Identification of a novel coronavirus in patients with severe acute respiratory syndrome.
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.
Drosten
Christian
C
Bernhard Nocht Institute for Tropical Medicine, National Reference Center for Tropical Infectious Diseases, Hamburg, Germany. drosten@bni-hamburg.de
Günther
Stephan
S
Preiser
Wolfgang
W
van der Werf
Sylvie
S
Brodt
Hans-Reinhard
HR
Becker
Stephan
S
Rabenau
Holger
H
Panning
Marcus
M
Kolesnikova
Larissa
L
Fouchier
Ron A M
RA
Berger
Annemarie
A
Burguière
Ana-Maria
AM
Cinatl
Jindrich
J
Eickmann
Markus
M
Escriou
Nicolas
N
Grywna
Klaus
K
Kramme
Stefanie
S
Manuguerra
Jean-Claude
JC
Müller
Stefanie
S
Rickerts
Volker
V
Stürmer
Martin
M
Vieth
Simon
S
Klenk
Hans-Dieter
HD
Osterhaus
Albert D M E
AD
Schmitz
Herbert
H
Doerr
Hans Wilhelm
HW
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002417:Cattle; D017934:Coronavirus / Q000235:genetics; D004279:DNA, Viral / Q000032:analysis; D004196:Disease Outbreaks; D005260:Female; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis / Q000097:blood; D045473:Severe acute respiratory syndrome-related coronavirus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification*; D012689:Sequence Homology, Nucleic Acid; D045169:Severe Acute Respiratory Syndrome / Q000453:epidemiology / Q000821:virology*; D013183:Sputum / Q000821:virology
D004279:DNA, Viral; D012367:RNA, Viral