Severe acute respiratory syndrome (SARS)--paradigm of an emerging viral infection

Abstract

An acute and often severe respiratory illness emerged in southern China in late 2002 and rapidly spread to different areas of the Far East as well as several countries around the globe. When the outbreak of this apparently novel infectious disease termed severe acute respiratory syndrome (SARS) came to an end in July 2003, it had caused over 8000 probable cases worldwide and more than 700 deaths. Starting in March 2003, the World Health Organization (WHO) organised an unprecedented international effort by leading laboratories working together to find the causative agent. Little more than one week later, three research groups from this WHO-coordinated network simultaneously found evidence of a hitherto unknown coronavirus in SARS patients, using different approaches. After Koch's postulates had been fulfilled, WHO officially declared on 16 April 2003 that this virus never before seen in humans is the cause of SARS. Ever since, progress around SARS-associated coronavirus (SARS-CoV) has been swift. Within weeks of the first isolate being obtained, its complete genome was sequenced. Diagnostic tests based on the detection of SARS-CoV RNA were developed and made available freely and widely; nevertheless the SARS case definition still remains based on clinical and epidemiological criteria. The agent's environmental stability, methods suitable for inactivation and disinfection, and potential antiviral compounds have been studied, and development of vaccines and immunotherapeutics is ongoing. Despite its grave consequences in humanitarian, political and economic terms, SARS may serve as an example of how much can be achieved through a well-coordinated international approach, combining the latest technological advances of molecular virology with more "traditional" techniques carried out to an excellent standard.

Fig. 1

Seroconversion during the course of SARS demonstrated by IFA using SARS-CoV-infected Vero cells. Serum samples from wife of Frankfurt index patient diluted 1:50. (A) 9 days, (B) 12 days, (C) 14 days after hospitalisation (photographs by G. Bauer, Inst. f. Med. Virology, Frankfurt, Germany).

Fig. 2

Electron microscopy image of SARS-CoV particle from infected cell culture supernatant after ultracentrifugation, 2% formalin fixation and negative staining with uranyl acetate (photograph by H. R. Gelderblom, Robert Koch Institute, Berlin, Germany).

Fig. 3

Cytopathic effect (CPE) caused by SARS-CoV in Vero cell culture (A) 0 h, (B) 24 h, and (C) 48 h after inoculation (photographs by G. Bauer, Inst. f. Med. Virology, Frankfurt, Germany).

Fig. 4

Phylogenetic tree of known coronaviruses (provided by S. Günther, Bernhard Nocht Institute, Hamburg).