Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome.
BACKGROUND
The worldwide outbreak of severe acute respiratory syndrome (SARS) is associated with a newly discovered coronavirus, SARS-associated coronavirus (SARS-CoV). We did clinical and experimental studies to assess the role of this virus in the cause of SARS.


METHODS
We tested clinical and postmortem samples from 436 SARS patients in six countries for infection with SARS-CoV, human metapneumovirus, and other respiratory pathogens. We infected four cynomolgus macaques (Macaca fascicularis) with SARS-CoV in an attempt to replicate SARS and did necropsies on day 6 after infection.


RESULTS
SARS-CoV infection was diagnosed in 329 (75%) of 436 patients fitting the case definition of SARS; human metapneumovirus was diagnosed in 41 (12%) of 335, and other respiratory pathogens were diagnosed only sporadically. SARS-CoV was, therefore, the most likely causal agent of SARS. The four SARS-CoV-infected macaques excreted SARS-CoV from nose, mouth, and pharynx from 2 days after infection. Three of four macaques developed diffuse alveolar damage, similar to that in SARS patients, and characterised by epithelial necrosis, serosanguineous exudate, formation of hyaline membranes, type 2 pneumocyte hyperplasia, and the presence of syncytia. SARS-CoV was detected in pneumonic areas by virus isolation and RT-PCR, and was localised to alveolar epithelial cells and syncytia by immunohistochemistry and transmission electron microscopy.


CONCLUSIONS
Replication in SARS-CoV-infected macaques of pneumonia similar to that in human beings with SARS, combined with the high prevalence of SARS-CoV infection in SARS patients, fulfill the criteria required to prove that SARS-CoV is the primary cause of SARS.
Kuiken
Thijs
T
Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR, Rotterdam, Netherlands. t.kuiken@erasmusmc.nl <t.kuiken@erasmusmc.nl>
Fouchier
Ron A M
RA
Schutten
Martin
M
Rimmelzwaan
Guus F
GF
van Amerongen
Geert
G
van Riel
Debby
D
Laman
Jon D
JD
de Jong
Ton
T
van Doornum
Gerard
G
Lim
Wilina
W
Ling
Ai Ee
AE
Chan
Paul K S
PK
Tam
John S
JS
Zambon
Maria C
MC
Gopal
Robin
R
Drosten
Christian
C
van der Werf
Sylvie
S
Escriou
Nicolas
N
Manuguerra
Jean-Claude
JC
Stöhr
Klaus
K
Peiris
J S Malik
JS
Osterhaus
Albert D M E
AD
D000818:Animals; D002681:China / Q000453:epidemiology; D021821:Communicable Diseases, Emerging / Q000453:epidemiology / Q000821:virology; D004195:Disease Models, Animal; D004196:Disease Outbreaks; D014943:Global Health; D006801:Humans; D008252:Macaca fascicularis; D011650:Pulmonary Alveoli / Q000473:pathology / Q000821:virology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000302:isolation & purification* / Q000472:pathogenicity; D045169:Severe Acute Respiratory Syndrome / Q000453:epidemiology / Q000473:pathology / Q000821:virology*