Lung pathology of fatal severe acute respiratory syndrome.
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.
Nicholls
John M
JM
Department of Pathology, University of Hong Kong, Hong Kong Special Administrative Region, China.
Poon
Leo L M
LL
Lee
Kam C
KC
Ng
Wai F
WF
Lai
Sik T
ST
Leung
Chung Y
CY
Chu
Chung M
CM
Hui
Pak K
PK
Mak
Kong L
KL
Lim
Wilina
W
Yan
Kin W
KW
Chan
Kwok H
KH
Tsang
Ngai C
NC
Guan
Yi
Y
Yuen
Kwok Y
KY
Peiris
J S Malik
JS
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