Immunohistochemical study of severe acute respiratory syndrome-associated coronavirus in tissue sections of patients.

BACKGROUND AND PURPOSE: Severe acute respiratory syndrome (SARS) is a life-threatening and highly contagious disease caused by the novel SARS coronavirus (SARS-CoV). Immunohistochemical staining for SARS-CoV in the tissue sections of SARS patients is helpful in investigations of the biologic behavior of this virus in human tissue, and to determine the target cells of this virus in different organs.

METHODS: We studied the pathologic specimens from 6 SARS patients by immunohistochemical staining using a specific antibody against SARS-CoV.

RESULTS: Positive viral staining was only found in the lung tissue taken from the patients who died in the early stage of the disease, usually less than 10 days after symptom onset. No positive staining was found in the lung tissue specimens collected in the mid-to-late stage of the disease. The SARS-CoV-infected cells had a patchy distribution and tended to be present in the periphery of the lung. Immunohistochemically, these viral-infected cells were located mainly along the alveolar space, had a cuboidal appearance, and were reactive to cytokeratin and surfactant protein C. This suggested that type II pneumocytes are the main target cell of SARS-CoV in the lung. Occasional intra-alveolar macrophages were also weakly reactive to SARS-CoV antibody. In addition to the lung, positive viral staining was also found in the mucosal epithelium of the large intestine in another patient who had the clinical symptom of diarrhea. No evidence of viral staining was found in other organs including kidney, liver, lymph node and spleen. The skeletal muscle specimens of 2 patients who had rhabdomyolysis were also negative for SARS-CoV.

CONCLUSIONS: SARS-CoV is mainly present in the cytoplasm of type II pneumocytes and can only be detected in the lung tissue during the early stage of the disease. In the patient who had symptoms of diarrhea, SARS-CoV staining was also identified in the mucosal epithelium of the colon.