The reverse transcription (RT)-PCR protocols of two
World Health Organization (WHO) severe acute respiratory syndrome (SARS) network laboratories (WHO SARS network laboratories at The University of Hong Kong [WHO-HKU]
and at
the Bernhard-Nocht Institute in Hamburg, Germany [WHO-Hamburg])
were evaluated for rapid diagnosis of a novel coronavirus (CoV) associated with SARS in
J.S. Malik Peiris, Larry J. Anderson, Christian Drosten, leaders of research teams at the University of Hong Kong, U.S. CDC’s Respiratory and Enteric Viruses Branch, Atlanta, and Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany,
respectively, have identified a new type of coronavirus as the etiological agent for severe acute respiratory syndrome (SARS). Announced on March 21, 2003, their research reports were published online in The Lancet on April 8 (Peiris) and
New England Journal of Medicine on April 10, 2003 (Anderson and Drosten).
Their labs are part of a broader global network (of 13 labs) coordinated by the German-born virologist Klaus Stohr, project leader of Global Influenza Program at The WHO in Geneva. The network participants exchange clinical specimens, research data, and ideas on a daily basis. Participants described that the level of collaboration was unprecedented and “historic” given that scientific discoveries are usually very competitive in nature. Their collaborative and ultimately credit-sharing spirit has made the discovery of an etiological agent of a new disease one of the fastest in history.
The identification of a novel coronavirus as the cause for SARS was based on three primary lines of evidence.
First, serum antibodies recovered from SARS patients that are cross-reactive to coronavirus antigens suppressed the growth of agents contained in SARS samples.
Second, coronavirus-like particles with distinctive spikes are seen in SARS specimens by electron microscopy.
Third, a short stretch of genome sequence of the SARS agent is related to, but quite different from, the known coronaviruses uated by RT- PCR.
BACKGROUND: The worldwide outbreak of severe acute respiratory syndrome (SARS) is associated with a newly discovered coronavirus, SARS-associated coronavirus (SARS-CoV). We did clinical and experimental studies to assess the role of this virus in the cause of SARS. METHODS: We tested clinical and postmortem samples from 436 SARS patients in six countries for infection with SARS-CoV, human metapneumovirus, and other respiratory pathogens. We infected four cynomolgus macaques (Macaca fascicularis) with SARS-CoV in an attempt to replicate SARS and did necropsies on day 6 after infection. FINDINGS: SARS-CoV infection was diagnosed in 329 (75%) of 436 patients fitting the case definition of SARS; human metapneumovirus was diagnosed in 41 (12%) of 335, and other respiratory pathogens were diagnosed only sporadically. SARS-CoV was, therefore, the most likely causal agent of SARS. The four SARS-CoV-infected macaques excreted SARS-CoV from nose, mouth, and pharynx from 2 days after infection. Three of four macaques developed diffuse alveolar damage, similar to that in SARS patients, and characterised by epithelial necrosis, serosanguineous exudate, formation of hyaline membranes, type 2 pneumocyte hyperplasia, and the presence of syncytia. SARS-CoV was detected in pneumonic areas by virus isolation and RT-PCR, and was localised to alveolar epithelial cells and syncytia by immunohistochemistry and transmission electron microscopy. INTERPRETATION: Replication in SARS-CoV-infected macaques of pneumonia similar to that in human beings with SARS, combined with the high prevalence of SARS-CoV infection in SARS patients, fulfill the criteria required to prove that SARS-CoV is the primary cause of SARS.