Editorials

Severe acute respiratory syndrome revisited

Coronavirus may be responsible, but new information arrives every day

See also Papers p 850

Severe acute respiratory syndrome is an infectious disease in humans that was first recognised in south east Asia in late February 2003.¹ Given the disturbing features associated with the diseasewhich include poorly defined pathogenesis, absence of laboratory diagnostic testing, and failure of known antimicrobial treatmentsits emergence prompted the World Health Organization to issue the first global health alert for over a decade. An insidious and non-specific onset and incubation of up to 10-11 days are ingredients that favour community transmissionindeed, early epidemiology indicates spread along international air routes. However, a high proportion of illness has occurred in close contacts of affected individuals, which indicates spread through body fluids and secretions rather than aerosol routes. Despite rigorous procedures for infection control, transmission has continued in Hong Kong, Singapore, and Canada. This has resulted in yet more rigorous quarantine procedures, which have started to affect the economic life of those areas by reducing travel and trade and by inducing serious concerns in the population.

What have we learnt in the month since the global health alert? As part of its global pandemic plans WHO mobilised the scientific and intellectual resources of 11 laboratories in nine countries.² Each laboratory has a track record of supporting WHO investigations and broad expertise in the detection and diagnosis of pathogens, as well as a commitment to ensuring release of data into the public domain to expedite the search for the agent that is responsible for severe acute respiratory syndrome. In a very short time this network of laboratories has identified at least two ribonucleic acid viruseshuman metapneumovirus and an unusual coronavirus that is currently termed severe acute respiratory syndrome associated coronavirus.³

Human metapneumovirus, although recognised in 2001, is not a new virus in humans since almost all children show evidence of infection by 5 years of age. The virus is usually recognised in association with acute respiratory illness in young children. Our understanding of illness associated with this virus in adults is limited, although evidence shows that a spectrum of severe illness in adults is unlikely unless underlying factors such as immunosuppression are at play. The discovery of this virus in the early days of this investigation was compatible with the preliminary description of the paramyxovirus-like particles seen in Germany in patients with the syndrome. Nevertheless investigations of this nature require an open mind. Only a few days later the first reports emerged in the laboratory network of coronavirus-like particles being seen in this syndrome. Molecular analysis indicated a novel coronavirus. The limited data so far do not allow more precise classification, although it will not be long before several laboratories complete sequencing the whole viral genome. The speed at which information is being delivered, now that some tools for detection are available, matches the speed at which the virus is being transmitted, although it is still a step behind the global march of the virus.

Do we have enough evidence to say that the coronavirus is the aetiological agent of severe acute respiratory syndrome? The data are beginning to stack up from a variety of different sources. The questionwhat is necessary and sufficient to cause severe acute respiratory syndromemay even be answered in a few weeks. We will need to integrate information obtained from epidemiological investigations and laboratory analyses to provide a coherent picture of the overall syndrome as well as perform some "challenge investigations" in appropriate model systems in vitro. So far the epidemiological investigations have been running in parallel with the laboratory approaches.

As the first generation of diagnostic tests for the detection of coronaviruses comes into worldwide use, key questions relating to the transmission of this disease can be addressed with careful studies on virus shedding in different body fluids, and with antibody studies to determine whether asymptomatic individuals have been exposed to the virus. The results of these studies will inform infection control procedures and improve the blunt public health measures currently imposed. The information thus gained will allow risk assessment regarding the spread of a novel infectious agent with a potentially fatal outcome.

Where does that leave the human metapneumovirus? There is evidence of dual infection in several of the Canadian patients with severe acute respiratory syndrome.⁴ This observation leads to many possible speculations about the role of human metapneumovirus in severe acute respiratory syndrome, which will take a little while to disentangle. It will be important to understand whether individuals who have had both infections simultaneously have had more severe disease or particular pathological features in their illness, and whether one virus predisposes to another. The observation also reinforces the view that it is important to keep searching for microbiological agents in affected individuals since there may be yet more to uncover.

Clearly, there is much to do both epidemiologically and virologically to contain the global spread of severe acute respiratory syndrome. Let us hope that the worldwide efforts to understand the nature of the causative agent(s) and prepare tests for detection will outpace the relentless daily accumulation of cases worldwide.

Maria Zambon, deputy director. 

Enteric, Respiratory and Neurological Virus Laboratory, Health Protection Agency, London NW9 5HT, (mzambon{at}phls.org.uk)

Footnotes

Competing interests: None declared.