[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.
Pei
Fei
F
Department of Pathology, Peking University Health Science Center, Beijing, China.
Zheng
Jie
J
Gao
Zi-fen
ZF
Zhong
Yan-feng
YF
Fang
Wei-gang
WG
Gong
En-cong
EC
Zou
Wan-zhong
WZ
Wang
Sheng-lan
SL
Gao
Dong-xia
DX
Xie
Zhi-gang
ZG
Lu
Min
M
Shi
Xue-ying
XY
Liu
Cong-rong
CR
Yang
Jing-ping
JP
Wang
Yu-ping
YP
Han
Zhi-hui
ZH
Shi
Xiao-hong
XH
Dao
Wen-bin
WB
Gu
Jiang
J
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