[Lung pathology and pathogenesis of severe acute respiratory syndrome: a report of six full autopsies].
OBJECTIVE
Severe acute respiratory syndrome (SARS) is an emerging infectious disease that first manifested in humans in November 2002. The SARS-associated coronavirus (SARS-CoV) has been identified as the causal agent, but the pathology and pathogenesis are still not quite clear.


METHODS
Post-mortem lung samples from six patients who died from SARS from April to July 2003 were studied by light and electron microscopy, Masson trichromal staining and immunohistochemistry. Evidence of infection with the SARS-CoV was determined by reverse-transcription PCR (RT-PCR) , serological examination and electron microscopy.


RESULTS
Four of six patients had serological and RT-PCR evidence of recent infection of SARS-CoV. Morphologic changes are summarized as follows: (1) Diffuse and bilateral lung consolidation was seen in all patients (6/6) with increasing lung weight. (2) Diffuse alveolar damage was universal (6/6) with hyaline membrane formation (6/6), intra-alveolar edema/hemorrhage (6/6), fibrin deposition (6/6), pneumocyte desquamation (6/6). A marked disruption in the integrity of the alveolar epithelium was confirmed by immunostaining for the epithelial marker AE1/AE3 (6/6). (3) Type II pneumocytes, with mild hyperplasia, atypia, cytomegaly with granular amphophilic cytoplasm and intracytoplasmic lipid accumulation (5/6). (4) Giant cells in the alveoli were seen in five of 6 patients (5/6) , most of which were positive for the epithelial marker AE1/AE3 (5/6), but some cells were positive for the macrophage marker CD68(2/6). (5) A pronounced increase of macrophages were seen in the alveoli and the interstitium of the lung (6/6), which was confirmed by histological study and immunohistochemistry. (6) Haemophagocytosis was present in five of the 6 patients(5/6). (7) Lung fibrosis was seen in five patients(5/6), with alveolar septa and interstitium thickening(5/6), intraalveolar organizing exudates (6/6) and pleura thickening (4/6). Proliferation of collagen was confirmed by Masson trichromal staining, most of which was type III collagen by immunostaining. The formation of distinctive fibroblast/myofibroblast foci was seen in five patients (5/6) by light microscopy and immunochemistry. (8) Squamous metaplasia of bronchial mucosa was seen in five patients(5/6). (9) Thrombi was seen in all patients(6/6). (10) Accompanying infection was present in two patients, one was bacteria, the other was fungus. In addition, electron microscopy revealed viral particles in the cytoplasm of alveolar epithelial cells and endothelial cells corresponding to coronavirus.


CONCLUSIONS
Direct injury of SARS-CoV on alveolar epithelium, prominent macrophage infiltration and distinctive fibroblast/myofibroblast proliferation may play major roles in the pathogenesis of SARS.
Department of Pathology, Peking University Health Science Center, Beijing, China.
Fei
F
Pei
Jie
J
Zheng
Zi-fen
ZF
Gao
Yan-feng
YF
Zhong
Wei-gang
WG
Fang
En-cong
EC
Gong
Wan-zhong
WZ
Zou
Sheng-lan
SL
Wang
Dong-xia
DX
Gao
Zhi-gang
ZG
Xie
Min
M
Lu
Xue-ying
XY
Shi
Cong-rong
CR
Liu
Jing-ping
JP
Yang
Yu-ping
YP
Wang
Zhi-hui
ZH
Han
Xiao-hong
XH
Shi
Wen-bin
WB
Dao
Jiang
J
Gu
D000328:Adult; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D004848:Epithelium / Q000473:pathology; D005260:Female; D006801:Humans; D007633:Keratins / Q000276:immunology; D008168:Lung / Q000473:pathology* / Q000648:ultrastructure / Q000821:virology; D008297:Male; D008875:Middle Aged; D011650:Pulmonary Alveoli / Q000473:pathology; D011658:Pulmonary Fibrosis / Q000209:etiology / Q000473:pathology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000302:isolation & purification*; D045169:Severe Acute Respiratory Syndrome / Q000150:complications / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D000097382:CD68 Molecule
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D007633:Keratins; C067980:CD68 antigen, human; D000097382:CD68 Molecule