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      A Novel Coronavirus Associated with Severe Acute Respiratory Syndrome

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          Abstract

          A worldwide outbreak of severe acute respiratory syndrome (SARS) has been associated with exposures originating from a single ill health care worker from Guangdong Province, China. We conducted studies to identify the etiologic agent of this outbreak. We received clinical specimens from patients in seven countries and tested them, using virus-isolation techniques, electron-microscopical and histologic studies, and molecular and serologic assays, in an attempt to identify a wide range of potential pathogens. None of the previously described respiratory pathogens were consistently identified. However, a novel coronavirus was isolated from patients who met the case definition of SARS. Cytopathological features were noted in Vero E6 cells inoculated with a throat-swab specimen. Electron-microscopical examination revealed ultrastructural features characteristic of coronaviruses. Immunohistochemical and immunofluorescence staining revealed reactivity with group I coronavirus polyclonal antibodies. Consensus coronavirus primers designed to amplify a fragment of the polymerase gene by reverse transcription-polymerase chain reaction (RT-PCR) were used to obtain a sequence that clearly identified the isolate as a unique coronavirus only distantly related to previously sequenced coronaviruses. With specific diagnostic RT-PCR primers we identified several identical nucleotide sequences in 12 patients from several locations, a finding consistent with a point-source outbreak. Indirect fluorescence antibody tests and enzyme-linked immunosorbent assays made with the new isolate have been used to demonstrate a virus-specific serologic response. This virus may never before have circulated in the U.S. population. A novel coronavirus is associated with this outbreak, and the evidence indicates that this virus has an etiologic role in SARS. Because of the death of Dr. Carlo Urbani, we propose that our first isolate be named the Urbani strain of SARS-associated coronavirus. Copyright 2003 Massachusetts Medical Society

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          Most cited references 20

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          Identification of severe acute respiratory syndrome in Canada.

          Severe acute respiratory syndrome (SARS) is a condition of unknown cause that has recently been recognized in patients in Asia, North America, and Europe. This report summarizes the initial epidemiologic findings, clinical description, and diagnostic findings that followed the identification of SARS in Canada. SARS was first identified in Canada in early March 2003. We collected epidemiologic, clinical, and diagnostic data from each of the first 10 cases prospectively as they were identified. Specimens from all cases were sent to local, provincial, national, and international laboratories for studies to identify an etiologic agent. The patients ranged from 24 to 78 years old; 60 percent were men. Transmission occurred only after close contact. The most common presenting symptoms were fever (in 100 percent of cases) and malaise (in 70 percent), followed by nonproductive cough (in 100 percent) and dyspnea (in 80 percent) associated with infiltrates on chest radiography (in 100 percent). Lymphopenia (in 89 percent of those for whom data were available), elevated lactate dehydrogenase levels (in 80 percent), elevated aspartate aminotransferase levels (in 78 percent), and elevated creatinine kinase levels (in 56 percent) were common. Empirical therapy most commonly included antibiotics, oseltamivir, and intravenous ribavirin. Mechanical ventilation was required in five patients. Three patients died, and five have had clinical improvement. The results of laboratory investigations were negative or not clinically significant except for the amplification of human metapneumovirus from respiratory specimens from five of nine patients and the isolation and amplification of a novel coronavirus from five of nine patients. In four cases both pathogens were isolated. SARS is a condition associated with substantial morbidity and mortality. It appears to be of viral origin, with patterns suggesting droplet or contact transmission. The role of human metapneumovirus, a novel coronavirus, or both requires further investigation. Copyright 2003 Massachusetts Medical Society
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            Human metapneumovirus infections in young and elderly adults.

            Human metapneumovirus virus (hMPV) is a newly discovered respiratory pathogen with limited epidemiological data available. Cohorts of young and older adults were prospectively evaluated for hMPV infection during 2 winter seasons. Patients hospitalized for cardiopulmonary conditions during that period were also studied. Overall, 44 (4.5%) of 984 illnesses were associated with hMPV infection, and 9 (4.1%) of 217 asymptomatic subjects were infected. There was a significant difference in rates of hMPV illnesses between years 1 and 2 (7/452 [1.5%] vs. 37/532 [7.0%]; P<.0001). In the second year, 11% of hospitalized patients had evidence of hMPV infection. Infections occurred in all age groups but were most common among young adults. Frail elderly people with hMPV infection frequently sought medical attention. In conclusion, hMPV infection occurs in adults of all ages and may account for a significant portion of persons hospitalized with respiratory infections during some years.
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              A morbillivirus that caused fatal disease in horses and humans.

              A morbillivirus has been isolated and added to an increasing list of emerging viral diseases. This virus caused an outbreak of fatal respiratory disease in horses and humans. Genetic analyses show it to be only distantly related to the classic morbilliviruses rinderpest, measles, and canine distemper. When seen by electron microscopy, viruses had 10- and 18-nanometer surface projections that gave them a "double-fringed" appearance. The virus induced syncytia that developed in the endothelium of blood vessels, particularly the lungs.
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                Author and article information

                Journal
                New England Journal of Medicine
                N Engl J Med
                Massachusetts Medical Society
                0028-4793
                1533-4406
                May 15 2003
                May 15 2003
                : 348
                : 20
                : 1953-1966
                Article
                10.1056/NEJMoa030781
                12690092
                © 2003
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