The Truth About SARS

By Michael D. Lemonick and Alice Park

So far, the U.S. has been lucky. It has been nearly six months since the SARS outbreak emerged and more than six weeks since the illness spread from its birthplace in southern China to put the world on alert. Yet with more than 4,800 cases in at least 26 countries to date, a disease that has rocked Asian markets, ruined the tourist trade of an entire region, nearly bankrupted airlines and spread panic through some of the world's largest countries has largely passed the U.S. by. Hospitals and schools were shut down last week in Beijing, thousands of people were put under quarantine, and rumors flew through the capital that martial law was about to be imposed. But in the U.S., only about 40 people are believed to have severe acute respiratory syndrome, or SARS. The number of cases doesn't seem to be growing, and--most reassuring of all--as of last Saturday, not a single victim had died.

But if Americans think that they have dodged the biological bullet, they had better think again. As the truth about SARS comes out--slowly, due in large part to government cover-ups in the land of its birth--it is becoming clear that what is taking place in Asia threatens the entire world. Epidemiologists have long worried about a highly contagious, fatal disease that could spread quickly around the globe, and SARS might end up confirming their worst fears. Microbes can go wherever jet airliners do these days, so it is a very real possibility that the disease has not yet shown its full fury. "We don't know the reason that we've been lucky so far," says Dr. Julie Gerberding, director of the U.S. Centers for Disease Control (CDC), "but we're not taking any chances."

Americans should not count on their sophisticated health-care system to protect them. China may be relatively backward, but Hong Kong, with a modern medical system, has experienced about as many deaths as have been reported in the rest of China put together. And only a few hours' drive from Buffalo, N.Y., or Detroit, just across the Canadian border, a Western city that thought it had done just about everything possible to contain its outbreak keeps losing ground. A few weeks ago, Toronto believed that the epidemic was winding down. Now, with 20 deaths, it's the first place outside Asia to be put on a do-not-visit list issued by the World Health Organization (WHO)--a public humiliation that infuriated Toronto residents. ("I've never been so angry in my whole life," declared Mayor Mel Lastman.) Beijing and Shanxi province also joined the list last week; Hong Kong and Guangdong province, where the outbreak began, have been on it for weeks.

With fewer than 300 known SARS deaths so far, the worldwide toll is tiny compared with, say, the 3 million people who died of AIDS last year. But if SARS continues to spread, its numbers could skyrocket. Its overall death rate of about 6% is far lower than that of AIDS, Ebola or malaria, but if enough people catch the illness, even a low rate could cause a catastrophe. The Spanish flu epidemic of 1918-19 had a death rate of less than 3%, but so many people became infected that it killed more than 20 million people in just 18 months.

The financial toll, meanwhile, is already catastrophic. Economists predict that China and South Korea could each suffer some $2 billion in SARS-related losses in tourism, retail sales and productivity. Japan and Hong Kong stand to lose more than $1 billion apiece, and Taiwan and Singapore could lose nearly that much. In Canada, meanwhile, J.P. Morgan Securities Canada estimates that Toronto is losing $30 million a day. All told, says WHO, the global cost of SARS is approaching $30 billion.

And nobody can forecast how much worse it could get. The more victims there are, the greater the chance that SARS will spread--and there may be a lot more cases in China than anyone realizes. It's hard to gather information in such a vast country under the best of circumstances, but the actions of Chinese officials have made the situation worse. In April the government finally grudgingly admitted that SARS is a problem and belatedly allowed in a WHO team to investigate. Soon doctors at Beijing hospitals began leaking word of a massive cover-up. The country's Health Minister and the mayor of Beijing were dismissed last week from their jobs and their Communist Party posts. Chinese officials have revised their numbers, but they are still not telling WHO about patterns of spread. "Right now," says Jeffrey McFarland, a member of the Beijing WHO team,"we're getting exactly the same information as the press."

--CURBING THE SPREAD

Beyond that, the physical mechanism by which SARS is spread is still unclear. In mid-March, Hong Kong officials thought they knew how to control the epidemic. Since SARS seemed to require close contact with a victim, anyone suspected of infection was quarantined, and doctors and nurses were careful to wear protective clothing when dealing with patients. Then came Amoy Gardens. Clusters of cases began proliferating in the giant, 33-floor apartment towers in Hong Kong. Ultimately, more than 300 residents of the complex came down with SARS (at least 15 have died), even though many of them seemed to have had no direct contact with one another.

In fact, despite intensive research in labs all over the world, scientists still have more questions than answers about SARS and the coronavirus that causes it. So while teams from WHO are helping health workers on the front lines, other scientists are redoubling their efforts to understand SARS' natural history.

One mystery is where the disease came from. Coronaviruses have long been known to veterinary medicine because they routinely infect livestock, ducks and other domestic animals. In humans they had never caused anything worse than a cold, but this strain is clearly different. Given belated access to Chinese records just three weeks ago, WHO teams are looking carefully at the records of human cases. They also plan to conduct more detailed studies of unusual infections in animal populations. If they can find the animal hosts, they might be able to prevent new animal-to-human transmissions.

Meanwhile, top virologists in the U.S., Canada, Hong Kong, Germany and several other nations have linked up to create a sort of virtual research lab. Their goal: to understand the virus itself. They identified the SARS virus several weeks ago, and now they are trying to come up with diagnostic tests. That's crucial. Early SARS cases present the same fevers, muscle aches and diarrhea as flu victims, and without a way to distinguish between them, the public-health system could be quickly overwhelmed.

The virtual lab and independent biotech companies have already come up with several tests, but they are not yet reliable enough to be widely deployed. Canadian microbiologists reported last week that as many as 40% of their SARS patients did not test positive for coronavirus. That might be because their tests are not sufficiently sensitive or, even more worrisome, because the coronavirus has mutated enough to elude detection.

Yet another open question is precisely how the disease spreads. Doctors first concluded that the agent responsible for SARS is transmitted by droplets expelled by coughs or sneezes. After the burst of cases in Hong Kong's Amoy Gardens complex and the particularly aggressive spread of SARS in Toronto among health-care workers, however, scientists now speculate that there may be other mechanisms as well. In Amoy Gardens, for example, transmission may have occurred via contaminated fecal matter leaking from a broken sewage pipe. That would explain the lack of direct contact, as well as the fact that all these cases, unlike those in mainland China and Toronto, are characterized by severe diarrhea.

--RAPID MUTATION

It may also be that the microbe has mutated into several subtly different strains producing different symptoms. This might explain some of the perplexing transmission patterns seen on planes: people sitting next to SARS victims did not always get infected, while those across the aisle sometimes did. Perhaps the latter had used a lavatory immediately after an affected passenger.

Multiple strains would not be surprising. This bug's genetic code is based on RNA, a single-stranded molecule very similar to DNA. Unlike DNA, however, RNA has no built-in proofreading mechanism to fix mistakes in the replication process. Most of these don't amount to anything, but every once in a while an error may make the microbe more infectious. Beyond that, says Dr. Robert Webster, chief of virology at St. Jude Children's Research Hospital in Memphis, Tenn., "when a virus comes across to a new host, what does a virus do? It varies like crazy."

In Toronto health-care officials are especially alarmed by the high number of SARS cases among health-care workers who had taken all the recommended precautions, including wearing gloves, masks and gowns and vigorously washing their hands. The problem there may have been fatigue and complacency in the changing room. CDC scientists reported last week that the virus can survive as long as 24 hours outside the body: doctors and nurses who touch their protective gear while changing into regular clothing may be unwittingly exposing themselves and others to the coronavirus.

Another factor scientists do not understand is the superspreader, a person who appears to pass the disease on with extraordinary efficiency. Part of the explanation may be in the individual's genetics. "We don't know what those genetic factors are yet," says Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases (NIAID), "but they're not necessarily related to how sick the person is." Some experts suspect that superspreaders might have a more virulent strain of coronavirus or be co-infected with other microbes. Having multiple infections may, these scientists speculate, increase one's chance of passing on the disease.

The risk of death from SARS, meanwhile, may have less to do with a particular strain of the virus and more to do with the body's reaction to it. "The immunological and inflammatory response of the body," says Fauci, "could be contributing significantly to the damage in the lungs." But nailing that down, along with questions of whether survivors become immune to further infection and whether the disease is permanently with us, like AIDS, will take more research.

So will the search for a vaccine. The biotech company GenVec announced plans last week to collaborate with NIAID to insert portions of the coronavirus genome into a weakened cold virus. If the proteins generated by these snippets are powerful enough to trigger an effective immune response, then the resulting vaccine might be successful. NIAID is also coordinating separate U.S. government efforts to develop vaccine candidates. And the U.S. Army Medical Research Institute for Infectious Disease is screening thousands of compounds to see if any might slow or stop the disease.

--WILL IT BREAK OUT HERE?

With any luck, SARS won't hit the U.S. hard until some of these loose ends are tied up. Airlines have handed out more than 500,000 yellow health-alert cards from the CDC that tell passengers arriving from SARS-prevalent areas what symptoms to be alert for and whom their doctors can call; the CDC has also posted on its website detailed information for health-care workers.

But that may only put off the inevitable. While the U.S. is better equipped than most countries to detect and contain epidemics, it's pure luck that it has not been hit harder. So far, none of the handful of people who have carried the virus to the U.S. from Asia have been superspreaders. And health-care workers in the U.S. have not yet made any of the mistakes that tripped up the Canadians: a patient transferred from an affected hospital to an unaffected one, lax enforcement of isolation orders, hospital workers who may not have been vigilant enough with protective gear.

The more time that passes, the better the U.S. can learn from the experience of other countries. But as long as there are even small pockets of infection lingering anywhere in the world, an outbreak is always a threat. In a world as interconnected as ours, it may just be a matter of time before SARS strikes in the U.S. the way it has elsewhere. "It's too soon to count our chickens," says Fauci. "This is an evolving epidemic, and we need to take it very seriously." --Reported by Steven Frank and Daffyd Roderick/Toronto, Matthew Forney/Guangzhou and Susan Jakes and Huang Yong/Beijing

With reporting by Steven Frank and Daffyd Roderick/Toronto, Matthew Forney/Guangzhou and Susan Jakes and Huang Yong/Beijing