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Case Reports
. 2003 May 24;361(9371):1773-8.
doi: 10.1016/s0140-6736(03)13413-7.

Lung pathology of fatal severe acute respiratory syndrome

John M Nicholls  1 , Leo L M Poon, Kam C Lee, Wai F Ng, Sik T Lai, Chung Y Leung, Chung M Chu, Pak K Hui, Kong L Mak, Wilina Lim, Kin W Yan, Kwok H Chan, Ngai C Tsang, Yi Guan, Kwok Y Yuen, J S Malik Peiris
Affiliations
Case Reports

Lung pathology of fatal severe acute respiratory syndrome

John M Nicholls et al. Lancet. .

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.

Findings: 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.

Interpretation: 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.

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Figures

Figure 1
Figure 1
Open lung biopsy from patient 4 Arrow shows an enlarged pneumocyte with amphophilic granular cytoplasm and prominent nucleolus. Haematoxylin and eosin; ×400.
Figure 2
Figure 2
SARS showing hyaline-membrane formation and pneumocyte desquamation with focal giant-cell formation Haematoxylin and eosin; ×400.
Figure 3
Figure 3
SARS-CoV pneumonia with cytomegaly of pneumocytes Haematoxylin and eosin; ×400.
Figure 4
Figure 4
CD68 macrophage antibody staining of giant cells in patient 5 Diaminobenzidine with haematoxylin counterstain; ×400.
Figure 5
Figure 5
Squamous metaplasia of bronchial mucosa in SARS-CoV pneumonia Haematoxylin and eosin; ×400.
Figure 6
Figure 6
Septal inflammation of patient 2 A: Increased numbers of mononuclear cells with haemophagocytosis. Haematoxylin and eosin; ×400. B: The mononuclear cells are CD68 positive. Diaminobenzidine with haematoxylin counterstain.
Figure 7
Figure 7
Thin-section electron micrograph showing a dilated secretory vesicle containing a 90 nm coronavirus particle ×63 000.
See this image and copyright information in PMC

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