A Novel Coronavirus Associated with Severe Acute Respiratory Syndrome
Thomas G. Ksiazek, D.V.M., Ph.D., Dean Erdman, Dr.P.H., Cynthia S. Goldsmith, M.S., Sherif R. Zaki, M.D., Ph.D., Teresa Peret, Ph.D., Shannon Emery, B.S., Suxiang Tong, Ph.D., Carlo Urbani, M.D., James A. Comer, Ph.D., M.P.H., Wilina Lim, M.D., Pierre E. Rollin, M.D., Scott F. Dowell, M.D., M.P.H., Ai-Ee Ling, M.D., Charles D. Humphrey, Ph.D., Wun-Ju Shieh, M.D., Ph.D., Jeannette Guarner, M.D., Christopher D. Paddock, M.D., M.P.H.T.M., Paul Rota, Ph.D., Barry Fields, Ph.D., Joseph DeRisi, Ph.D., Jyh-Yuan Yang, Ph.D., Nancy Cox, Ph.D., James M. Hughes, M.D., James W. LeDuc, Ph.D., William J. Bellini, Ph.D., Larry J. Anderson, M.D., and the SARS Working Group
Background A worldwide outbreak of severe acute respiratorysyndrome (SARS) has been associated with exposures originatingfrom a single ill health care worker from Guangdong Province,China. We conducted studies to identify the etiologic agentof this outbreak.
Methods We received clinical specimens from patients in sevencountries and tested them, using virus-isolation techniques,electron-microscopical and histologic studies, and molecularand serologic assays, in an attempt to identify a wide rangeof potential pathogens.
Results None of the previously described respiratory pathogenswere consistently identified. However, a novel coronavirus wasisolated from patients who met the case definition of SARS.Cytopathological features were noted in Vero E6 cells inoculatedwith a throat-swab specimen. Electron-microscopical examinationrevealed ultrastructural features characteristic of coronaviruses.Immunohistochemical and immunofluorescence staining revealedreactivity with group I coronavirus polyclonal antibodies. Consensuscoronavirus primers designed to amplify a fragment of the polymerasegene by reverse transcription–polymerase chain reaction(RT-PCR) were used to obtain a sequence that clearly identifiedthe isolate as a unique coronavirus only distantly related topreviously sequenced coronaviruses. With specific diagnosticRT-PCR primers we identified several identical nucleotide sequencesin 12 patients from several locations, a finding consistentwith a point-source outbreak. Indirect fluorescence antibodytests and enzyme-linked immunosorbent assays made with the newisolate have been used to demonstrate a virus-specific serologicresponse. This virus may never before have circulated in theU.S. population.
Conclusions A novel coronavirus is associated with this outbreak,and the evidence indicates that this virus has an etiologicrole in SARS. Because of the death of Dr. Carlo Urbani, we proposethat our first isolate be named the Urbani strain of SARS-associatedcoronavirus.
Source Information
From the Special Pathogens Branch (T.G.K., J.A.C., P.E.R.), Respiratory and Enteric Virus Branch (D.E., T.P., S.E., S.T., P.R., W.J.B., L.J.A.), Infectious Disease Pathology Activity (C.S.G., S.R.Z., C.D.H., W.-J.S., J.G., C.D.P.), Influenza Branch (N.C.), Division of Bacterial and Mycotic Diseases (B.F.), and Office of the Director, Division of Viral and Rickettsial Diseases (J.W.L.), and Office of the Director, National Center for Infectious Diseases (J.M.H.), National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta; the World Health Organization, Hanoi, Vietnam (C.U.); the Government Virus Unit, Queen Mary Hospital, Hong Kong, China (W.L.); the International Emerging Infectious Diseases Program, Bangkok, Thailand (S.F.D.); the Department of Pathology, Singapore General Hospital (A.-E.L.); the University of California, San Francisco (J.D.); and the Center for Disease Control, Department of Health, Taipei, Taiwan (J.-Y. Y.). This article was published at www.nejm.org on April 10, 2003.
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