Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome

Lancet. 2003 Jul 26;362(9380):263-70. doi: 10.1016/S0140-6736(03)13967-0.

Abstract

Background: The worldwide outbreak of severe acute respiratory syndrome (SARS) is associated with a newly discovered coronavirus, SARS-associated coronavirus (SARS-CoV). We did clinical and experimental studies to assess the role of this virus in the cause of SARS.

Methods: We tested clinical and postmortem samples from 436 SARS patients in six countries for infection with SARS-CoV, human metapneumovirus, and other respiratory pathogens. We infected four cynomolgus macaques (Macaca fascicularis) with SARS-CoV in an attempt to replicate SARS and did necropsies on day 6 after infection.

Findings: SARS-CoV infection was diagnosed in 329 (75%) of 436 patients fitting the case definition of SARS; human metapneumovirus was diagnosed in 41 (12%) of 335, and other respiratory pathogens were diagnosed only sporadically. SARS-CoV was, therefore, the most likely causal agent of SARS. The four SARS-CoV-infected macaques excreted SARS-CoV from nose, mouth, and pharynx from 2 days after infection. Three of four macaques developed diffuse alveolar damage, similar to that in SARS patients, and characterised by epithelial necrosis, serosanguineous exudate, formation of hyaline membranes, type 2 pneumocyte hyperplasia, and the presence of syncytia. SARS-CoV was detected in pneumonic areas by virus isolation and RT-PCR, and was localised to alveolar epithelial cells and syncytia by immunohistochemistry and transmission electron microscopy.

Interpretation: Replication in SARS-CoV-infected macaques of pneumonia similar to that in human beings with SARS, combined with the high prevalence of SARS-CoV infection in SARS patients, fulfill the criteria required to prove that SARS-CoV is the primary cause of SARS.

MeSH terms

  • Animals
  • China / epidemiology
  • Communicable Diseases, Emerging / epidemiology
  • Communicable Diseases, Emerging / virology
  • Disease Models, Animal
  • Disease Outbreaks
  • Global Health
  • Humans
  • Macaca fascicularis
  • Pulmonary Alveoli / pathology
  • Pulmonary Alveoli / virology
  • SARS Virus / isolation & purification*
  • SARS Virus / pathogenicity
  • Severe Acute Respiratory Syndrome / epidemiology
  • Severe Acute Respiratory Syndrome / pathology
  • Severe Acute Respiratory Syndrome / virology*