The Pandemic Century

by The Pandemic Century- One Hundred Years of Panic, Hysteria

  By now, researchers at several WHO collaborating laboratories were claiming they had also isolated the pathogen of SARS and that it resembled a paramyxovirus, the same type of virus that causes mumps and measles. However, none of these researchers had grown the virus in cell culture or tested it against serum from known SARS patients, so their statements were premature. To know what sort of virus it was, Peiris needed to match it to sequences stored on Gen-Bank, a database managed by the National Institutes of Health that contains a repository of all known viruses. “But you can only do this if you know the sequence of the virus you are looking for and in this case we didn’t know this,” Peiris explained.

  That just left one option: to fish out bits of the viral genome from the infected cells using a random primer. Peiris had asked his colleague Leo Poon to set up this technique to directly test specimens. Now Poon applied the technique to the virus-infected cells in the hope of finding a match with sequences on GenBank. Thirty-five times Poon got fragments of genetic information, but each time the result came back as monkey cell DNA or some other “junk.” By the thirty-eighth attempt Poon was losing hope. Then, on the thirty-ninth attempt, there was a partial match. “It was not perfect, but it seemed to be a coronavirus,” said Peiris. If accurate, this was astonishing news. Coronaviruses are typically the concern of veterinarians. First isolated in 1937, coronaviruses had long been associated with fatal enteric and respiratory infections in pigs, rodents, chickens, and other animals. However, in humans they usually resulted in nothing worse than a sniffle and mild respiratory illness. In short, coronaviruses were considered the “Cinderellas” of the virus world, beautiful to look at after work but too insignificant to take up microbiologists’ daylight hours.

  To be sure there had not been an error, Peiris also spun the fluid containing the virus in a high-speed centrifuge and asked Lim to look at the concentrated virus particles under an electron microscope. Each virus particle was ringed by a halo of tiny spikes as if it were wearing a crown—that too, strongly suggested a coronavirus. Peiris was now confident that SARS was a coronavirus. He speculated that the reason the homology was not perfect was that it was very likely a new type of coronavirus that had emerged recently from an animal reservoir and therefore had yet to be typed by GenBank. Using the partial genetic sequence of the virus, Peiris and his colleagues set up a PCR test to detect the virus, and on March 28 made the test available to hospitals in Hong Kong and to the WHO. “It is not the way we would normally set about it but time was of the essence,” he explained.

  Events now moved rapidly. Within three days of the WHO’s receiving this information, two other laboratories also reported finding the coronavirus, and by March 25 the CDC had uploaded images of the virus to a secure WHO website, prompting Peiris’s group to do the same. Nonetheless, some researchers continued to insist that SARS was caused by a paramyxovirus or perhaps the human metapneumovirus. This prompted speculation that the viruses worked synergistically, with the coronavirus weakening the immune system to the point where the other viruses colonized the respiratory tract, triggering SARS’s distinctive pathology. However, the patients with SARS that Peiris had investigated showed no evidence of metapneumovirus, only the coronavirus. Nor were the coronavirus or antibodies to the coronavirus found in other patients who did not have SARS. Peiris was therefore sure that the new coronavirus was the cause of SARS and that it had been newly introduced to humans, and he submitted a paper to this effect to the British medical journal The Lancet. Researchers at Erasmus University in Rotterdam eventually resolved the dispute by performing an experiment on macaques, one group of which was infected with the coronavirus, a second with the human metapneumovirus, and a third with both viruses. Only the animals infected with the coronavirus developed full-blown SARS. By contrast, the metapneumovirus resulted in only a mild rhinitis, while animals infected with both viruses did not develop worse symptoms than the first group. Ergo, the coronavirus was both a sufficient and necessary cause of SARS.

  It had taken scientists more than two years to discover the cause of AIDS and develop a diagnostic test for HIV, and five months to demonstrate that Legionnaires’ disease was due to Legionella. By identifying the SARS virus so quickly and having a rough-and-ready test at hand, Peiris and other microbiologists were now in a position to say who had the disease and who did not, and hence who presented a risk to the community and ought to be isolated to prevent wider spread.* At a time of growing panic in Hong Kong this was a significant achievement, one that would help health authorities gain the public’s support for quarantines and other vigorous public health measures. Unfortunately, with hundreds of specimens pouring into Peiris’s laboratory every day, he did not have enough staff to run the tests, and when he advertised for additional technicians hardly anyone responded. “Basically, people were scared to work with SARS in case they were accidentally contaminated. It really was a nightmarish situation. It was all we could do to keep our heads above water.”

  If laboratory technicians were wary of the virus, so were other medical workers. Nowhere was the danger of SARS more acute than at the Scarborough Grace Hospital in Toronto. Following his arrival on March 7, Mrs. Kwan’s son had waited twenty hours in the emergency department with only a thin curtain separating him from other patients. When, the following day, he was finally admitted, he was so sick that he had to be rushed to intensive care for intubation. Suspecting tuberculosis, the attending physician isolated him. Unfortunately, during his stay in the emergency room he had been given oxygen and vaporized medications. The result was that a week later a patient who had been in a nearby bed returned to Scarborough Grace complaining of similar symptoms. The patient was immediately isolated and moved to the ICU, where he was intubated by a physician wearing a surgical mask, eye protection, gown, and gloves. But the infection control measures failed and a few days later the physician developed full-blown SARS, followed by three nurses who had been present in the room when the doctor had inserted the tube into the man’s trachea. Worse, the man’s wife had not been asked about her exposure risk and was allowed to wander freely through the hospital’s corridors even though, by then, she was incubating the disease and would also soon fall sick. During her visit to Scarborough Grace she infected six health care workers, two patients, two paramedics, a firefighter, and a housekeeper.

  In the meantime, in mid-March another patient who had been in contact with her husband, and who later presented with symptoms of a heart attack, plus a mild fever, was transferred to York Central Hospital, Toronto, where he became the source of another SARS cluster. Some fifty individuals were eventually infected, forcing the authorities to close the hospital. On March 23 Scarborough Grace followed suit, and anyone who had entered the hospital after March 16 was asked to observe a ten-day home quarantine. By now, guards had been posted at the entrance of the hospital and the city was running out of negative pressure rooms. In an effort to care for patients safely, West Park Hospital recommissioned twenty-five beds in a facility that had previously been used to house tuberculosis patients. Having worked out that SARS was a droplet infection, medical workers were told to apply stringent infection controls, such as handwashing, and wearing gowns, gloves, and N95 masks. Despite these precautions, by March 26 some forty-eight people in Ontario had been hospitalized with “presumptive” SARS and eighteen were confirmed to have the disease, leading to the quarantining of hospitals across the province and the declaration of a “code orange” emergency. All but essential hospital services were suspended in Toronto.

  By now, SARS was dominating the news feeds, with press and TV competing to report every aspect of the outbreak. Toronto was gripped by hysteria. Panicked producers, concerned about their health and the expense of caring for sick crew members should they contract SARS, canceled film and TV shoots. Chinatown became a ghost zone as diners, spooked by rumors of the disease’s Chinese origins, avoided dim sum restaurants and noodle shops. Anyone presenting with suspicious respiratory symptoms was advised to
quarantine themselves at home, and when the child of a nurse from Scarborough Grace exhibited symptoms of SARS, her school shut its gates rather than take the risk of her infecting other children. Yet still, SARS continued to spread.

  Public health officials had no choice but to assume the worst. As James Young, Ontario’s provincial coroner and commissioner of public safety and security, recalled: “We did not know the duration of the incubation period. We did not know whether it was spread by droplet or by air. We had no reliable diagnostic test, no vaccine, no treatment.” Indeed, wandering around Toronto, Young was reminded of a “bioterrorist” attack, the difference being that when a bomb detonated you could see the carnage on the streets, but with SARS there was no “obvious destruction.” Other colleagues feared it might be the harbinger of a pandemic, but “we realized that we simply didn’t know enough about it to tell whether or not this was ‘the big one.’ ” For all the supposed medical progress that had been made since 1918, officials resorted to the quarantine measures that had proved effective in stemming plague and other outbreaks of infectious disease in the eighteenth and nineteenth centuries.

  By April, officials were hopeful the crisis had passed, but shortly before Easter a new cluster of cases emerged among a Catholic sect in Toronto. In response, Ontario’s health department asked clergy to place communion wafers in the hands of congregants, rather than their mouths, and advised priests not to enter confessional booths to take confessions. Then, on Easter weekend, health care workers at Sunnybrook Hospital contracted SARS while performing an intubation on a patient. Three days later, WHO issued a second travel advisory, warning tourists not to visit Toronto unless absolutely necessary. Ontario’s minister of health was outraged and flew to Geneva to try to persuade WHO officials to change their minds, but it was to no avail. Instead, after lifting the travel advisory at the end of April, the WHO reinstituted it in May when a further twenty-six cases unexpectedly emerged at four Toronto hospitals. The result was that it was not until July 3 that the travel advisory was finally lifted. In all, SARS had resulted in 250 infections and 44 deaths in Toronto and Vancouver. That was not a lot when set against the annual death toll from cancer and chronic lung infections. However, in psychological and economic terms, the impact was dramatic. At the height of the crisis, one member of Ontario’s SARS advisory scientific committee recalled waking up drenched in sweat, convinced that “Toronto and Kingston had been consumed by SARS and were desolate.” The hotel industry suffered a 14 percent drop in bookings. Toronto’s film industry, which had enjoyed a record year in 2001, taking nearly one billion Canadian dollars in production money, saw a similar dip in its fortunes. It would not be until 2010 that Toronto’s film industry would rebound to 2001 levels boosted by the remake of the Arnold Schwarzenegger film Total Recall and the depreciation of the Canadian dollar that had occurred in the meantime.

  If SARS was a calamity for Toronto, for Hong Kong it was disaster. Public anxiety had been mounting steadily since the end of March when government officials descended on Amoy Gardens. As officers secured the housing complex with metal barricades and tape, TV viewers were treated to pictures of health workers in biohazard suits guarding the entrance to the high rises as health officials went door-to-door to issue residents with notices informing them that Amoy Gardens was being quarantined and they would not be able to step outside their apartments for the next ten days. The eerie images relayed around the world were the first that many people knew of SARS. The following day, April 1, a fourteen-year-old boy decided to play an April Fool’s prank by posting a bogus message on the website of a local newspaper. The message stated that Hong Kong was about to be declared an “infected port,” that the Hang Sen Index had collapsed, and that its chief executive had resigned. Terrified, people rushed to grocery stores to stock up on rice and other essential commodities, then bolted the doors of their apartments and telephoned and texted those who had not yet heard the “news.” That afternoon Margaret Chan held an emergency press conference in an attempt to reassure the public, but the following day her efforts were undone by the WHO’s declaration that it had issued an advisory warning against unnecessary travel to Hong Kong. Prior to April 2, Hong Kong’s airport had been one of the busiest in the world, processing nearly 100,000 inbound passengers a day. Within weeks passenger numbers had fallen by two-thirds, and by the end of the month Hong Kong was seeing just 15,000 arrivals a day. “Hong Kong is a city gripped by fear,” reported CNN. “A place that markets itself as ‘The City of Life’ and whose lifeblood is travel, trade and international business, is acquiring a reputation as a place of disease.”

  The effects of this fear were far-reaching. In Britain, Hong Kong children attending a boarding school on the Isle of Wight were informed that they would be quarantined on the island following the Easter vacation. At the University of California, Berkeley, Hong Kong students and their families were asked to stay away from graduation ceremonies. Meanwhile, in Switzerland, health officials issued a decree banning anyone who had been in Hong Kong, Singapore, China, or Vietnam since March 1 from attending the World Jewellery and Watch Fair in Basel and Zurich. Hong Kong, which usually mustered the second biggest delegation after the Swiss, threatened to sue, but the Swiss refused to budge, prompting one Hong Kong company to erect a sign over an empty booth that read: “Due to our fear of Swiss Aggravated Respiratory Syndrome we are going home.”

  From an economic perspective, SARS could not have come at a worse time for Hong Kong as the territory was only just beginning to recover from the 1998 Asian financial crisis. The previous year Hong Kong had seen its real GDP grow by 2 percent, and in 2003 the government had been forecasting 3 percent real GDP growth. Within weeks of the WHO’s travel advisory, those forecasts were revised downward as shops reported a halving of retail sales and hotels saw their occupancy rates plunge by 60 percent. As malls emptied and banks like HSBC ordered bond traders to stay home, the only people seen to be doing a brisk trade on the formerly packed streets were salesmen of N95 masks. The sense of panic was palpable. As a lawyer and filmmaker recently arrived in Hong Kong recalled, “It was no longer an animal flu, but ‘Severe Acute Respiratory Syndrome’—an altogether more urban-sounding virus.”

  By now there was little doubt that SARS was spread by respiratory droplets, but could it also be communicated in other ways, through contaminated fecal matter, for instance? And why, if the disease was so infectious, had none of the hotel staff at the Metropole contracted it? The questions recalled the epidemiological puzzle that had confronted CDC investigators at the Bellevue-Stratford in Philadelphia nearly thirty years earlier. Until Peiris’s identification of the coronavirus and diagnostic tests became available, investigators had no way of checking these intuitions. Now, they were in a position to gather samples from different locations of the Metropole and at Amoy Gardens and send them to Peiris’s laboratory to be analyzed. In late April a team of environmental health experts from Health Canada arrived in Hong Kong to assist the Department of Health with its investigation, and on May 16 they reported their findings. The investigators had concentrated their efforts on the ninth floor of the Metropole as this was where most of those who had fallen ill had been staying. In all, genetic material of the SARS virus had been found in 8 of 154 samples. The interior of Liu’s room, 911, had yielded no traces of the virus. However, four positive samples had been collected from the carpet and door sills outside his room and the rooms on either side, suggesting that he may have thrown up when he stepped out of his room or else spread the virus when he coughed in the corridor. In addition, four positive samples were collected from the air inlet fan of the elevator that served the ninth floor. That suggested that Liu’s body fluids had been aerosolized when he entered the elevator, meaning that anyone who stepped out of the ninth-floor lift shortly afterward would have been exposed. However, the investigators dismissed the theory that the virus was transmitted through contact with elevator buttons, door handles, or handrails, pointing out that, if th
at had been the case, then other guests in the hotel, as well as staff, would also have been infected.

  Disappointingly, despite collecting and testing 143 samples from Amoy Gardens, the investigators were unable to recover any genetic material from the SARS virus at the housing complex. However, they noted that the outbreak had begun after a kidney patient who had been receiving dialysis treatment at Prince of Wales Hospital, and who had later developed what the hospital thought was influenza, was discharged and spent several nights at his brother-in-law’s apartment at Amoy Gardens. As well as a fever and a cough, the man had suffered from diarrhea, a symptom that Peiris’s group would later discover occurs in about 10 percent of SARS patients. As the virus had been found in stools for at least two days and the investigators suspected the man had had a high viral load, they speculated that his feces could have been the cause of the outbreak. Noting that many of the drain taps in the bathrooms had dried out or been removed, and that many residents had bought exhaust fans that were six to ten times more powerful than were needed for such a small space, the investigators suggested that contaminated fecal matter could have been sucked into the bathrooms via the sewerage system when people showered. Alternatively, contaminated air from nearby bathroom vents could have carried droplets from adjoining bathrooms via the light well, releasing contaminants through the open windows of apartments above and below. Another factor that may have contributed to the spread of the virus was a sixteen-hour water shutdown that occurred in Block E on the evening of March 21 in order to allow a broken pipe to be fixed. During that period, many residents flushed their toilets with buckets of water, a practice that may have resulted in splashing, increasing the risk of contamination. Overall, the epidemiological evidence suggested that SARS was primarily a droplet infection and that the risk was greatest when an infectious patient coughed or sneezed, propelling infectious particles over distances of about three feet. In many ways, that was good news as it meant that, unlike influenza, SARS did not linger in the atmosphere for long periods, making it an unlikely vehicle for a pandemic. Nor, despite the fears generated by the reports of hospital super spreaders, was it an efficient aerosol, meaning it was unlikely to recommend itself to terrorists. Having said that, at the point when patients develop symptoms—typically two to seven days after infection—they are highly infectious and one person can infect as many as three other people, possibly more if infection controls are inadequate and there is frequent contact between patients and nurses, as occurred in hospitals. Not only that, but SARS had spread efficiently in large buildings, such as the Metropole and Amoy Gardens. Clearly, the virus was a particular threat in urban settings.