Laboratory tests for SARS: powerful or peripheral?

To this end, the case definition of SARS has recently been updated, in part to help distinguish the illness caused by SARS-CoV from atypical pneumonia caused by other pathogens.2 Molecular diagnostic tests, such as reverse-transcriptase polymerase chain reaction (RT-PCR), amplify minute quantities of viral RNA and thus may help to detect SARS-CoV early in the course of illness. Molecular tests may also be useful in clinical and epidemiological investigations of clusters of infected patients. However, at present, neither negative results nor single positive results of molecular tests can be considered conclusive for the detection of SARS-CoV. In Tang and colleagues' study, even after repeat testing with RT-PCR, only 54% of the patients for whom diagnostic test results were available had a positive result. In addition, as pointed out by the authors, the presence of other pathogens, such as Mycoplasma pneumoniae and Chlamydia pneumoniae, does not exclude the possibility of coinfection with SARS-CoV. The role that these and other pathogens, such as human metapneumovirus, may play in SARS still needs to be determined. As with all serologic tests available to identify infectious diseases, those used to detect SARS-CoV antibodies are primarily useful retrospectively because the antibodies reach detectable levels later in infection. The first generation of serologic tests appear to give consistent results for samples from patients in Toronto and elsewhere, and they now provide a powerful tool to identify or confirm SARS cases retrospectively. In the series reported by Tang and colleagues, convalescent serum samples were positive in 96% of the patients from whom paired samples were collected. Thus, the current serologic tests may be a good "gold standard" for new or improved diagnostic tests to detect SARS-CoV early in the course of illness in a largely seronegative population. Poon and colleagues5 recently developed a second-generation RT-PCR assay capable of detecting SARS-CoV in up to 88% of respiratory tract samples obtained within the first 3 days after illness onset in confirmed SARS cases in the Hong Kong outbreak. In addition, they showed that the viral load is unusually low early in the course of SARS, as compared with the viral load in other respiratory illnesses. This provides a plausible explanation for the poor detection of SARS-CoV in early samples using the first-generation RT-PCR assays.