Epidemiology and cause of severe acute respiratory syndrome (SARS) in Guangdong, People's Republic of China, in February, 2003

Abstract

Background: An epidemic of severe acute respiratory syndrome (SARS) has been associated with an outbreak of atypical pneumonia originating in Guangdong Province, People's Republic of China. We aimed to identify the causative agent in the Guangdong outbreak and describe the emergence and spread of the disease within the province.

Methods: We analysed epidemiological information and collected serum and nasopharyngeal aspirates from patients with SARS in Guangdong in mid-February, 2003. We did virus isolation, serological tests, and molecular assays to identify the causative agent.

Findings: SARS had been circulating in other cities of Guangdong Province for about 2 months before causing a major outbreak in Guangzhou, the province's capital. A novel coronavirus, SARS coronavirus (CoV), was isolated from specimens from three patients with SARS. Viral antigens were also directly detected in nasopharyngeal aspirates from these patients. 48 of 55 (87%) patients had antibodies to SARS CoV in their convalescent sera. Genetic analysis showed that the SARS CoV isolates from Guangzhou shared the same origin with those in other countries, and had a phylogenetic pathway that matched the spread of SARS to the other parts of the world.

Interpretation: SARS CoV is the infectious agent responsible for the epidemic outbreak of SARS in Guangdong. The virus isolated from patients in Guangdong is the prototype of the SARS CoV in other regions and countries.

Figure 1

SARS outbreaks in Guangdong Province, People's Republic of China The geographic distribution of SARS outbreak in Guangdong Nov 16, 2002, to Feb 9, 2003. Number of cases are shown in brackets. Approximate dates of the onset of the outbreaks for each city were Foshan, Nov 16, 2002; Heyuan, Dec 17, 2002; Zhongshan, Dec 26, 2003; Guangzhou, Jan 31, 2003; Jiangmen, Jan 10, 2003; Shenzhen, Jan 15, 2003.

Figure 2

The outbreak of SARS in Zhongshan, People's Republic of China 28 cases were reported from Dec 26, 2002 to Jan 19, 2003. 13 were health-care workers.

Figure 3

Immunofluorescent identification of coronavirus-infected cells in nasopharyngeal samples Arrows show respiratory epithelia cells: bronchial columnar cells (A) and squamous cells (B), which were reactive with the convalescent serum, but not with the acute serum (C and D) (×400). Paired sera used in the immunofluorescent tests were obtained from a patient with confirmed coronavirus infection. Titre of coronavirus-specific antibodies was 1:1280 in the convalescent serum and less than 1:10 in acute serum.

Figure 4

Phylogenetic analysis of nucleotide acid sequence of spike gene of SARS CoV viruses Bootstrap values are shown as a percentage. The scale bar shows genetic distance estimated using Kimura's two parameter substitution model. The nucleotide sequences of representative SARS CoV S genes (S gene coding region residue, 3765 bp) were analysed. Viruses sequenced in this study are underlined, and the other sequences used in the analysis can be accessed in GenBank with accession numbers as shown.