The Cause Of Severe Acute Respiratory Syndrome: What Did We Learn From It?

Severe acute respiratory syndrome (SARS) was the first major global public health crisis of the 21st century. In March 2003, we reported to the World Health Organization (WHO) the discovery of a novel coronavirus (CoV) responsible for this newly emerged disease. SARS first emerged in Guangdong, China in November 2002, leading to major outbreaks in the Provincial capital Guangzhou in January. We first heard about these outbreaks in mid-February 2003. Hong Kong set up enhanced surveillance for all patients with severe pneumonia of unknown aetiology in Hong Kong, especially those with a travel history to Guangdong. Our investigation for known respiratory pathogens proved negative. We then started to look more broadly for unusual viruses, including attempting virus culture using a range of cell lines not normally used for respiratory viruses, broad-range PCR/RT-PCR, random primer RT-PCR methods as well as electron microscopy of a lung biopsy from a suspected patient. By March 17, 2003, we began to see subtle changes in FRhk 4 monkey kidney cells inoculated with specimens from two suspected patients. By electron microscopy, we could see virus particles within these cells and we then used fixed infected cells to demonstrate antibody responses in paired sera from a number of suspected SARS patients but not in controls. Using random RT-PCR, we were able to identify the virus as a novel coronavirus. The initial short RNA sequence of 646 nucleotides obtained from the random RT-PCR rapidly allowed the development of RT-PCR assays for detecting SARS patients (1). All these findings were shared in real-time via daily teleconferences organized by the WHO to link up laboratories working on this outbreak. Two other laboratories within the network (Centers for Disease Control and Prevention, USA and Bernhard Nocht Institute for Tropical Medicine, Hamburg) reported similar findings from other SARS patients but others were still arguing for other aetiologies (e.g., human metapneumovirus). Sharing of data within the WHO network allowed a rapid consensus that the novel coronavirus was indeed the cause of SARS.