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Published at www.nejm.org April 10, 2003 (10.1056/NEJMoa030781)

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ABSTRACT

Background A worldwide outbreak of severe acute respiratory syndrome (SARS) has been associated with exposures originating from a single ill health care worker from Guangdong Province, China. We conducted studies to identify the etiologic agent of this outbreak.

Methods We received clinical specimens from patients in six countries and tested them, using virus isolation techniques, electron-microscopical and histologic studies, and molecular and serologic assays, in an attempt to identify a wide range of potential pathogens.

Results No classic respiratory or bacterial respiratory pathogen was consistently identified. However, a novel coronavirus was isolated from patients who met the case definition of SARS. Cytopathological features were noted microscopically in Vero E6 cells inoculated with a throat-swab specimen. Electron-microscopical examination of cultures revealed ultrastructural features characteristic of coronaviruses. Immunohistochemical and immunofluorescence staining revealed reactivity with group I coronavirus polyclonal antibodies. Consensus coronavirus primers designed to amplify a fragment of the polymerase gene by reverse transcription-polymerase chain reaction (RT-PCR) were used to obtain a sequence that clearly identified the isolate as a unique coronavirus only distantly related to previously sequenced coronaviruses. With specific diagnostic RT-PCR primers we identified several identical nucleotide sequences in 12 patients from several locations, a finding consistent with a point source outbreak. Indirect fluorescent antibody tests and enzyme-linked immunosorbent assays made with the new coronavirus isolate have been used to demonstrate a virus-specific serologic response. Preliminary studies suggest that this virus may never before have infected the U.S. population.

Conclusions A novel coronavirus is associated with this outbreak, and the evidence indicates that this virus has an etiologic role in SARS. The name Urbani SARS-associated coronavirus is proposed for the virus.

Notice: Because of possible public health implications, this article was published at www.nejm.org on April 10, 2003. It will appear in the May 15 issue of the Journal.

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