Interpretation of diagnostic laboratory tests for severe acute respiratory syndrome: the Toronto experience

Abstract

Background: An outbreak of severe acute respiratory syndrome (SARS) began in Canada in February 2003. The initial diagnosis of SARS was based on clinical and epidemiological criteria. During the outbreak, molecular and serologic tests for the SARS-associated coronavirus (SARS-CoV) became available. However, without a "gold standard," it was impossible to determine the usefulness of these tests. We describe how these tests were used during the first phase of the SARS outbreak in Toronto and offer some recommendations that may be useful if SARS returns.

Methods: We examined the results of all diagnostic laboratory tests used in 117 patients admitted to hospitals in Toronto who met the Health Canada criteria for suspect or probable SARS. Focusing on tests for SARS-CoV, we attempted to determine the optimal specimen types and timing of specimen collection.

Results: Diagnostic test results for SARS-CoV were available for 110 of the 117 patients. SARS-CoV was detected by means of reverse-transcriptase polymerase chain reaction (RT-PCR) in at least one specimen in 59 (54.1%) of 109 patients. Serologic test results of convalescent samples were positive in 50 (96.2%) of 52 patients for whom paired serum samples were collected during the acute and convalescent phases of the illness. Of the 110 patients, 78 (70.9%) had specimens that tested positive by means of RT-PCR, serologic testing or both methods. The proportion of RT-PCR test results that were positive was similar between patients who met the criteria for suspect SARS (50.8%, 95% confidence interval [CI] 38.4%-63.2%) and those who met the criteria for probable SARS (58.0%, 95% CI 44.2%-70.7%). SARS-CoV was detected in nasopharyngeal swabs in 33 (32.4%) of 102 patients, in stool specimens in 19 (63.3%) of 30 patients, and in specimens from the lower respiratory tract in 10 (58.8%) of 17 patients.

Interpretation: These findings suggest that the rapid diagnostic tests in use at the time of the initial outbreak lack sufficient sensitivity to be used clinically to rule out SARS. As tests for SARS-CoV continue to be optimized, evaluation of the clinical presentation and elucidation of a contact history must remain the cornerstone of SARS diagnosis. In patients with SARS, specimens taken from the lower respiratory tract and stool samples test positive by means of RT-PCR more often than do samples taken from other areas.

Fig. 1: Diagnostic testing for severe acute respiratory syndrome coronavirus (SARS-CoV) in patients admitted to hospital in Toronto who met the Health Canada criteria for suspect or probable SARS. A total of 110 patients had specimens tested by means of reverse-transcriptase polymerase chain reaction (RT-PCR) (n = 109) or serologic testing (n = 107). Of the specimens tested by RT-PCR, 59 (54.1%) were positive. Of the 110 patients whose specimens underwent RT-PCR or serologic testing, 78 (70.9%) had specimens that tested positive by one or both methods. A similar proportion of suspect and probable cases had positive RT-PCR results (50.8% and 58.0% respectively). Of the 52 patients with paired serum samples, 50 (96.2%) were seropositive against SARS-CoV; 32 (64.0%) of these 50 patients also had positive RT-PCR results.

Fig. 2: Proportion of patients with RT-PCR results positive for SARS-CoV, by day of illness. The results are shown for all specimen types. Error bars represent 95% confidence intervals.

Fig. 3: Proportion of patients with serologic test results positive for SARS-CoV antibodies, by day of illness. Error bars represent 95% confidence intervals.