Will SARS Strike Here?

By MICHAEL D. LEMONICK

The University of Hong Kong's pathology lab is one of the few places on earth where you can stare a newly accused mass-murder suspect right in the face. Researchers there are using a powerful transmission electron microscope to examine a virus that was unknown to science just a month ago. This minuscule particle of protein-encrusted RNA is almost certainly the microbe that had, by last Saturday, infected more than 2,400 people in 19 countries--including up to 115 in the U.S.--and killed at least 89 since it began its rampage through the human population in China last fall. Projected onto a green phosphorescent screen by a beam of electrons and viewed through an optical device that resembles an upside-down periscope, the virus particles--this particular batch came from a relative of the Chinese doctor who became Hong Kong's first fatality on March 4--look chillingly like aliens in a sci-fi film. "There are the little buggers," says Dr. John Nicholls, a pathologist at the University of Hong Kong, leaning aside so a TIME reporter can take a look.

Magnified 100,000 times, the organisms are fuzzy little balls that fill the screen and look like the burrs that stick to your pants during a hike through the woods. You can just make out tiny hooks poking out of the spherical bodies--a telltale characteristic that helps classify the pathogen as a member of the coronavirus family. And while coronaviruses normally cause nothing more serious than a cold, the microbes on Nicholls' slide have evidently, for reasons researchers have yet to discover, mutated into a sometimes deadly infectious agent that has terrified the entire planet.

Since news of the first cases of SARS--short for severe acute respiratory syndrome--began emerging from mainland China a month ago, health authorities around the world have gone on high alert. For the first time in its 55-year history, the World Health Organization (WHO) recommended last week that travelers avoid nonessential trips to an entire region--China's Guangdong province and Hong Kong, right next door--for fear that they might contract and further spread the infectious agent.

But fear of the disease has already outpaced officials' warnings. Tens of thousands of Hong Kong residents venture outdoors only with their faces covered with surgical masks. Airlines have canceled flights in and out of China and Southeast Asia, and financial losses from reductions in tourism, retail spending and other business activity could reach billions of dollars. Schools were closed across affected regions, and last week authorities in Hong Kong forced 240 people from the hard-hit Amoy Gardens apartment complex into quarantine camps outside the city. In Canada, hospitals have closed to control the disease's spread, and health officials everywhere are looking hard at anyone who flies in from Asia and quarantining those with symptoms of infection--a fever of 100.4DEGF or higher, headaches and body aches, a dry cough and shortness of breath.

In the U.S., meanwhile, SARS is the only story other than the war in Iraq that has made it onto just about every news broadcast and front page. Even though nobody has died in the U.S. or even, with a single exception, got extremely sick, Americans are worried that this country could be the next major stop on SARS' international grand tour (see box), prompting President Bush to put SARS on the short list of quarantinable diseases last week.

All of this may seem like an overreaction to an illness that is not nearly as deadly as West Nile virus--SARS kills 3.7% of its victims, compared with West Nile's mortality rate of 6.7% last year--and evidently much less contagious than measles or even the flu. "It's the type of disease that seems to require a lot of direct close contact with somebody who's pretty sick," says Dr. Stephen Ostroff, deputy director of the National Center for Infectious Diseases at the Centers for Disease Control (CDC) in Atlanta.

But what makes SARS so frightening to scientists and the public is how much is still unknown about it, including where it came from, exactly how it spreads, how long its incubation period lasts (and thus how long a victim has been contagious when symptoms appear) and whether a vaccine will ever be available. Infectious-disease specialists are haunted by the great Spanish Influenza pandemic of 1918-19; it killed fewer than 3% of its victims but infected so many that at least 20 million people died in just 18 months--more than were killed in combat in World War I. And until health officials know for sure what they're dealing with, they tend to be overcautious. "When you confront new diseases and they begin to travel widely," says WHO spokesman Dick Thompson, "you have to do everything you can to try to stop the transmission."

If not for the secrecy of the Chinese government, health officials could have acted a lot earlier. It was back in November that a mysterious respiratory illness began spreading through the southern province of Guangdong. Officials hushed up the outbreak to prevent panic, and by February at least 305 Guangdong residents had developed SARS, according to Chinese officials. More cases are thought to have appeared in Beijing and other cities. By the time China finally turned in a two-page report to WHO a month later, the disease was already on the move.

In early March the illness landed in Hong Kong, where patients started showing up at the Prince of Wales Hospital. Hong Kong health officials have become particularly skilled at identifying respiratory diseases because the city is located so near the rich agricultural zones of southeastern China, where pigs, poultry and millions of people live in close proximity. Illnesses like influenza routinely jump from animals to humans, which is why new strains of flu often originate in Asia. Alert to the fact that something strange was going on, authorities in Hong Kong quickly notified WHO and began trying to determine how the disease arrived on the island and how it might be driven off.

The pieces fell into place fairly rapidly. Of the first 45 people to contract SARS in Hong Kong, most had contact with employees of the Prince of Wales Hospital or family members of patients. Those people in turn had contact with a smaller circle who treated or visited a 26-year-old male patient, originally diagnosed with a nonspecific fever. That man, Hong Kong authorities determined, had visited a friend on the ninth floor of the Metropole Hotel in the Hong Kong district of Kowloon in February.

They also discovered that six other people who had stayed on the same floor of the hotel between Feb. 12 and March 2 had SARS too. One of them was a 64-year-old doctor from Guangzhou, the capital of Guangdong. Could he be the source of all the Hong Kong cases? "We believe this hypothesis is justified," says Dr. Margaret Chan, Hong Kong's director of health. At least one other Guangdong man took SARS with him to Spain, while several Metropole victims fanned out across the world to Singapore, Vietnam and Canada. People infected by them in turn spread the disease even farther afield.

Once they realized what was going on, officials at WHO issued an unprecedented global alert and, along with the CDC and other disease labs, launched an impressively coordinated effort to understand the illness as quickly as possible. By examining the victims' body fluids, pathologists at the University of Hong Kong determined that the probable culprit was a mutated coronavirus, although some victims also seem to be carrying a type of paramyxovirus, a member of the family that causes measles. It could be a helper virus that makes the coronavirus more virulent, or it could be an unrelated coinfection. For now, says WHO's Thompson, "we're proceeding as if we know [the cause is] the coronavirus for certain." Both the CDC and Hong Kong University are developing laboratory diagnostic tests for the virus and its antibodies to replace the much less accurate symptom-based diagnoses being used today.

Medical detectives are also trying to understand exactly how SARS is spread. The illness appears to infect the lower lobes of the lungs (unlike common-cold viruses, which typically attack the throat and nasal passages). That's not a good thing: viruses rising from the lungs tend to be distributed in fine aerosols and thus travel farther than the relatively large droplets expelled in sneezes and bronchial coughs. "The data we've heard certainly don't suggest that aerosol transmission is common," says the CDC's Ostroff, "but we keep an open mind to that possibility."

Still, the large number of cases in Hong Kong's Metropole Hotel and Amoy Gardens apartments suggests to Thompson that "there is something going on, a form of transmission that we don't understand." Researchers are concerned that at least some victims--the Chinese doctor at the Metropole and someone in Amoy Gardens, perhaps--are so-called superspreaders. For unknown reasons, some people pass the virus along much more easily than most, perhaps because of the way they cough or the types of contact they have with others or because they carry an unusually heavy load of the virus. Says Ostroff: "We have not seen superspreading in the U.S., but it's a theory that has been advanced in both Canada and Asia." Kwan Sui-chu, the woman who carried SARS from Hong Kong to Canada, is believed to have infected as many as 155 people.

Paradoxically, the existence of superspreaders could be good news: if just a few victims are responsible for the bulk of the outbreak, the disease should be easier to control with aggressive quarantine measures. Some doctors have also postulated that as the virus radiates from the initial patient, it becomes less virulent, meaning that those who come down with second- or third-generation infections may be in less danger. That could explain why in the U.S. nobody has died and only one case has even turned out to be life threatening. Says Dr. Joseph Sung, chief of service at Prince of Wales Hospital: "I'm quite convinced that some people might have contracted the infection but not the disease. Some may develop mild symptoms, like a little bit of cough and no fever; some may just feel a little tired for a day or two."

Mild cases would also act like natural vaccines, conferring immunity on the patients. When 70% or so of a population has immunity--what epidemiologists call herd immunity--a virus is considered burned out: it can't spread further because there is almost no one left to infect. In the meantime, hospitals are trying to prevent the disease from taking root by isolating patients and religiously using gowns, masks, goggles and gloves--techniques that so far have proved extremely effective at preventing transmission.

Still, although the number of new cases in such hot spots as Singapore and Hong Kong finally began to drop last week, nobody is prepared to say that this outbreak is even close to being over, especially considering that many residents of Hong Kong's Amoy Gardens apartments fled before officials could arrive to take them into quarantine. "I don't want to give anybody a false expectation that this is under control," says Ostroff. "This is still a very fluid situation."

So while public-health officials stay on high alert for any new cases, researchers are trying to erase any lingering uncertainty about the ultimate cause of SARS. Several kinds of diagnostic tests are nearly ready. A vaccine against the coronavirus is already under development. And epidemiologists in Asia, Europe and North America are piecing together the natural history of SARS. That last effort should be made a lot easier with the Chinese government's decision last week to finally let a WHO team into Guangdong. Medical detectives may have already found the very first recorded victim--patient zero--a man in the city of Foshan who passed the virus on to four people before he recovered.

Even if all these measures fail to eliminate SARS quickly or completely, they should at least minimize the danger. "People should be concerned," says Ostroff. "But I don't think they should be alarmed." The minuscule murderer in Dr. Nicholls' microscope sights is still potentially deadly. But it no longer looks like the monster it appeared to be just a few weeks ago. --Reported by Jim Erickson, Carmen Lee and Bryan Walsh/Hong Kong, Sora Song/New York, Matthew Forney/Beijing and Daffyd Roderick/Toronto

With reporting by Jim Erickson, Carmen Lee and Bryan Walsh/Hong Kong, Sora Song/New York, Matthew Forney/Beijing and Daffyd Roderick/Toronto