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Comparative Study
. 2004 Jan 10;363(9403):99-104.
doi: 10.1016/s0140-6736(03)15259-2.

Molecular epidemiology of the novel coronavirus that causes severe acute respiratory syndrome

Y Guan  1 , J S M Peiris, B Zheng, L L M Poon, K H Chan, F Y Zeng, C W M Chan, M N Chan, J D Chen, K Y C Chow, C C Hon, K H Hui, J Li, V Y Y Li, Y Wang, S W Leung, K Y Yuen, F C Leung
Affiliations
Comparative Study

Molecular epidemiology of the novel coronavirus that causes severe acute respiratory syndrome

Y Guan et al. Lancet. .

Abstract

Background: Severe acute respiratory syndrome (SARS) is a newly emerged disease caused by a novel coronavirus (SARS-CoV), which spread globally in early 2003, affecting over 30 countries. We have used molecular epidemiology to define the patterns of spread of the virus in Hong Kong and beyond.

Methods: The case definition of SARS was based on that recommended by WHO. We genetically sequenced the gene for the S1 unit of the viral spike protein of viruses from patients with SARS in Hong Kong (138) and Guangdong (three) in February to April, 2003. We undertook phylogenetic comparisons with 27 other sequences available from public databases (Genbank).

Findings: Most of the Hong Kong viruses (139/142), including those from a large outbreak in an apartment block, clustered closely together with the isolate from a single index case (HKU-33) who came from Guangdong to Hong Kong in late February. Three other isolates were genetically distinct from HKU-33 in Hong Kong during February, but none of these contributed substantially to the subsequent local outbreak. Viruses identified in Guangdong and Beijing were genetically more diverse.

Interpretation: The molecular epidemiological evidence suggests that most SARS-CoV from the outbreak in Hong Kong, as well as the viruses from Canada, Vietnam, and Singapore, are genetically closely linked. Three viruses found in Hong Kong in February were phylogenetically distinct from the major cluster, which suggests that several introductions of the virus had occurred, but that only one was associated with the subsequent outbreak in Hong Kong, which in turn spread globally.

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Figures

Figure 1
Figure 1
Epidemiological data on selected key virus isolates Schematic representation of the relations between the key patients and the outbreaks in different regions of the world. Dotted arrows indicate uncertain transmission route, and grey boxes indicate regions of outbreaks. Designations of the viruses are shown in parentheses. The clinical and epidemiological relations of some of these patients have been described previously. In reference 17 these patients were designated as: patient 1=patient 1; patient 2A=patient 2; patient 3A=patient 6; patient 3B=patient 7.
Figure 2
Figure 2
Phylogenetic analysis of 169 SARS-CoV isolates Numbers at nodes indicate bootstrap values (%). Branch length shows the genetic distance with reference to the horizontal scale bar. For convenience of display of a large number of isolates, field isolates with zero genetic distance compared with their subcluster (B1, B2–1, and B2–2) common ancestors are replaced by the subcluster name with the number of isolates shown in parentheses (highlighted in blue). The full phylogenetic tree of the 169 isolates is available at http://image.thelancet.com/extras/03art5344webfigure1.pdf. Viral gene sequences highlighted in red represent key isolates described in figure 1. Sequences previously available in Genbank are shown in bold and italic. Subcluster names are shown on the right of the tree. Total numbers of isolates included in the cluster are shown in brackets. Cluster transition isolates are indicated by blue dotted arrows. Epidemiological details of key viruses are provided in table 1 and figure 1. Other viruses sequenced as part of this study are prefixed with F, M, or A, to represent the month of sample collection (February, March, or April). Sequence alignment of the recurrent critical point mutations that distinguish the groups and subgroups are shown on the right of the tree. All these mutations are non-silent except at 1026 and 1068 (highlighted in green).
Figure 3
Figure 3
Nucleotide and aminoacid substitutions of SARS-CoV isolated in Amoy Gardens Comparisons were made with other virus isolates by full genome sequence alignment. Except for the Hong Kong and Guangdong samples, the index case or first uploaded sequence from other cities and countries was chosen. Nucleotides were numbered on the basis of the HKU-39849 full sequence. Slash indicates that the sequence data are not available, and nucleotides highlighted in yellow are those that differ from the majority at the corresponding location. Only substitutions occurring in more than one virus are shown.
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