In 2003, a study was conducted on six patients who died from severe acute respiratory syndrome (SARS) to investigate the lung pathology associated with the disease. The study aimed to understand the pathogenesis of SARS and its relationship to current therapies. The patients were selected based on a modified WHO case definition of SARS, and all underwent post-mortem examinations or lung biopsies. Only one patient had a full autopsy, while the others had limited post-mortem examinations. The study included virological and pathological investigations, including reverse-transcriptase PCR, serology, and immunohistochemistry. All six patients had serological evidence of recent infection with the SARS-associated coronavirus (SARS-CoV). The pathological findings included diffuse alveolar damage, bronchial epithelial denudation, loss of cilia, squamous metaplasia, and giant-cell infiltrates. Secondary bacterial pneumonia was present in one case, and haemophagocytosis was observed in two patients. The alveolar pneumocytes showed cytomegaly with granular amphophilic cytoplasm. Electron microscopy revealed viral particles in the cytoplasm of epithelial cells corresponding to coronavirus. The study found that 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. The study also found that SARS-CoV infection in the early stages seems to stimulate epithelial cells and results in cellular proliferation and squamous metaplasia in the lung. Macrophage proliferation is more prominent in the consolidated areas of the lung. The findings of haemophagocytosis in the lung and white-pulp atrophy of the spleen identified in SARS are reminiscent of those reported in fatal influenza subtype H5N1 disease in 1997. Haemophagocytosis has been attributed to cytokine dysregulation. Lymphopenia is another feature common to both SARS-CoV and H5N1 influenza pneumonia. The study highlights the importance of understanding the pathogenesis of SARS and its relationship to current therapies. The findings suggest that proinflammatory cytokines released by stimulated macrophages in the alveoli have a prominent role in the pathogenesis of SARS, resulting in cytokine dysregulation. This has implications for the management of coronavirus pneumonia. Intervention with steroids might modulate this cytokine response and prevent a fatal outcome. The study also emphasizes the need for a more promising antiviral agent in the treatment of this disease. The results of this study contribute to the understanding of SARS and its pathology, and highlight the importance of continued research in this area.In 2003, a study was conducted on six patients who died from severe acute respiratory syndrome (SARS) to investigate the lung pathology associated with the disease. The study aimed to understand the pathogenesis of SARS and its relationship to current therapies. The patients were selected based on a modified WHO case definition of SARS, and all underwent post-mortem examinations or lung biopsies. Only one patient had a full autopsy, while the others had limited post-mortem examinations. The study included virological and pathological investigations, including reverse-transcriptase PCR, serology, and immunohistochemistry. All six patients had serological evidence of recent infection with the SARS-associated coronavirus (SARS-CoV). The pathological findings included diffuse alveolar damage, bronchial epithelial denudation, loss of cilia, squamous metaplasia, and giant-cell infiltrates. Secondary bacterial pneumonia was present in one case, and haemophagocytosis was observed in two patients. The alveolar pneumocytes showed cytomegaly with granular amphophilic cytoplasm. Electron microscopy revealed viral particles in the cytoplasm of epithelial cells corresponding to coronavirus. The study found that 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. The study also found that SARS-CoV infection in the early stages seems to stimulate epithelial cells and results in cellular proliferation and squamous metaplasia in the lung. Macrophage proliferation is more prominent in the consolidated areas of the lung. The findings of haemophagocytosis in the lung and white-pulp atrophy of the spleen identified in SARS are reminiscent of those reported in fatal influenza subtype H5N1 disease in 1997. Haemophagocytosis has been attributed to cytokine dysregulation. Lymphopenia is another feature common to both SARS-CoV and H5N1 influenza pneumonia. The study highlights the importance of understanding the pathogenesis of SARS and its relationship to current therapies. The findings suggest that proinflammatory cytokines released by stimulated macrophages in the alveoli have a prominent role in the pathogenesis of SARS, resulting in cytokine dysregulation. This has implications for the management of coronavirus pneumonia. Intervention with steroids might modulate this cytokine response and prevent a fatal outcome. The study also emphasizes the need for a more promising antiviral agent in the treatment of this disease. The results of this study contribute to the understanding of SARS and its pathology, and highlight the importance of continued research in this area.