title: Lung pathology of fatal severe acute respiratory syndrome.
abstract: BACKGROUND
  Severe acute respiratory syndrome (SARS) is a novel infectious disease with global impact. A virus from the family Coronaviridae has been identified as the cause, but the pathogenesis is still unclear.
  
  
  METHODS
  Post-mortem tissue samples from six patients who died from SARS in February and March, 2003, and an open lung biopsy from one of these patients were studied by histology and virology. Only one full autopsy was done. Evidence of infection with the SARS-associated coronavirus (SARS-CoV) and human metapneumovirus was sought by reverse-transcriptase PCR and serology. Pathological samples were examined by light and electron microscopy and immunohistochemistry.
  
  
  RESULTS
  All six patients had serological evidence of recent infection with SARS-CoV. Diffuse alveolar damage was common but not universal. Morphological changes identified were bronchial epithelial denudation, loss of cilia, and squamous metaplasia. Secondary bacterial pneumonia was present in one case. A giant-cell infiltrate was seen in four patients, with a pronounced increase in macrophages in the alveoli and the interstitium of the lung. Haemophagocytosis was present in two patients. The alveolar pneumocytes also showed cytomegaly with granular amphophilic cytoplasm. The patient for whom full autopsy was done had atrophy of the white pulp of the spleen. Electron microscopy revealed viral particles in the cytoplasm of epithelial cells corresponding to coronavirus.
  
  
  CONCLUSIONS
  SARS is associated with epithelial-cell proliferation and an increase in macrophages in the lung. The presence of haemophagocytosis supports the contention that cytokine dysregulation may account, at least partly, for the severity of the clinical disease. The case definition of SARS should acknowledge the range of lung pathology associated with this disease.
authors.affiliation: Department of Pathology, University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: John M
authors.initials: JM
authors.lastname: Nicholls
authors.forename: Leo L M
authors.initials: LL
authors.lastname: Poon
authors.forename: Kam C
authors.initials: KC
authors.lastname: Lee
authors.forename: Wai F
authors.initials: WF
authors.lastname: Ng
authors.forename: Sik T
authors.initials: ST
authors.lastname: Lai
authors.forename: Chung Y
authors.initials: CY
authors.lastname: Leung
authors.forename: Chung M
authors.initials: CM
authors.lastname: Chu
authors.forename: Pak K
authors.initials: PK
authors.lastname: Hui
authors.forename: Kong L
authors.initials: KL
authors.lastname: Mak
authors.forename: Wilina
authors.initials: W
authors.lastname: Lim
authors.forename: Kin W
authors.initials: KW
authors.lastname: Yan
authors.forename: Kwok H
authors.initials: KH
authors.lastname: Chan
authors.forename: Ngai C
authors.initials: NC
authors.lastname: Tsang
authors.forename: Yi
authors.initials: Y
authors.lastname: Guan
authors.forename: Kwok Y
authors.initials: KY
authors.lastname: Yuen
authors.forename: J S Malik
authors.initials: JS
authors.lastname: Peiris
mesh_terms: D000328:Adult; D001706:Biopsy; D001980:Bronchi / Q000473:pathology; D002467:Cell Nucleus / Q000648:ultrastructure; D017809:Fatal Outcome; D005260:Female; D015726:Giant Cells / Q000648:ultrastructure; D006801:Humans; D008168:Lung / Q000473:pathology* / Q000821:virology; D008297:Male; D008679:Metaplasia; D008875:Middle Aged; D009929:Organ Size; D045473:Severe acute respiratory syndrome-related coronavirus / Q000302:isolation & purification; D045169:Severe Acute Respiratory Syndrome / Q000150:complications / Q000473:pathology* / Q000821:virology