The New England Journal of Medicine, 2003, Vol.348(20), pp.1967-1976
Background The severe acute respiratory syndrome (SARS) has recently been identified as a new clinical entity. SARS is thought to be caused by an unknown infectious agent. Methods Clinical specimens from patients with SARS were searched for unknown viruses with the use of cell cultures and molecular techniques. Results A novel coronavirus was identified in patients with SARS. The virus was isolated in cell culture, and a sequence 300 nucleotides in length was obtained by a polymerase-chain-reaction (PCR)–based random-amplification procedure. Genetic characterization indicated that the virus is only distantly related to known coronaviruses (identical in 50 to 60 percent of the nucleotide sequence). On the basis of the obtained sequence, conventional and real-time PCR assays for specific and sensitive detection of the novel virus were established. Virus was detected in a variety of clinical specimens from patients with SARS but not in controls. High concentrations of viral RNA of up to 100 million molecules per milliliter were found in sputum. Viral RNA was also detected at extremely low concentrations in plasma during the acute phase and in feces during the late convalescent phase. Infected patients showed seroconversion on the Vero cells in which the virus was isolated. Conclusions The novel coronavirus might have a role in causing SARS. This study used cell culture and molecular techniques to identify the infectious agent associated with SARS. A novel coronavirus was found in multiple samples from 18 patients but in no specimens from control subjects. In the patients there were high concentrations of viral RNA in sputum, a finding consistent with a highly infectious agent. Low concentrations of viral RNA were also detected in stool. The severe acute respiratory syndrome (SARS) was recently identified as a new clinical entity.1,2 Patients present with fever, dry cough, dyspnea, headache, and hypoxemia. Typical laboratory findings are lymphopenia and mildly elevated aminotransferase levels. Death may result from progressive respiratory failure due to alveolar damage.3 SARS appears to be caused by an unknown infectious agent that is transmitted from human to human. The World Health Organization (WHO) had recorded 2353 cases by April 4, 2003. About 4 percent of patients with SARS have died.4 The SARS epidemic started in Asia, with the majority of cases occurring in China and . . .
Adult–Genetics ; Amino Acid Sequence–Analysis ; Animals–Analysis ; Base Sequence–Blood ; Cattle–Classification ; Coronavirus–Genetics ; DNA, Viral–Isolation & Purification ; Disease Outbreaks–Epidemiology ; Female–Virology ; Humans–Virology ; Male–Virology ; Molecular Sequence Data–Virology ; Phylogeny–Virology ; Polymerase Chain Reaction–Virology ; RNA, Viral–Virology ; RNA, Viral–Virology ; Sars Virus–Virology ; Sars Virus–Virology ; Sars Virus–Virology ; Sequence Homology, Nucleic Acid–Virology ; Severe Acute Respiratory Syndrome–Virology ; Severe Acute Respiratory Syndrome–Virology ; Sputum–Virology ; Singapore ; Germany ; Asia ; Proteins ; Headaches ; Fever ; Patients ; Laboratories ; DNA, Viral ; RNA, Viral ; World Health Organization;