Multiple organ infection and the pathogenesis of SARS

Gu, Jiang; Gong, Encong; Zhang, Bo; Zheng, Jie; Gao, Zifen; Zhong, Yanfeng; Zou, Wanzhong; Zhan, Jun; Wang, Shenglan; Xie, Zhigang; Zhuang, Hui; Wu, Bingquan; Zhong, Haohao; Shao, Hongquan; Fang, Weigang; Gao, Dongshia; Pei, Fei; Li, Xingwang; He, Zhongpin; Xu, Danzhen; Shi, Xeying; Anderson, Virginia M.; Leong, Anthony S.-Y.

The spleen and lymph nodes were atrophic (Fig. 2 L) . The average weight of the spleen was 62% of that of controls and unconfirmed cases. LM with hematoxylin and eosin staining revealed a notable decrease of lymphocytes in these organs (Fig. 2 C) . Immunolabeling with seven markers was undertaken to identify seven cell types (Table III) . All immune cell types, including dendritic cells, were decreased significantly (P Ͻ 0.01), and CD68 positive macrophages, which were decreased in number, were noticeably (P Ͻ 0.01) increased in size and gave the impression of macrophage activation ( Fig. 2 , D and E). In the negative control for immunohistochemistry of spleens from confirmed SARS patients in which PBS was substituted for the anti-CD68 antibody, no positive signal was detected ( Fig. 2 F) . In situ hybridization identified the SARS viral sequence in the enlarged macrophages and in the isolated and sometimes clustered T lymphocytes, which were distributed mostly at the periphery of the germinal centers of the splenic white pulp, lymph nodes, and peripheral blood (Fig. 1 E; Fig. 2 G, H, J, and M). The lymphoid component of the intestine showed widespread degenerative changes. The lymphoid follicles (Peyer's patches) showed markedly decreased lymphocytes (Fig. 3 A) , and in severe cases only the depleted stromal framework of the structure remained. EM detected viral particles in the submucosa of the gut (Fig. 3 , B and C) and within the residual lymphocytes. In situ hybridization demonstrated the presence of SARS positivity in the lymphocytes of the mucosa and the submucosa (Fig. 3 D) . Positive signal was not found in the negative control, in which no specific probe were used, or in the non-SARS cases (Fig. 3 , E and F).