New York
Studies of viruses that infect farmyard and domestic animals indicate just how difficult severe acute respiratory syndrome (SARS) will be to tackle, scientists at a New York Academy of Sciences meeting heard last weekend.
Coronaviruses from the same family as that believed to cause SARS can trigger a variety of comparable lung and gut diseases in animals from chickens to cats. Factors that worsen animal infections might suggest why some SARS patients become highly infectious 'super-spreaders' or succumb more easily to the disease, delegates were told.
One tentative theory — that human patients infected with another virus or bacterium develop more severe symptoms when they catch SARS — was backed up by Linda Saif, a coronavirus expert at Ohio State University in Wooster. In unpublished work, Saif has shown that pigs carrying a lung infection before being inoculated with porcine respiratory coronavirus suffer a worse fever and longer infection than previously healthy swine.
Some SARS patients have been found to carry a common respiratory virus called human metapneumovirus. Donald Low, a microbiologist at Mount Sinai Hospital in Toronto, agreed that co-infection with this or another pathogen might exacerbate SARS symptoms, but researchers say that there are too little data on SARS to know whether Saif's work is relevant to humans.
Researchers also discussed the probability that patients who are no longer showing symptoms of SARS could continue to spread the disease. Some national health authorities currently release patients from isolation once their symptoms disappear. But Kathryn Holmes, who studies coronaviruses at the University of Colorado Health Sciences Center in Denver, pointed out that cats infected with a coronavirus can continue to shed the virus for up to seven months after symptoms clear up (A. A. Herrewegh et al. Virology 234, 349–363; 1997).
Saif also discussed research that adds weight to concerns that the steroids commonly used to treat SARS in Hong Kong might instead be exacerbating the disease (see Nature 423, 4; 2003). She warned that dexamethasone, an anti-inflammatory corticosteroid, can actually worsen a coronavirus infection in cows and prolong the period of time for which they release virus (H. Tsunemitsu, D. R. Smith and L. J. Saif Arch. Virol. 144, 167–175; 1999).
Saif also cautioned that researchers have had limited success in producing vaccines against animal coronaviruses. Several studies have shown that experimental vaccines against feline infectious peritonitis virus (FIPV), for example, can aggravate the infection through a phenomenon called antibody-dependent enhancement. Antibodies produced in response to vaccination with FIPV proteins bind to the virus and boost its uptake by immune cells called macrophages. Other viruses are destroyed when engulfed by macrophages, but in this case the FIPV multiplies inside the cells.
This suggests that one possible strategy to fight SARS — collecting and injecting antibodies from recovering patients into new patients — might similarly inflame the disease. Pharmaceutical-industry representatives at the meeting reiterated that the hope of a quick drug or vaccine for SARS is slim. A new antiviral drug would take a minimum of four to five years to reach the shelf, they said, a vaccine closer to six.