This Date in UCSF History: Solving SARS

Sunday, April 19, 2020

Originally published in Synapse on April 17, 2003. An international team of investigators, including UCSF’s Joseph DeRisi and researchers at the Centers for Disease Control and Prevention in Atlanta, have identified a novel coronavirus as the probable cause of SARS, or severe acute respiratory syndrome.

Their work demonstrates the power of classical epidemiological and laboratory methods, enhanced by newer molecular genetic techniques and rapid global communication, to identify new pathogens with unprecedented speed.

This achievement has already led to specific tests for diagnosis of SARS and may soon enable the development of a vaccine or antiviral therapy.

The SARS epidemic began late last year in southern China, with reports of life-threatening respiratory illness unassociated with any known pathogen.

The signs and symptoms are nonspecific, and may include fever, chills, cough, shortness of breath, headache, and muscle aches.

The disease spread rapidly during February and March of this year; as of April 8, over 2600 cases had been diagnosed in 20 countries, including the United States. A total of 103 deaths had been ascribed to SARS as by the same date.

The highly contagious and potentially lethal nature of SARS made it imperative to identify the causative pathogen.

The CDC-led team began by inoculating cultured mammalian cells with material collected from the respiratory tracts of patients with SARS. One line of these cells showed visible damage — called a cytopathic effect — that quickly spread throughout the culture and could be transferred to fresh cultures, suggesting that it was caused by an infectious organism.

The damaged cells were examined by electron microscopy, revealing abundant viral particles. Comparison of their EM appearance to that of known pathogens suggested that they might belong to the family of coronaviruses, previously known only to cause mild respiratory infections in humans.

Several coronaviruses are, however, known to cause more severe illness in domestic animals. Gene sequences were amplified from the cultured virus by the polymerase chain reaction (PCR), using sequence information from known coronaviruses as a starting point.

The amplified sequences confirmed that the SARS-associated virus is a novel coronavirus, only-distantly related to other members of the family.

These sequences were identical in all isolates of the coronavirus from different patients, consistent with a single source for the outbreak.

Further testing showed that the new coronavirus could be seen by electron microscopy in fluid from the lungs of some SARS patients, and that many recovering patients have developed antibodies against the newly identified coronavirus.

These antibodies could not be found in a large randomly selected sample of American blood donors, suggesting that the U.S. population has not previously been exposed to this coronavirus.

The team’s inability to demonstrate the specific antibodies in some patients diagnosed with SARS raises the possibility that these patients were misdiagnosed, given the nonspecific clinical diagnostic criteria.

Ongoing work based on the identification of the SARS-associated coronavirus includes the improvement of diagnostic techniques, investigation of potential vaccines, and screening of known and investigational antiviral compounds for activity against the new virus.

It is too early to tell how far the epidemic will spread. However, the identification of the probable causative pathogen is a major step forward in our fight against this new disease.

The CDC group’s report, a similar paper from a European team that independently identified the coronavirus, and related reports are available on the New England Journal of Medicine Web site.