NEW YORK—Many of us have watched with both fascination and horror as the severe acute respiratory syndrome (SARS) has made its way around the world. Its rapid spread has amply illustrated the dangers of globalization—but has just as amply demonstrated the effectiveness with which international health agencies can now respond to a new threat. In less than two months, a likely cause has been identified and genetically sequenced. Diagnostic tests are being developed, and the organism’s transmission methods are being elucidated.

Of course, much more work remains to be done. The syndrome has not been fully characterized, and treatment remains empiric (see related story in this issue). The efficacy of many of the measures put in place to control SARS’ spread is unclear. However, the speed with which the new virus was identified gives hope that it may be possible to develop effective treatments and to slow transmission of this highly contagious disease.

ORIGINS OF THE EPIDEMIC

The first known case of what is now called SARS was diagnosed last November in Foshan, a small industrial city in Guangdong province in southern China. A businessman was hospitalized with atypical pneumonia; four health care workers who treated him also contracted the disease.

The disorder spread rapidly in China, but no reports were made to the WHO until early February. By the end of that month, infected patients had arrived at hospitals in Hong Kong, Vietnam, and elsewhere in southeastern Asia. In early March, cases began to appear in Toronto; additional cases were then detected in Vancouver. By early April, suspected or confirmed cases had been reported in more than 20 countries and more than 30 US states.

On March 12, the WHO issued a global alert about SARS. Investigators from around the world had already begun working to identify the cause, but after March 12, they joined together in an unprecedented display of international cooperation.

NEW VIRUS IDENTIFIED

On March 24, researchers from Hong Kong[1] and the CDC[2] announced that they had identified a novel coronavirus as a likely cause of SARS. Shortly afterward, a European team[3] announced that they too had isolated the coronavirus.

The Hong Kong group identified the enveloped, single-stranded RNA virus after examining nasopharyngeal aspirate and lung tissue specimens from two infected residents of their city. The CDC investigators isolated the virus in a variety of specimens taken from a Vietnamese patient. The European team detected the virus in respiratory and blood samples from a Singapore physician and his wife, both of whom had SARS.

These groups and others have since found the virus in additional SARS patients. For example, the Hong Kong group detected the virus in 45 of 50 SARS patients but in none of 40 controls. A similar analysis of patients from Hanoi identified coronavirus in all five of those with probable SARS and in three of 13 patients with possible SARS, but in none of the 21 healthy controls. The CDC investigators detected the virus in 19 SARS patients from the United States and five Asian countries. Coronavirus has also been detected in several Canadian patients.

The CDC team has proposed that the virus be named Urbani SARS-associated coronavirus in honor of Carlo Urbani, MD, an Italian physician working in Hanoi who was the first to recognize the importance of the new syndrome. Tragically, Dr. Urbani contracted SARS and died on March 29.

UNKNOWN SOURCE

The source of the new pathogen is presumed to be an animal virus. However, genetic sequencing of the organism, first completed in mid-April by a Canadian team, provides no clues to its parent; it is equally distant from several animal coronaviruses. Within days of the Canadian team’s announcement, several other groups reported that they had also completed genetic sequencing of the coronavirus. The four strains that had been analyzed as of April 20 showed minor variations in amino acid sequence, suggesting that the virus may be capable of undergoing change or expressing alternate proteins.

There are two pathways through which the new pathogen may have arisen. The original organism may have mutated, allowing it to “jump” to humans. However, many coronaviruses can adapt genetic material from closely related pathogens; such recombination may have been the path through which the new virus was created.

Identification of the new virus did not establish proof that it causes SARS. That requires two additional steps, explained Julie L. Gerberding, MD, MPH, Director of the CDC. “First of all, we [must] unequivocally demonstrate coronavirus in the affected tissue. We’ve seen the virus in tissue and we’ve seen evidence of pneumonia, but we need to see them both together.” In addition, researchers must be able to use the new virus to re-create the infection in an animal.

The latter steps were quickly completed. By mid-April, a group at Erasmus University in Rotterdam, led by Albert Osterhaus, DVM, announced that it has succeeded in infecting some monkeys with the new coronavirus, and that the resulting infection was quite similar to human SARS.

Coronavirus may not act alone, however. Said J. S. Malik Peiris, MD, principal author of the Hong Kong study, “It remains possible that other viruses act as opportunistic secondary invaders to enhance the disease progression.” Viral, bacterial, or fungal organisms may also help increase the efficiency of SARS’ transmission. Organisms that have been suggested as possible cofactors include human metapneumovirus and Chlamydia pneumoniae.

—Ellen Rosen