronavirus which are currently available for diagnostic use.

Results of these tests are being provided to referring doctors, general practitioners, and health departments that reported SARS cases. The following are some key points and issues that clinicians providing care for patients with SARS may find useful when interpreting coronavirus testing results.

What are coronaviruses?

What evidence is there to suggest that coronaviruses may be linked with SARS?

Is there a proven laboratory test for SARS?

What tests for human coronavirus are being done and which results are being reported?

What does it mean if a patient with SARS has a positive result for coronavirus?

What does it mean if a patient with SARS has a negative coronavirus test result?

What does it mean if the test results are positive for human metapneumovirus?

What other tests are needed for patients with both SARS and a positive human coronavirus test?

Should a patient with SARS who has negative coronavirus test results continue with the isolation precautions?

Has the new information about coronavirus changed the recommendations for medical treatment for patients with SARS?

Should a person who travelled to an area where there is community transmission of SARS or who had contact with a SARS patient be tested even if not ill?

What are coronaviruses?

Coronaviruses are a group of viruses that have a halo or crown-like (corona) appearance when viewed under a microscope. These viruses are a common cause of mild to moderate upper-respiratory illness in humans and are associated with respiratory, gastrointestinal, liver, and neurological disease in animals. Coronaviruses can survive in the environment for as long as three hours, and there is evidence that the SARS CoV may be able to survive longer than this.

What evidence is there to suggest that coronaviruses may be linked with SARS?

Scientists isolated a virus from patients who had SARS and then used several laboratory methods to characterize the agent. Examination by electron microscopy revealed that the virus had the distinctive shape and appearance of coronaviruses. Tests of serum specimens from patients with SARS showed that the patients appeared to have been infected recently with this coronavirus. Other tests demonstrated that coronavirus was present in a variety of clinical specimens from patients, including nose and throat swab specimens. In addition, genetic analysis suggests that this new virus belongs to the family of coronaviruses but differs from previously identified coronaviruses. The SARS coronavirus has been shown to cause similar pathological features and has been recovered from infected animal models.

Is there a proven laboratory test for SARS?

Although no test for SARS is widely available yet in the UK or Europe, the reference laboratory has developed and is using several tests to identify the SARS virus. Current tests detect RNA and antibodies to the new coronavirus. SARS will continue to be diagnosed on the basis of symptoms and exposures, as described in the current SARS case definition, positive serology test results are incorporated in the case definition.

What tests for human coronavirus are being done and which results are being reported?

At this time, tests for the new human coronavirus are still being refined, and no sensitivity or specificity data are available. Reverse transcription-polymerase chain reaction (RT-PCR) detects virus early in respiratory specimens, peak detection is between six and ten days (samples may be positive between day 0 and 18). Virus can be detected in faecal samples between days five and 28. It should be noted that virus detection by PCR does not necessarily mean that viable virus is present. Virus culture is used for detection early during the illness.

Several types of newly developed tests are currently being used at the influenza reference laboratory to test for coronavirus:

1. Two reverse transcription-polymerase chain reaction (RT-PCR) tests are available. These can detect corona virus RNA in clinical specimens, including serum, stool, and nasal secretions. One is non-specific and detects any member of the Coronavirus family, the other is specific for the SARS CoV Viral isolation for SARS CoV has also been done. In these studies, clinical specimens from SARS patients are co-cultured with well-characterized cell lines, laboratories then look for evidence of corona virus replication in these cultured cells.
2. Serum antibody tests, including indirect and enzyme immunoassay (EIA) have been developed. The ELISA test is currently used at the reference laboratory to assess serological evidence of infection.

Some people, however, do not test antibody positive until more than 20 days after illness onset. For patients with a negative antibody test result whose specimens were obtained less that 20 days after illness onset, an additional antibody test should be done on a specimen taken more than 20 days after onset to determine if they are negative or positive for corona virus. A result from a convalescent serum sample will only be considered reliable if taken approximately three to four weeks after the onset of illness.

What does it mean if a patient with SARS has a positive result for coronavirus?

A positive result with the non-specific coronavirus PCR implies that any virus within the Coronavirus family is present. This results does not necessarily mean that the SARS CoV is present. A positive result from the specific SARS CoV PCR means that the patient with SARS also has or recently had an infection with the new SARS CoV. Other viruses or combinations of viruses might also contribute to the illness and the reference laboratory tests a range of respiratory pathogens. Please note that all corona virus detections by PCR are confirmed by sequence analysis.

What does it mean if a patient with SARS has a negative coronavirus test result?

Some patients with SARS may have negative test results for SARS CoV. At this time, however, it is still considered that these individuals are SARS patients on the basis of symptoms and exposures, not on laboratory test results. This interpretation may change as the tests improve. There are several possibilities to explain negative test results in a patient with SARS.

1. The patient did not have an infection with this new coronavirus. Other viruses or infectious agents may also contribute to SARS or illnesses like SARS. It can sometimes be difficult to find out which germ (virus, bacteria, etc) is causing a person to be ill with fever, respiratory symptoms, and pneumonia. For example, only about half of the cases of pneumonia that are diagnosed have a specific etiologic agent detected.
2. The tests may be incorrect ("false-negative"). Results from more sensitive, improved tests might have been positive.
   The samples were not obtained at a time point in the course of SARS CoV infection when test results are positive. The RT-PCR test will only be positive if there is viral RNA in the specimen. This may be for a fairly brief period, depending on which specimen (eg serum, stool, nasal secretions) was tested. The antibody tests may not become positive until more than 21 days after illness onset.

What does it mean if the test results are positive for human metapneumovirus?

Specimens from SARS patients have tested positive for other viruses, including human metapneumovirus. Human metapneumovirus is a recently recognized virus that belongs to the Paramyxovirus family of viruses, which cause a broad range of respiratory and childhood illnesses, including mumps, measles, and croup. Human metapneumovirus is genetically related to respiratory syncytial virus, which is a common cause of lower respiratory tract infection in children. Several laboratories have reported positive test results for human metapneumovirus in patients with SARS. There is not enough information to determine what role, if any, human metapneumovirus might have in causing SARS.

What other tests are needed for patients with both SARS and a positive human coronavirus test?

To help scientists understand more about the relationship between coronavirus infection and SARS, we are asking SARS patients with a positive human coronavirus test to participate in additional investigations, including more testing of clinical specimens. Participation is voluntary.

Should a patient with SARS who has negative coronavirus test results continue with the isolation precautions?

Yes. SARS patients with negative test results still have the clinical diagnosis of SARS and should adhere to isolation precautions recommended for all patients with SARS. All SARS patients should limit interactions outside the home and should not go to work, school, out-of-home childcare, or other public areas until seven days after resolution of fever and respiratory symptoms. During this time, the infection control precautions described by the HPA should be followed.

Has the new information about coronavirus changed the recommendations for medical treatment for patients with SARS?

The possibility that a new coronavirus is the cause of SARS has not changed treatment recommendations. The new coronavirus is being tested against various antiviral drugs to see if an effective treatment can be found.

Should a person who travelled to an area where there is community transmission of SARS or who had contact with a SARS patient be tested even if not ill?

See case definition  regarding community transmission.

People who have potentially been exposed to SARS patients should not be tested unless the HPA or their health department specifically asks them to be part of one of the ongoing SARS investigations. We do not know yet how to interpret the results of testing in persons who are not ill.

What other investigations related to SARS are planned?

The CDSC or HPA may contact some SARS patients regardless of whether the coronavirus test was positive or negative. These patients might be asked to participate in investigations that are trying to understand more about coronavirus and SARS and how they are related to each other. If a patient agrees to take part in those investigations, his or her permission would be requested to collect more specimens for testing.

Specimens should be sent to the HPA National Influenza Reference Laboratory at Colindale.
The number of tests that can be done is limited by the amount and type of specimens and the test type. Molecular detection in respiratory secretions is prioritized if there is a limited sample volume.

Investigation of cases can be discussed with Dr Maria Zambon or Dr Paul Simons (virology) via the SRM or CDSC duty doctor if required.

Last reviewed: 27 February 2009