Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome
Identifieur interne : 001872 ( Pmc/Checkpoint ); précédent : 001871; suivant : 001873Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome
Auteurs : Thijs Kuiken [Pays-Bas] ; Ron Am Fouchier [Pays-Bas] ; Martin Schutten [Pays-Bas] ; Guus F. Rimmelzwaan [Pays-Bas] ; Geert Van Amerongen [Pays-Bas] ; Debby Van Riel [Pays-Bas] ; Jon D. Laman [Pays-Bas] ; Ton De Jong [Pays-Bas] ; Gerard Van Doornum [Pays-Bas] ; Wilina Lim [République populaire de Chine] ; Ai Ee Ling [Singapour] ; Paul Ks Chan [Hong Kong] ; John S. Tam [Hong Kong] ; Maria C. Zambon [Royaume-Uni] ; Robin Gopal [Royaume-Uni] ; Christian Drosten [Allemagne] ; Sylvie Van Der Werf [France] ; Nicolas Escriou [France] ; Jean-Claude Manuguerra [France] ; Klaus Stöhr [Suisse] ; J S Malik Peiris ; Albert Dme Osterhaus [Pays-Bas]Source :
- Lancet (London, England) [ 0140-6736 ] ; 2003.
Abstract
The worldwide outbreak of severe acute respiratory syndrome (SARS) is associated with a newly discovered coronavirus, SARS-associated coronavirus (SARSCoV). We did clinical and experimental studies to assess the role of this virus in the cause of SARS.
We tested clinical and postmortem samples from 436 SARS patients in six countries for infection with SARSCoV, 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.
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.
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.
Published online July 22, 2003 http://image.thelancet.com/extras/03art6318web.pdf
Url:
DOI: 10.1016/S0140-6736(03)13967-0
PubMed: 12892955
PubMed Central: 7112434
Affiliations:
- Allemagne, France, Hong Kong, Pays-Bas, Royaume-Uni, République populaire de Chine, Singapour, Suisse
- Angleterre, Grand Londres, Hambourg, Île-de-France
- Hambourg, Londres, Paris, Sha Tin
- Université chinoise de Hong Kong
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Laman</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Immunology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam, Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Immunology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam</wicri:regionArea><wicri:noRegion>3000 DR Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="De Jong, Ton" sort="De Jong, Ton" uniqKey="De Jong T" first="Ton" last="De Jong">Ton De Jong</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Pathology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam, Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Pathology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam</wicri:regionArea><wicri:noRegion>3000 DR Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Van Doornum, Gerard" sort="Van Doornum, Gerard" uniqKey="Van Doornum G" first="Gerard" last="Van Doornum">Gerard Van Doornum</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam, Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam</wicri:regionArea><wicri:noRegion>3000 DR Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Lim, Wilina" sort="Lim, Wilina" uniqKey="Lim W" first="Wilina" last="Lim">Wilina Lim</name><affiliation wicri:level="1"><nlm:aff id="aff4">Government Virus Unit, Public Health Laboratory Centre, Shek Kip Mei, Kowloon, Hong Kong Special Administrative Region, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Government Virus Unit, Public Health Laboratory Centre, Shek Kip Mei, Kowloon, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Ling, Ai Ee" sort="Ling, Ai Ee" uniqKey="Ling A" first="Ai Ee" last="Ling">Ai Ee Ling</name><affiliation wicri:level="1"><nlm:aff id="aff5">Department of Pathology, Singapore General Hospital, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Pathology, Singapore General Hospital</wicri:regionArea><wicri:noRegion>Singapore General Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Chan, Paul Ks" sort="Chan, Paul Ks" uniqKey="Chan P" first="Paul Ks" last="Chan">Paul Ks Chan</name><affiliation wicri:level="4"><nlm:aff id="aff6">Department of Microbiology, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong</nlm:aff><country xml:lang="fr">Hong Kong</country><wicri:regionArea>Department of Microbiology, Chinese University of Hong Kong, Prince of Wales Hospital</wicri:regionArea><orgName type="university">Université chinoise de Hong Kong</orgName><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation></author><author><name sortKey="Tam, John S" sort="Tam, John S" uniqKey="Tam J" first="John S" last="Tam">John S. Tam</name><affiliation wicri:level="4"><nlm:aff id="aff6">Department of Microbiology, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong</nlm:aff><country xml:lang="fr">Hong Kong</country><wicri:regionArea>Department of Microbiology, Chinese University of Hong Kong, Prince of Wales Hospital</wicri:regionArea><orgName type="university">Université chinoise de Hong Kong</orgName><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation></author><author><name sortKey="Zambon, Maria C" sort="Zambon, Maria C" uniqKey="Zambon M" first="Maria C" last="Zambon">Maria C. Zambon</name><affiliation wicri:level="3"><nlm:aff id="aff7">Enteric Respiratory and Neurological Virus Laboratory, Health Protection Agency, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Enteric Respiratory and Neurological Virus Laboratory, Health Protection Agency, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Gopal, Robin" sort="Gopal, Robin" uniqKey="Gopal R" first="Robin" last="Gopal">Robin Gopal</name><affiliation wicri:level="3"><nlm:aff id="aff7">Enteric Respiratory and Neurological Virus Laboratory, Health Protection Agency, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Enteric Respiratory and Neurological Virus Laboratory, Health Protection Agency, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><affiliation wicri:level="3"><nlm:aff id="aff8">Department of Virology, Bernhard-Nocht Institute for Tropical Medicine, Hamburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Virology, Bernhard-Nocht Institute for Tropical Medicine, Hamburg</wicri:regionArea><placeName><settlement type="city">Hambourg</settlement><region type="land" nuts="2">Hambourg</region></placeName></affiliation></author><author><name sortKey="Van Der Werf, Sylvie" sort="Van Der Werf, Sylvie" uniqKey="Van Der Werf S" first="Sylvie" last="Van Der Werf">Sylvie Van Der Werf</name><affiliation wicri:level="3"><nlm:aff id="aff9">Unité de Génétique Moléculaire des Virus Respiratoires, Institut Pasteur, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Génétique Moléculaire des Virus Respiratoires, Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Escriou, Nicolas" sort="Escriou, Nicolas" uniqKey="Escriou N" first="Nicolas" last="Escriou">Nicolas Escriou</name><affiliation wicri:level="3"><nlm:aff id="aff9">Unité de Génétique Moléculaire des Virus Respiratoires, Institut Pasteur, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Génétique Moléculaire des Virus Respiratoires, Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Manuguerra, Jean Claude" sort="Manuguerra, Jean Claude" uniqKey="Manuguerra J" first="Jean-Claude" last="Manuguerra">Jean-Claude Manuguerra</name><affiliation wicri:level="3"><nlm:aff id="aff9">Unité de Génétique Moléculaire des Virus Respiratoires, Institut Pasteur, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Génétique Moléculaire des Virus Respiratoires, Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Stohr, Klaus" sort="Stohr, Klaus" uniqKey="Stohr K" first="Klaus" last="Stöhr">Klaus Stöhr</name><affiliation wicri:level="1"><nlm:aff id="aff10">SARS Aetiology Study Group, WHO, Geneva, Switzerland</nlm:aff><country 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acute respiratory syndrome</title><author><name sortKey="Kuiken, Thijs" sort="Kuiken, Thijs" uniqKey="Kuiken T" first="Thijs" last="Kuiken">Thijs Kuiken</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam, Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam</wicri:regionArea><wicri:noRegion>3000 DR Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Fouchier, Ron Am" sort="Fouchier, Ron Am" uniqKey="Fouchier R" first="Ron Am" last="Fouchier">Ron Am Fouchier</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam, Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam</wicri:regionArea><wicri:noRegion>3000 DR Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Schutten, Martin" sort="Schutten, Martin" uniqKey="Schutten M" first="Martin" last="Schutten">Martin Schutten</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam, Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam</wicri:regionArea><wicri:noRegion>3000 DR Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F" last="Rimmelzwaan">Guus F. Rimmelzwaan</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam, Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam</wicri:regionArea><wicri:noRegion>3000 DR Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Van Amerongen, Geert" sort="Van Amerongen, Geert" uniqKey="Van Amerongen G" first="Geert" last="Van Amerongen">Geert Van Amerongen</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam, Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam</wicri:regionArea><wicri:noRegion>3000 DR Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Van Riel, Debby" sort="Van Riel, Debby" uniqKey="Van Riel D" first="Debby" last="Van Riel">Debby Van Riel</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Immunology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam, Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Immunology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam</wicri:regionArea><wicri:noRegion>3000 DR Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Laman, Jon D" sort="Laman, Jon D" uniqKey="Laman J" first="Jon D" last="Laman">Jon D. Laman</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Immunology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam, Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Immunology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam</wicri:regionArea><wicri:noRegion>3000 DR Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="De Jong, Ton" sort="De Jong, Ton" uniqKey="De Jong T" first="Ton" last="De Jong">Ton De Jong</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Pathology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam, Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Pathology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam</wicri:regionArea><wicri:noRegion>3000 DR Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Van Doornum, Gerard" sort="Van Doornum, Gerard" uniqKey="Van Doornum G" first="Gerard" last="Van Doornum">Gerard Van Doornum</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam, Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam</wicri:regionArea><wicri:noRegion>3000 DR Rotterdam</wicri:noRegion></affiliation></author><author><name sortKey="Lim, Wilina" sort="Lim, Wilina" uniqKey="Lim W" first="Wilina" last="Lim">Wilina Lim</name><affiliation wicri:level="1"><nlm:aff id="aff4">Government Virus Unit, Public Health Laboratory Centre, Shek Kip Mei, Kowloon, Hong Kong Special Administrative Region, China</nlm:aff><country xml:lang="fr">République populaire de Chine</country><wicri:regionArea>Government Virus Unit, Public Health Laboratory Centre, Shek Kip Mei, Kowloon, Hong Kong Special Administrative Region</wicri:regionArea><wicri:noRegion>Hong Kong Special Administrative Region</wicri:noRegion></affiliation></author><author><name sortKey="Ling, Ai Ee" sort="Ling, Ai Ee" uniqKey="Ling A" first="Ai Ee" last="Ling">Ai Ee Ling</name><affiliation wicri:level="1"><nlm:aff id="aff5">Department of Pathology, Singapore General Hospital, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea>Department of Pathology, Singapore General Hospital</wicri:regionArea><wicri:noRegion>Singapore General Hospital</wicri:noRegion></affiliation></author><author><name sortKey="Chan, Paul Ks" sort="Chan, Paul Ks" uniqKey="Chan P" first="Paul Ks" last="Chan">Paul Ks Chan</name><affiliation wicri:level="4"><nlm:aff id="aff6">Department of Microbiology, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong</nlm:aff><country xml:lang="fr">Hong Kong</country><wicri:regionArea>Department of Microbiology, Chinese University of Hong Kong, Prince of Wales Hospital</wicri:regionArea><orgName type="university">Université chinoise de Hong Kong</orgName><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation></author><author><name sortKey="Tam, John S" sort="Tam, John S" uniqKey="Tam J" first="John S" last="Tam">John S. Tam</name><affiliation wicri:level="4"><nlm:aff id="aff6">Department of Microbiology, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong</nlm:aff><country xml:lang="fr">Hong Kong</country><wicri:regionArea>Department of Microbiology, Chinese University of Hong Kong, Prince of Wales Hospital</wicri:regionArea><orgName type="university">Université chinoise de Hong Kong</orgName><placeName><settlement type="city">Sha Tin</settlement></placeName></affiliation></author><author><name sortKey="Zambon, Maria C" sort="Zambon, Maria C" uniqKey="Zambon M" first="Maria C" last="Zambon">Maria C. Zambon</name><affiliation wicri:level="3"><nlm:aff id="aff7">Enteric Respiratory and Neurological Virus Laboratory, Health Protection Agency, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Enteric Respiratory and Neurological Virus Laboratory, Health Protection Agency, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Gopal, Robin" sort="Gopal, Robin" uniqKey="Gopal R" first="Robin" last="Gopal">Robin Gopal</name><affiliation wicri:level="3"><nlm:aff id="aff7">Enteric Respiratory and Neurological Virus Laboratory, Health Protection Agency, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Enteric Respiratory and Neurological Virus Laboratory, Health Protection Agency, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name><affiliation wicri:level="3"><nlm:aff id="aff8">Department of Virology, Bernhard-Nocht Institute for Tropical Medicine, Hamburg, Germany</nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Virology, Bernhard-Nocht Institute for Tropical Medicine, Hamburg</wicri:regionArea><placeName><settlement type="city">Hambourg</settlement><region type="land" nuts="2">Hambourg</region></placeName></affiliation></author><author><name sortKey="Van Der Werf, Sylvie" sort="Van Der Werf, Sylvie" uniqKey="Van Der Werf S" first="Sylvie" last="Van Der Werf">Sylvie Van Der Werf</name><affiliation wicri:level="3"><nlm:aff id="aff9">Unité de Génétique Moléculaire des Virus Respiratoires, Institut Pasteur, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Génétique Moléculaire des Virus Respiratoires, Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Escriou, Nicolas" sort="Escriou, Nicolas" uniqKey="Escriou N" first="Nicolas" last="Escriou">Nicolas Escriou</name><affiliation wicri:level="3"><nlm:aff id="aff9">Unité de Génétique Moléculaire des Virus Respiratoires, Institut Pasteur, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Génétique Moléculaire des Virus Respiratoires, Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Manuguerra, Jean Claude" sort="Manuguerra, Jean Claude" uniqKey="Manuguerra J" first="Jean-Claude" last="Manuguerra">Jean-Claude Manuguerra</name><affiliation wicri:level="3"><nlm:aff id="aff9">Unité de Génétique Moléculaire des Virus Respiratoires, Institut Pasteur, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Unité de Génétique Moléculaire des Virus Respiratoires, Institut Pasteur, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName></affiliation></author><author><name sortKey="Stohr, Klaus" sort="Stohr, Klaus" uniqKey="Stohr K" first="Klaus" last="Stöhr">Klaus Stöhr</name><affiliation wicri:level="1"><nlm:aff id="aff10">SARS Aetiology Study Group, WHO, Geneva, Switzerland</nlm:aff><country xml:lang="fr">Suisse</country><wicri:regionArea>SARS Aetiology Study Group, WHO, Geneva</wicri:regionArea><wicri:noRegion>Geneva</wicri:noRegion></affiliation></author><author><name sortKey="Peiris, J S Malik" sort="Peiris, J S Malik" uniqKey="Peiris J" first="J S Malik" last="Peiris">J S Malik Peiris</name><affiliation><nlm:aff id="aff11">Department of Microbiology and Medicine, Queen Mary Hospital, University of Hong Kong</nlm:aff><wicri:noCountry code="subfield">University of Hong Kong</wicri:noCountry></affiliation></author><author><name sortKey="Osterhaus, Albert Dme" sort="Osterhaus, Albert Dme" uniqKey="Osterhaus A" first="Albert Dme" last="Osterhaus">Albert Dme Osterhaus</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam, Netherlands</nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam</wicri:regionArea><wicri:noRegion>3000 DR Rotterdam</wicri:noRegion></affiliation></author></analytic><series><title level="j">Lancet (London, England)</title><idno type="ISSN">0140-6736</idno><idno type="eISSN">1474-547X</idno><imprint><date when="2003">2003</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><sec><title>Background</title><p>The worldwide outbreak of severe acute respiratory syndrome (SARS) is associated with a newly discovered coronavirus, SARS-associated coronavirus (SARSCoV). We did clinical and experimental studies to assess the role of this virus in the cause of SARS.</p></sec><sec><title>Methods</title><p>We tested clinical and postmortem samples from 436 SARS patients in six countries for infection with SARSCoV, 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.</p></sec><sec><title>Findings</title><p>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.</p></sec><sec><title>Interpretation</title><p>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.</p><p>Published online July 22, 2003 http://image.thelancet.com/extras/03art6318web.pdf</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Peiris, Js" uniqKey="Peiris J">JS Peiris</name></author><author><name sortKey="Lai, St" uniqKey="Lai S">ST Lai</name></author><author><name sortKey="Poon, Ll" uniqKey="Poon L">LL Poon</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Lee, N" 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Lancet</journal-id><journal-id journal-id-type="iso-abbrev">Lancet</journal-id><journal-title-group><journal-title>Lancet (London, England)</journal-title></journal-title-group><issn pub-type="ppub">0140-6736</issn><issn pub-type="epub">1474-547X</issn><publisher><publisher-name>Elsevier Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">12892955</article-id><article-id pub-id-type="pmc">7112434</article-id><article-id pub-id-type="publisher-id">S0140-6736(03)13967-0</article-id><article-id pub-id-type="doi">10.1016/S0140-6736(03)13967-0</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Newly discovered coronavirus as the primary cause of severe acute respiratory syndrome</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Kuiken</surname><given-names>Thijs</given-names></name><degrees>PhD</degrees><email>t.kuiken@erasmusmc.nl</email><xref rid="aff1" ref-type="aff">a</xref><xref rid="cor1" ref-type="corresp">*</xref></contrib><contrib contrib-type="author"><name><surname>Fouchier</surname><given-names>Ron AM</given-names></name><degrees>PhD</degrees><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Schutten</surname><given-names>Martin</given-names></name><degrees>PhD</degrees><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Rimmelzwaan</surname><given-names>Guus F</given-names></name><degrees>PhD</degrees><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>van Amerongen</surname><given-names>Geert</given-names></name><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>van Riel</surname><given-names>Debby</given-names></name><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author"><name><surname>Laman</surname><given-names>Jon D</given-names></name><degrees>PhD</degrees><xref rid="aff2" ref-type="aff">b</xref></contrib><contrib contrib-type="author"><name><surname>de Jong</surname><given-names>Ton</given-names></name><xref rid="aff3" ref-type="aff">c</xref></contrib><contrib contrib-type="author"><name><surname>van Doornum</surname><given-names>Gerard</given-names></name><degrees>PhD</degrees><xref rid="aff1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><name><surname>Lim</surname><given-names>Wilina</given-names></name><degrees>MD</degrees><xref rid="aff4" ref-type="aff">d</xref></contrib><contrib contrib-type="author"><name><surname>Ling</surname><given-names>Ai Ee</given-names></name><degrees>FRCPA</degrees><xref rid="aff5" ref-type="aff">e</xref></contrib><contrib contrib-type="author"><name><surname>Chan</surname><given-names>Paul KS</given-names></name><degrees>MD</degrees><xref rid="aff6" ref-type="aff">f</xref></contrib><contrib contrib-type="author"><name><surname>Tam</surname><given-names>John S</given-names></name><degrees>PhD</degrees><xref rid="aff6" ref-type="aff">f</xref></contrib><contrib contrib-type="author"><name><surname>Zambon</surname><given-names>Maria C</given-names></name><degrees>PhD</degrees><xref rid="aff7" ref-type="aff">g</xref></contrib><contrib contrib-type="author"><name><surname>Gopal</surname><given-names>Robin</given-names></name><degrees>PhD</degrees><xref rid="aff7" ref-type="aff">g</xref></contrib><contrib contrib-type="author"><name><surname>Drosten</surname><given-names>Christian</given-names></name><degrees>MD</degrees><xref rid="aff8" ref-type="aff">h</xref></contrib><contrib contrib-type="author"><name><surname>van der Werf</surname><given-names>Sylvie</given-names></name><degrees>PhD</degrees><xref rid="aff9" ref-type="aff">i</xref></contrib><contrib contrib-type="author"><name><surname>Escriou</surname><given-names>Nicolas</given-names></name><degrees>PhD</degrees><xref rid="aff9" ref-type="aff">i</xref></contrib><contrib contrib-type="author"><name><surname>Manuguerra</surname><given-names>Jean-Claude</given-names></name><degrees>PhD</degrees><xref rid="aff9" ref-type="aff">i</xref></contrib><contrib contrib-type="author"><name><surname>Stöhr</surname><given-names>Klaus</given-names></name><degrees>PhD</degrees><xref rid="aff10" ref-type="aff">j</xref></contrib><contrib contrib-type="author"><name><surname>Peiris</surname><given-names>J S Malik</given-names></name><degrees>DPhil</degrees><xref rid="aff11" ref-type="aff">k</xref></contrib><contrib contrib-type="author"><name><surname>Osterhaus</surname><given-names>Albert DME</given-names></name><degrees>PhD</degrees><xref rid="aff1" ref-type="aff">a</xref></contrib></contrib-group><aff id="aff1"><label>a</label>Department of Virology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam, Netherlands</aff><aff id="aff2"><label>b</label>Department of Immunology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam, Netherlands</aff><aff id="aff3"><label>c</label>Department of Pathology, Erasmus Medical Centre, PO Box 1738, 3000 DR Rotterdam, Netherlands</aff><aff id="aff4"><label>d</label>Government Virus Unit, Public Health Laboratory Centre, Shek Kip Mei, Kowloon, Hong Kong Special Administrative Region, China</aff><aff id="aff5"><label>e</label>Department of Pathology, Singapore General Hospital, Singapore</aff><aff id="aff6"><label>f</label>Department of Microbiology, Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong</aff><aff id="aff7"><label>g</label>Enteric Respiratory and Neurological Virus Laboratory, Health Protection Agency, London, UK</aff><aff id="aff8"><label>h</label>Department of Virology, Bernhard-Nocht Institute for Tropical Medicine, Hamburg, Germany</aff><aff id="aff9"><label>i</label>Unité de Génétique Moléculaire des Virus Respiratoires, Institut Pasteur, Paris, France</aff><aff id="aff10"><label>j</label>SARS Aetiology Study Group, WHO, Geneva, Switzerland</aff><aff id="aff11"><label>k</label>Department of Microbiology and Medicine, Queen Mary Hospital, University of Hong Kong</aff><author-notes><corresp id="cor1"><label>*</label>Correspondence to: Dr Thijs Kuiken <email>t.kuiken@erasmusmc.nl</email></corresp></author-notes><pub-date pub-type="pmc-release"><day>24</day><month>7</month><year>2003</year></pub-date><pmc-comment> PMC Release delay is 0 months and 0 days and was based on .</pmc-comment>
<pub-date pub-type="ppub"><day>26</day><month>7</month><year>2003</year></pub-date><pub-date pub-type="epub"><day>24</day><month>7</month><year>2003</year></pub-date><volume>362</volume><issue>9380</issue><fpage>263</fpage><lpage>270</lpage><permissions><copyright-statement>Copyright © 2003 Elsevier Ltd. All rights reserved.</copyright-statement><copyright-year>2003</copyright-year><copyright-holder>Elsevier Ltd</copyright-holder><license><license-p>Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.</license-p></license></permissions><abstract><title>Summary</title><sec><title>Background</title><p>The worldwide outbreak of severe acute respiratory syndrome (SARS) is associated with a newly discovered coronavirus, SARS-associated coronavirus (SARSCoV). We did clinical and experimental studies to assess the role of this virus in the cause of SARS.</p></sec><sec><title>Methods</title><p>We tested clinical and postmortem samples from 436 SARS patients in six countries for infection with SARSCoV, 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.</p></sec><sec><title>Findings</title><p>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.</p></sec><sec><title>Interpretation</title><p>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.</p><p>Published online July 22, 2003 http://image.thelancet.com/extras/03art6318web.pdf</p></sec></abstract></article-meta></front></pmc><affiliations><list><country><li>Allemagne</li><li>France</li><li>Hong Kong</li><li>Pays-Bas</li><li>Royaume-Uni</li><li>République populaire de Chine</li><li>Singapour</li><li>Suisse</li></country><region><li>Angleterre</li><li>Grand Londres</li><li>Hambourg</li><li>Île-de-France</li></region><settlement><li>Hambourg</li><li>Londres</li><li>Paris</li><li>Sha Tin</li></settlement><orgName><li>Université chinoise de Hong Kong</li></orgName></list><tree><noCountry><name sortKey="Peiris, J S Malik" sort="Peiris, J S Malik" uniqKey="Peiris J" first="J S Malik" last="Peiris">J S Malik Peiris</name></noCountry><country name="Pays-Bas"><noRegion><name sortKey="Kuiken, Thijs" sort="Kuiken, Thijs" uniqKey="Kuiken T" first="Thijs" last="Kuiken">Thijs Kuiken</name></noRegion><name sortKey="De Jong, Ton" sort="De Jong, Ton" uniqKey="De Jong T" first="Ton" last="De Jong">Ton De Jong</name><name sortKey="Fouchier, Ron Am" sort="Fouchier, Ron Am" uniqKey="Fouchier R" first="Ron Am" last="Fouchier">Ron Am Fouchier</name><name sortKey="Laman, Jon D" sort="Laman, Jon D" uniqKey="Laman J" first="Jon D" last="Laman">Jon D. Laman</name><name sortKey="Osterhaus, Albert Dme" sort="Osterhaus, Albert Dme" uniqKey="Osterhaus A" first="Albert Dme" last="Osterhaus">Albert Dme Osterhaus</name><name sortKey="Rimmelzwaan, Guus F" sort="Rimmelzwaan, Guus F" uniqKey="Rimmelzwaan G" first="Guus F" last="Rimmelzwaan">Guus F. Rimmelzwaan</name><name sortKey="Schutten, Martin" sort="Schutten, Martin" uniqKey="Schutten M" first="Martin" last="Schutten">Martin Schutten</name><name sortKey="Van Amerongen, Geert" sort="Van Amerongen, Geert" uniqKey="Van Amerongen G" first="Geert" last="Van Amerongen">Geert Van Amerongen</name><name sortKey="Van Doornum, Gerard" sort="Van Doornum, Gerard" uniqKey="Van Doornum G" first="Gerard" last="Van Doornum">Gerard Van Doornum</name><name sortKey="Van Riel, Debby" sort="Van Riel, Debby" uniqKey="Van Riel D" first="Debby" last="Van Riel">Debby Van Riel</name></country><country name="République populaire de Chine"><noRegion><name sortKey="Lim, Wilina" sort="Lim, Wilina" uniqKey="Lim W" first="Wilina" last="Lim">Wilina Lim</name></noRegion></country><country name="Singapour"><noRegion><name sortKey="Ling, Ai Ee" sort="Ling, Ai Ee" uniqKey="Ling A" first="Ai Ee" last="Ling">Ai Ee Ling</name></noRegion></country><country name="Hong Kong"><noRegion><name sortKey="Chan, Paul Ks" sort="Chan, Paul Ks" uniqKey="Chan P" first="Paul Ks" last="Chan">Paul Ks Chan</name></noRegion><name sortKey="Tam, John S" sort="Tam, John S" uniqKey="Tam J" first="John S" last="Tam">John S. Tam</name></country><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="Zambon, Maria C" sort="Zambon, Maria C" uniqKey="Zambon M" first="Maria C" last="Zambon">Maria C. Zambon</name></region><name sortKey="Gopal, Robin" sort="Gopal, Robin" uniqKey="Gopal R" first="Robin" last="Gopal">Robin Gopal</name></country><country name="Allemagne"><region name="Hambourg"><name sortKey="Drosten, Christian" sort="Drosten, Christian" uniqKey="Drosten C" first="Christian" last="Drosten">Christian Drosten</name></region></country><country name="France"><region name="Île-de-France"><name sortKey="Van Der Werf, Sylvie" sort="Van Der Werf, Sylvie" uniqKey="Van Der Werf S" first="Sylvie" last="Van Der Werf">Sylvie Van Der Werf</name></region><name sortKey="Escriou, Nicolas" sort="Escriou, Nicolas" uniqKey="Escriou N" first="Nicolas" last="Escriou">Nicolas Escriou</name><name sortKey="Manuguerra, Jean Claude" sort="Manuguerra, Jean Claude" uniqKey="Manuguerra J" first="Jean-Claude" last="Manuguerra">Jean-Claude Manuguerra</name></country><country name="Suisse"><noRegion><name sortKey="Stohr, Klaus" sort="Stohr, Klaus" uniqKey="Stohr K" first="Klaus" last="Stöhr">Klaus Stöhr</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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