SARS was first reported in China in November 2002, with over 8300 cases and 812 deaths reported by the beginning of July 2003. A novel coronavirus has been identified as the likely cause of SARS. Albert Osterhaus from Erasmus University, Rotterdam, Netherlands, and colleagues investigated the causal role of this newly discovered SARS-associated coronavirus (SARS-CoV) by analysis of the results of international investigations done by the WHO network of laboratories.
Clinical and postmortem samples were tested from 436 SARS patients in six countries for infection with SARS-CoV, human metapneumovirus, and other respiratory pathogens. As criteria for indentifying the primary cause of a disease include the production of a comparable disease in the original host or a related species, the investigators infected four macaques (Cynomolgus monkeys common in south-east Asia) with SARS-CoV. Necropsies were done on the sixth day after infection.
SARS-CoV infection was diagnosed in three-quarters of patients fitting the case definition of SARS; human metapneumovirus was diagnosed in 12% of cases and other respiratory pathogens were diagnosed only sporadically. The four SARS-CoV-infected macaques excreted SARS-CoV from nose, mouth, and pharynx from 2 days after infection.
Three of four macaques developed lung damage (diffuse alveolar damage), similar to that in SARS patients. SARS-CoV was detected in the alveolar areas of the lung by virus isolation from immunohistochemistry, transmission electron microscopy, and genetic assessment by polymerase chain reaction,.