Issue cover-dated August 21, 2003

Our Future With Sars

The masks are off. Cities around the globe from Guangzhou to Toronto have celebrated the end of an outbreak of Severe Acute Respiratory Syndrome that infected more than 8,000 people worldwide, killing more than 800. Unfortunately, few viruses in history have infected humans just once and disappeared. Now some of the world's top scientists are busy working out just when, how, whom and how severely Sars could strike next.
In this special report, the REVIEW delivers the most up-to-date information on Sars today, five months since the virus got its name. We explore the world of Sars from the wild-animal markets of China's Guangdong province to the newly refurbished hospitals of Hong Kong to the laboratories where scientists are rushing to develop diagnostic tests, treatments and vaccines.
We look at the broad impact of the disease on economies and on governments, from China's public-health failures to Singapore's careful monitoring and containment policies. And we visit victims suffering the lingering effects of the disease. This is our future with Sars.

By Geoffrey A. Fowler/HONG KONG and Ben Dolven/SHANGHAI

Will Sars return?
Yes, Sars will likely return. Scientists disagree over where it might be hiding, and can't say that it's gone for good. "I don't think this virus has been eradicated," says Hitoshi Oshitani, leader of the World Health Organization's regional Sars outbreak response-and-preparedness team. Current cases are few, but as recently as August 11 a woman died of Sars in Toronto. With a high probability that it still exists in animals, "there is a chance that the virus could cross the human barrier again," he says.
How bad will it be?
Scientists predict an outbreak that's not as bad as the last one, because even if we can't stop the first infection, they say, we can prevent it from spreading.
The outbreak is more likely to be small and localized--but only if the virus doesn't first re-emerge in a pool of people without proper medical care, and if public-health mechanisms of quarantine and animal control work as they've been designed to stop the spread of Sars.
Researchers believe the quarantines effectively halted human-to-human transmission. "In reality, transmission of Sars was not that efficient compared to the flu," says microbiologist Malik Peiris of the University of Hong Kong. And because the disease is less easy to transmit in its earlier stages than in its later ones, even haphazard quarantines can be effective at breaking the chain of transmission.
Of course, scientists have not ruled out all doomsday scenarios. They still don't understand how the people known as "super-spreaders" infected so many at the Metropole Hotel and Amoy Gardens housing estate in Hong Kong. And one scary aspect of the Sars virus is its ability to mutate: So far, scientists know of up to 14 variations of the virus's gene.
When will Sars be back?
By one theory, the Sars virus went away simply because the weather changed. Other ribonucleic acid-based viruses such as flu disappear in the summer to return in the winter. Why? "This has been a big question," says Ralph Baric, a professor at the University of North Carolina who for 20 years has studied the coronavirus--of which the Sars virus is one example. He suspects that viruses are more stable with the lower temperatures, humidity and ultraviolet light of winter--when people also tend to huddle indoors, spreading germs.
If Sars is seasonal, that would help explain why the virus was more difficult to control in Toronto in March and April, yet seemed to disappear more easily from China in May and June. It would also raise worries that the recent outbreak was a mild preliminary "herald wave," such as the one for flu in the spring of 1917 that preceded the outbreak in 1918 that killed more than 20 million people around the world.
On the other hand, February is the peak of the flu season, but Sars didn't peak until April. That's a strike against the seasonal theory--though not one that discounts the return of the disease.
Can Sars be stopped?
If the virus is being carried by animals, and if scientists can't determine precisely how, then it will be impossible to prevent another jump to humans. But if researchers can discover how the virus made its initial jump from animals to humans then public-health authorities could try to make sure it is less likely to happen again by fixing hygiene and animal husbandry practices. Still, while that might work in Singapore or even Hong Kong, in China it'll be a tall order.
How can we halt an epidemic?
Health authorities now understand that rigorous isolation of patients and the people who have been in contact with them is critical to stopping transmission. Isolating real Sars cases from flu cases could become a major concern this winter: There still is no quick diagnostic test that can identify a Sars case in the early stages of infection.
And if the virus does return, it's most likely to start in a population that is under the radar of the public-health infrastructure, says Ralph Baric of the University of North Carolina. "They could be poor, or geographically isolated, so they don't have easy access to health care. They could become a reservoir, and it would spill out," he says. Baric's description applies to much of southern China, where Sars is believed to have originated.
Border health checks might also slow an international pandemic. Hong Kong, though it was taken off the WHO's list of Sars-affected places in June, continues to require a written health declaration and temperature screening of all incoming and outgoing travellers from the territory. Since it began screening in April, Hong Kong has checked the temperature of 24 million passengers with infrared thermal-imaging systems.
To date, two passengers with Sars have been caught by the Hong Kong border checks, both in April; notably, they were isolated through written health declarations, not temperature checks.
Scientists also say that governments should do more to regulate animal husbandry and wild-animal markets, even if locally it is politically unpopular.
The other important step is better protection and preparation among health workers. The WHO reports that some 20% of Sars cases were among health workers, and a particularly large proportion of the early infections occurred in hospitals. So lowering the number of medical-worker infections alone "would be enough to keep a lid on it," says Meirion Evans, a British epidemiologist who led one of the WHO teams to China's Guangdong province. That means health-care workers must have the right equipment to protect themselves.
Hong Kong is spending HK$400 million ($51 million) to put 1,280 isolation beds in nine public hospitals, and spending HK$100 million to re-train medical staff. Yet Hong Kong's Medical Association president, legislator Lo Wing-lok, has said the city needs more intensive-care facilities and equipment and that it will take at least three years to fully train all medical staff.
The United States is no better prepared than anyone else. So why did no one die of Sars there this spring? Only eight U.S. patients yielded laboratory evidence of the Sars-associated coronavirus, according to the U.S. Centres for Disease Control--statistically not enough cases to produce a death from an illness that killed fewer than one in 10 patients. "They were just very lucky," says Dr. David Hui of the Chinese University in Hong Kong.
The U.S. can't plan on being lucky next time. The General Accounting Office of the U.S. Congress in July concluded that a major outbreak, particularly during the flu season, could strain hospitals and lead to severe overcrowding. "Few hospitals have adequate staff, medical resources, and equipment, such as N-95 respirators, needed to care for the potentially large numbers of patients that may seek treatment," the GAO said in the report.
Is there a treatment?
After more than 8,000 cases there is still no "golden standard" for Sars treatment, says Hitoshi Oshitani of the WHO. But some lessons were learned, and some promising discoveries have been made.
During the confusion of the initial outbreak, doctors weren't able to set up the controlled, randomized placebo experiments that they require to really understand treatment. Nonetheless, by tracking treatments doctors have identified some patterns that will enable them to set a new regimen.
In Hong Kong, a combination of the antiviral drug Ribavirin combined with the Aids drug Kaletra--a protease inhibitor that cuts the ability of the virus to replicate itself--will most likely be delivered from the onset of the disease. Singapore doctors are also likely to try treatment with interferons, proteins to ward off infection of healthy cells and stop the virus from multiplying.
Too much Ribavirin caused red blood cells to break down (a disorder called haemolytic anaemia), especially in Toronto hospitals, which used much higher doses. Steroids, too, may be used to help the body fight lung injury, but only in later stages of Sars, as steroids given too early might prolong viral replication.
Working with blood from recovered patients and maps of the coronavirus genome, some labs have begun designing new drugs to fight Sars. Some of the drugs are designed to change the virus's ribonucleic acid, others slow down its replication, while still others replicate the antibodies that the body uses to fight the virus.
Among the most promising discoveries, United States Aids researcher David Ho has worked with Hong Kong scientists to develop a kind of chemical scissors--peptides--to cut the spread of the virus in human cells. Now he needs to find the right way to test his drugs on animals. "We have been in a holding pattern awaiting the development of the monkey model for this work to proceed," he says--so his drug likely won't be ready if Sars returns this winter.
How can I protect myself?
Despite the new scientific research on Sars, the steps that doctors recommend will sound familiar. People should wear masks in hospitals and doctors' offices, where Sars infections occurred most often last time. Sars is easily confused with flu, so health officials around Asia are requiring flu vaccinations for all health-care workers, and recommend the same for the elderly and others at risk of contracting it.
"Keep a close ear on the ground" for word from health authorities about the return of Sars or any infectious disease, suggests Dr. Poh-Lian Lim of Singapore's Tan Tock Seng Hospital. She recommends the Web sites of the U.S. Centres for Disease Control ( and the WHO, ( for accurate information that isn't too technical.
Where will the next outbreak come from?
Where the virus will come from depends on who's got it. That puts the spotlight on people, animals and laboratories.
Even now, some scientists want to ensure that Sars isn't being spread by people with very low levels of the virus and without noticeable symptoms. Hong Kong is planning a test to determine just that. In one unlikely scenario, the virus or a mutated cousin could flare up suddenly in thousands of such carriers.
Researchers in mainland China and Hong Kong are busily studying animals in southern China, where the virus is thought to have originated. Most likely, say epidemiologist Meirion Evans of the WHO and most other researchers in Asia, in autumn the virus could jump back to humans from its hiding place in an animal reservoir, including the civet cat.
Then there's the frightening possibility that the Sars virus--or a stronger mutated strain--could be inadvertently released by a hospital or lab researching a diagnostic test or treatment. Labs in China are already conducting vaccine tests on monkeys, a risky proposition because this creates new opportunities for human infection in the lab.
David Ho, a noted U.S. Aids researcher who is working on Sars with labs in Hong Kong and China, calls this possibility "a huge concern." In China, he says, "over two dozen labs are growing up buckets of virus," which means that labs need better protective equipment and better-trained personnel.
David S. Perlin, scientific director of the U.S. Public Health Research Institute, disagrees. "The international biomedical community has been extremely responsible when working with emerging infectious disease agents," he says. The Chinese government is reportedly in the process of establishing which of several dozen labs have stores of the virus, and may decide to store those samples centrally to avert a leak.
Where's the vaccine?
After improving the public-health infrastructure and surveillance, the best weapon against Sars would be a vaccine, which might also be useful as a treatment. But a vaccine won't be available for at least three years, and possibly longer. In fact, nobody has attempted to develop a coronavirus vaccine for humans for decades because until now coronavirus infections rarely killed people.
Also, developing vaccines is expensive. Small bioengineering companies have begun research, but United States Aids researcher David Ho and others worry that pharmaceutical firms are not interested in spending millions of dollars to turn scientific leads on Sars into drugs without clear evidence that Sars will return in a big way. "The drive to develop drugs is largely gone," Ho says. "There is no perceived market for this."
How would it work?
Vaccines are harmless versions of a virus injected to encourage the immune system to develop antibodies. There are three major strategies to developing a Sars vaccine.
The most hopeful and basic strategy: Create a live but weakened form of the virus, as with the vaccines for polio and yellow fever. The danger is that the mutation-prone Sars virus could become more lethal once inside people.
Another approach: Grow the virus in the laboratory, kill it, and then inject it as a vaccine. But growing large amounts of a deadly virus is dangerous, and any of the virus that avoids being killed could start a new outbreak after it is injected.
A third approach: a gene-spliced vaccine in which scientists would create a new version of the virus, or a harmless "vector" virus carrying one or two important genes from the corona-virus. The laboratory-created virus could be just enough to encourage the body to develop needed antibodies without getting sick. This approach could backfire, too, if it causes "partial immunity," an unbalanced immune response that could actually enhance the disease, says Ralph Baric of the University of North Carolina.