[Morphological study of severe acute respiratory syndrome (SARS)].
ABSTRACT Seven cases of autopsy from SARS patients are studied to investigate the pathogenesis and the pathologic changes of the major organs.
Detailed gross and microscopic examination of the autopsy specimen is performed, including lung, heart, liver, kidney, spleen and lymph nodes.
All of the lungs are markedly enlarged and consolidated. Microscopically, pulmonary edema is a prominent finding, especially at the early stage of the disease (5 days after the onset). The alveolar spaces are filled with fibrinous exudates and lined with hyaline membrane. In 5 cases that undergo over 3 weeks of the course, the main pattern is organization of intra-alveolar deposit, along with fibroblastic proliferation in the alveolar septa, which leads to obliteration of alveolar space and pulmonary fibrosis. All of the lungs show bronchopneumonia, scattered hemorrhage, and proliferation of alveolar epithelial cells with desquamation. Microthrombi are seen in 6 cases. Fungal infection is noted in 2 cases. One of them is disseminative, involving bilateral lungs, heart, and kidney; the other one is diagnosed in hilar lymph nodes. In immune system, hilar and abdominal lymph nodes are usually congested and hemorrhagic, with depletion of lymphocytes, and accompanied with subcapsular sinus histiocytosis. One of the cases shows enlargement of abdominal lymph nodes, which have reduced number of germinal centers. Spleen exhibits atrophy of white pulps, and even lost of white pulps in some areas. The red pulp is markedly congested and hemorrhagic. In 5 cases, cardiomegale is prominent. Thrombosis (2 cases), focal myocarditis (1 case), and fungal myocarditis (1 case) are observed. In addition, liver shows massive necrosis (1 case) and nodular cirrhosis (1 case).
Lung is the major organ affected by SARS, demonstrated as diffuse alveolar damage. It is postulated that viral infection induces severe damage of alveolar epithelial and capillary endothelial cells, leads to pulmonary edema, intra-alveolar fibrin deposit, and hyaline membrane formation. Consequently, intra-alveolar organization and alveolar septal fibrosis causes loss of alveolar spaces, eventually, pulmonary fibrosis and atelectasis. The immune system is often affected, and presented as depletion of lymphoid tissue in lymph nodes and spleen. Secondary infection is a common complication, which should be paid close attention in the management of SARS patients.
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ABSTRACT: A new SARS animal model was established by inoculating SARS coronavirus (SARS-CoV) into rhesus macaques (Macaca mulatta) through the nasal cavity. Pathological pulmonary changes were successively detected on days 5-60 after virus inoculation. All eight animals showed a transient fever 2-3 days after inoculation. Immunological, molecular biological, and pathological studies support the establishment of this SARS animal model. Firstly, SARS-CoV-specific IgGs were detected in the sera of macaques from 11 to 60 days after inoculation. Secondly, SARS-CoV RNA could be detected in pharyngeal swab samples using nested RT-PCR in all infected animals from 5 days after virus inoculation. Finally, histopathological changes of interstitial pneumonia were found in the lungs during the 60 days after viral inoculation: these changes were less marked at later time points, indicating that an active healing process together with resolution of an acute inflammatory response was taking place in these animals. This animal model should provide insight into the mechanisms of SARS-CoV-related pulmonary disease and greatly facilitate the development of vaccines and therapeutics against SARS.The Journal of Pathology 07/2005; 206(3):251-9. DOI:10.1002/path.1769 · 7.33 Impact Factor
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ABSTRACT: Severe acute respiratory syndrome (SARS) coronavirus has been known to damage multiple organs; however, little is known about its impact on the reproductive system. In the present study, we analyzed the pathological changes of testes from six patients who died of SARS. Results suggested that SARS caused orchitis. All SARS testes displayed widespread germ cell destruction, few or no spermatozoon in the seminiferous tubule, thickened basement membrane, and leukocyte infiltration. The numbers of CD3+ T lymphocytes and CD68+ macrophages increased significantly in the interstitial tissue compared with the control group (P < 0.05). SARS viral genomic sequences were not detected in the testes by in situ hybridization. Immunohistochemistry demonstrated abundant IgG precipitation in the seminiferous epithelium of SARS testes, indicating possible immune response as the cause for the damage. Our findings indicated that orchitis is a complication of SARS. It further suggests that the reproductive functions should be followed and evaluated in recovered male SARS patients.Biology of Reproduction 02/2006; 74(2):410-6. DOI:10.1095/biolreprod.105.044776 · 3.45 Impact Factor
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ABSTRACT: During the outbreak of the emergent severe acute respiratory syndrome (SARS) infection, >30% of the approximately 8000 infected persons were health care workers. The highly infectious nature of SARS coronavirus (SARS-CoV) compelled our pathologists to consider biosafety issues in the autopsy room and for tissue processing procedures. A specially designed biosafety level 3 (BSL-3) autopsy laboratory was constructed and divided into a clean area, a semicontaminated area, a contaminated area, and 2 buffer zones. High-efficiency particulate air filters were placed in the air supply and exhaust systems. Laminar air flow was from the clean areas to the less clean areas. The negative pressures of the contaminated, semicontaminated, and clean areas were approximately -50 pa, -25 pa, and -5 pa, respectively. Personal protective equipment, including gas mask, impermeable protective clothing, and 3 layers of gloves worn during autopsies; the equipment was decontaminated before it was allowed to exit the facility. Strict BSL-3 practices were followed. When a given concentration of particulate sarin simulant was introduced into the contaminated area, it could not be detected in either the semicontaminated area or clean area, and particles >0.3 microm in size were not detected in the exhaust air. A total of 16 complete postmortem examinations for probable and suspected SARS were performed during a 2-month period. Of these, 7 reported confirmed cases of SARS. None of the 23 pathologists and technicians who participated in these autopsies was infected with SARS-CoV. Our experience suggests that BSL-3 laboratory operating principles should be among the special requirements for performing autopsies of contaminated bodies and that they can safeguard the clinicians and the environment involved in these procedures.Clinical Infectious Diseases 09/2005; 41(6):815-21. DOI:10.1086/432720 · 9.42 Impact Factor