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      Multiple organ infection and the pathogenesis of SARS

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          Abstract

          After >8,000 infections and >700 deaths worldwide, the pathogenesis of the new infectious disease, severe acute respiratory syndrome (SARS), remains poorly understood. We investigated 18 autopsies of patients who had suspected SARS; 8 cases were confirmed as SARS. We evaluated white blood cells from 22 confirmed SARS patients at various stages of the disease. T lymphocyte counts in 65 confirmed and 35 misdiagnosed SARS cases also were analyzed retrospectively. SARS viral particles and genomic sequence were detected in a large number of circulating lymphocytes, monocytes, and lymphoid tissues, as well as in the epithelial cells of the respiratory tract, the mucosa of the intestine, the epithelium of the renal distal tubules, the neurons of the brain, and macrophages in different organs. SARS virus seemed to be capable of infecting multiple cell types in several organs; immune cells and pulmonary epithelium were identified as the main sites of injury. A comprehensive theory of pathogenesis is proposed for SARS with immune and lung damage as key features.

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          Coronavirus as a possible cause of severe acute respiratory syndrome.

          V Cheng, A. Yung, J. S. Malik Peiris … (2003)
          An outbreak of severe acute respiratory syndrome (SARS) has been reported in Hong Kong. We investigated the viral cause and clinical presentation among 50 patients. We analysed case notes and microbiological findings for 50 patients with SARS, representing more than five separate epidemiologically linked transmission clusters. We defined the clinical presentation and risk factors associated with severe disease and investigated the causal agents by chest radiography and laboratory testing of nasopharyngeal aspirates and sera samples. We compared the laboratory findings with those submitted for microbiological investigation of other diseases from patients whose identity was masked. Patients' age ranged from 23 to 74 years. Fever, chills, myalgia, and cough were the most frequent complaints. When compared with chest radiographic changes, respiratory symptoms and auscultatory findings were disproportionally mild. Patients who were household contacts of other infected people and had older age, lymphopenia, and liver dysfunction were associated with severe disease. A virus belonging to the family Coronaviridae was isolated from two patients. By use of serological and reverse-transcriptase PCR specific for this virus, 45 of 50 patients with SARS, but no controls, had evidence of infection with this virus. A coronavirus was isolated from patients with SARS that might be the primary agent associated with this disease. Serological and molecular tests specific for the virus permitted a definitive laboratory diagnosis to be made and allowed further investigation to define whether other cofactors play a part in disease progression.
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            Enteric involvement of severe acute respiratory syndrome-associated coronavirus infection 1

            Wai Leung, Ka-fai To, Paul K.S. Chan … (2003)
            Background & Aims: Severe acute respiratory syndrome (SARS) is a recently emerged infection from a novel coronavirus (CoV). Apart from fever and respiratory complications, gastrointestinal symptoms are frequently observed in patients with SARS but the significance remains undetermined. Herein, we describe the clinical, pathologic, and virologic features of the intestinal involvement of this new viral infection. Methods: A retrospective analysis of the gastrointestinal symptoms and other clinical parameters of the first 138 patients with confirmed SARS admitted for a major outbreak in Hong Kong in March 2003 was performed. Intestinal specimens were obtained by colonoscopy or postmortem examination to detect the presence of coronavirus by electron microscopy, virus culture, and reverse-transcription polymerase chain reaction. Results: Among these 138 patients with SARS, 28 (20.3%) presented with watery diarrhea and up to 38.4% of patients had symptoms of diarrhea during the course of illness. Diarrhea was more frequently observed during the first week of illness. The mean number of days with diarrhea was 3.7 ± 2.7, and most diarrhea was self-limiting. Intestinal biopsy specimens obtained by colonoscopy or autopsy showed minimal architectural disruption but the presence of active viral replication within both the small and large intestine. Coronavirus was also isolated by culture from these specimens, and SARS-CoV RNA can be detected in the stool of patients for more than 10 weeks after symptom onset. Conclusions: Diarrhea is a common presenting symptom of SARS. The intestinal tropism of the SARS-CoV has major implications on clinical presentation and viral transmission.
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              Clinical presentations and outcome of severe acute respiratory syndrome in children

              KLE Hon, CW Leung, WTF Cheng … (2003)
              Summary Hong Kong has been severely affected by severe acute respiratory syndrome (SARS). Contact in households and healthcare settings is thought to be important for transmission, putting children at particular risk. Most data so far, however, have been for adults. We prospectively followed up the first ten children with SARS managed during the early phase of the epidemic in Hong Kong. All the children had been in close contact with infected adults. Persistent fever, cough, progressive radiographic changes of chest and lymphopenia were noted in all patients. The children were treated with high-dose ribavirin, oral prednisolone, or intravenous methylprednisolone, with no short-term adverse effects. Four teenagers required oxygen therapy and two needed assisted ventilation. None of the younger children required oxygen supplementation. Compared with adults and teenagers, SARS seems to have a less aggressive clinical course in younger children.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Exp Med
                Title: The Journal of Experimental Medicine
                Publisher: The Rockefeller University Press
                ISSN (Print): 0022-1007
                ISSN (Electronic): 1540-9538
                Publication date (Print): 1 August 2005
                Volume: 202
                Issue: 3
                Pages: 415-424
                Affiliations
                [1 ]Department of Pathology, Peking University, Beijing, China 100083
                [2 ]Department of Microbiology, Peking University, Beijing, China 100083
                [3 ]Beijing Ditan Hospital, Beijing, China 100011
                [4 ]State University of New York Health Science Center at Brooklyn, Brooklyn, NY 11203
                [5 ]Hunter Area Pathology Services and Discipline of Anatomical Pathology, University of Newcastle, Newcastle, Australia 2310
                Author notes

                CORRESPONDENCE Jiang Gu: jgu@ 123456privatedoctor.org

                Article
                Publisher ID: 20050828
                DOI: 10.1084/jem.20050828
                PMC ID: 2213088
                PubMed ID: 16043521
                SO-VID: 5c19cd54-988b-40bc-9bcb-0f3f4e138449
                Copyright © Copyright © 2005, The Rockefeller University Press
                History
                Date received : 25 April 2005
                Date accepted : 16 June 2005
                Categories
                Subject: Article

                ScienceOpen disciplines: Medicine
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                ScienceOpen disciplines: Medicine

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