The aetiology, origins, and diagnosis of severe acute respiratory syndrome

Abstract

Severe acute respiratory syndrome (SARS) is a new infectious disease that first emerged in Guangdong province, China, in November, 2002. A novel coronavirus was later identified in patients with SARS. The detection of the virus in these patients, its absence in healthy controls or other patients with atypical pneumonia, and the reproduction of a similar disease in a relevant animal model fulfilled Koch's postulates for implicating this coronavirus as the causal agent of SARS. The full genome sequence was determined within weeks of the virus's identification. The rapid progress in the aetiology, the development of laboratory diagnostic tests, and the defining of routes of viral transmission were facilitated through a unique WHO-coordinated virtual network of laboratories, which shared information on a real-time basis through daily teleconferences. Subsequent studies have indicated that the SARS coronavirus is of animal origin, that its precursor is still present in animal populations within the region, and that live-animal markets in southern China may have provided the animal-human interphase that allowed this precursor virus to adapt to human-human transmission. These findings underscore the potential for the re-emergence of SARS and the need for laboratory tests for early diagnosis. However, the low viral load in the respiratory tract makes early diagnosis of SARS a diagnostic challenge, although improvements in the sensitivity of molecular diagnostic methods continue to be made.

Figure 1

Thin section electron micrograph of the surface of an infected FRhK4 cell showing SARS coronavirus with spikes. Bar=100 nm.

Figure 2

Investigation of the animal precursor of the SARS coronavirus in a live-animal market in China.

Figure 3

Phylogeny of human and animal SARS coronaviruses isolated in 2003. The scale bar represents the genetic distance estimated by Kimura's two parameter substitution model (adapted from reference 41, with permission).

Figure 4

Genetic organisation of SARS coronavirus-like viruses found in human beings and animals (modified from reference 41). Open reading frames (ORFs) 1a and 1b, encoding the non-structural polyproteins, and those encoding the spike (S), envelope (E), membrane (M), and nucleocapsid (N) structural proteins are indicated (green boxes). ORFs for putative proteins 7a, 8a, 8b and 9b are indicated by brown boxes. An extra 29-nucleotide sequence is ORF8 of the animal SARS coronavirus (based on AY278554 numbering). The presence of this 29-nucleotide sequence in animal isolates generates a new protein-encoding sequence in ORF8 (blue box). The labelling system is based on reference 37.