Microbiology and Infectious Disease / SARS VIRUS INFECTS PNEUMOCYTES

Previous reports have indicated that patients with severe acute respiratory syndrome (SARS)–associated coronavirus infection could develop atypical pneumonia with fulminant pulmonary edema. However, the target cells of SARS viral infection have not been characterized in detail. We report the pathologic findings of the lung in 3 cases of SARS. Chest radiographs at 2 to 3 weeks of infection revealed an atypical pneumonia with pulmonary consolidation, a clinical characteristic of SARS infection. The presence of the SARS virus was determined by nested reverse transcription–polymerase chain reaction (RT-PCR), and the infected cells were identified by in situ hybridization in open-lung biopsy and postmortem necropsy specimens. Expression of SARS virus–encoded RNA was detected in all 3 cases by RT-PCR, and the SARS viral signal was localized in pneumocytes by using in situ hybridization. Severe acute respiratory syndrome (SARS) is an acute infectious disease that affects primarily the lower respiratory tract, with clinical manifestations of atypical pneumonia with dry cough, persistent fever, progressive dyspnea, and, sometimes, the abrupt deterioration of lung function1-5 and the ensuing oxygen deprivation–associated systemic organ failures.6,7 At this stage, the disease can be lethal. Postmortem pathologic examination showed that fulminant pulmonary interstitial infiltrate, substantial pulmonary edema, and extensive pulmonary consolidation with alveolitis, formation of hyaline membrane, and the presence of desquamated alveolar epithelial cells, which corresponded well with the progression of clinical symptoms, frequently were observed.4,7 An elegant study by Ksiazek et al4 further demonstrated that in addition to the dispersed alveolar epithelial cells, foamy macrophages and multinucleated giant cells were abundant in the damaged alveolus as well. Inoculation with bronchoalveolar lavage fluid from these patients can induce not only cytopathic changes of Vero E6 cells, but also formation of multinucleated syncytial cells, an index of viral infection. The subsequent analysis of extracellular particles from the supernatant of cytopathically altered Vero E6 cells by negative-stain electron microscopy revealed the characteristic coronavirus particle.4 However, the results of nucleotide sequence alignment indicated that these isolates were quite different from any known coronavirus,1-5 a positive singlestranded RNA virus.8 Because the virus is SARS infection–specific, it was named SARS-associated coronavirus, or SARS virus. Nevertheless, the target cells of SARS viral infection and the essence of multinucleated giant cells are not well characterized. Microbiology and Infectious Disease / ORIGINAL ARTICLE Am J Clin Pathol 2004;121:574-580 575 575 DOI: 10.1309/C0EDU0RAQBTXBHCE 575 © American Society for Clinical Pathology In the present study, we used nested reverse transcription–polymerase chain reaction (RT-PCR) for the immediate determination of SARS viral infection, and the presence of the SARS viral signal was identified by using in situ hybridization. Materials and Methods