Nasopharyngeal Shedding of Severe Acute Respiratory Syndrome—Associated Coronavirus Is Associated with Genetic Polymorphisms
Identifieur interne : 004060 ( Main/Curation ); précédent : 004059; suivant : 004061Nasopharyngeal Shedding of Severe Acute Respiratory Syndrome—Associated Coronavirus Is Associated with Genetic Polymorphisms
Auteurs : Wei-Ju Chen [Taïwan] ; Jyh-Yuan Yang [Taïwan] ; Jih-Hui Lin [Taïwan] ; Cathy S. J. Fann [Taïwan] ; Valeriy Osyetrov [Taïwan] ; Chwan-Chuen King [Taïwan] ; Yi-Ming Arthur Chen [Taïwan] ; Hsiao-Ling Chang [Taïwan] ; Hung-Wei Kuo [Taïwan] ; Fong Liao [Taïwan] ; Mei-Shang Ho [Taïwan]Source :
- Clinical Infectious Diseases [ 1058-4838 ] ; 2006.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Analyse multivariée, Charge virale, Excrétion virale (génétique), Facteur de transcription RelB (génétique), Femelle, Fibrinogène (génétique), Humains, Interleukine-1 (génétique), Interleukine-18 (génétique), Modèles logistiques, Mâle, Partie nasale du pharynx (virologie), Polymorphisme génétique, Sujet âgé, Virus du SRAS (physiologie).
- MESH :
- génétique : Excrétion virale, Facteur de transcription RelB, Fibrinogène, Interleukine-1, Interleukine-18.
- physiologie : Virus du SRAS.
- virologie : Partie nasale du pharynx.
- Adulte, Adulte d'âge moyen, Analyse multivariée, Charge virale, Femelle, Humains, Modèles logistiques, Mâle, Polymorphisme génétique, Sujet âgé.
- Pascal (Inist)
English descriptors
- KwdEn :
- Adult, Aged, Coronavirus, Female, Fibrinogen (genetics), Humans, Interleukin-1 (genetics), Interleukin-18 (genetics), Logistic Models, Male, Middle Aged, Multivariate Analysis, Nasopharynx, Nasopharynx (virology), Polymorphism, Polymorphism, Genetic, SARS Virus (physiology), Severe acute respiratory syndrome, Transcription Factor RelB (genetics), Viral Load, Virus Shedding (genetics).
- MESH :
- chemical , genetics : Fibrinogen, Interleukin-1, Interleukin-18, Transcription Factor RelB.
- genetics : Virus Shedding.
- physiology : SARS Virus.
- virology : Nasopharynx.
- Adult, Aged, Female, Humans, Logistic Models, Male, Middle Aged, Multivariate Analysis, Polymorphism, Genetic, Viral Load.
Abstract
Background. A high initial or peak severe acute respiratory syndrome (SARS)—associated coronavirus (SARS-CoV) load in nasopharyngeal specimens was shown to be associated with a high mortality rate. Because all infected individuals were devoid of preeexisting protective immunity against SARS-CoV, the biological basis for the variable virus burdens in different patients remains elusive. Methods. The nationwide SARS database in Taiwan was analyzed, and genotyping of 281 single-nucleotide polymorphisms (SNPs) of 65 genes was performed for 94 patients with SARS, to identify SNPs for which distribution between patients with or without detectable nasopharyngeal shedding of SARS-CoV was biased. Results. Titers of SARS-CoV shed in nasopharyngeal specimens varied widely, ranging from nondetectable to 108 SARS-CoV RNA copies/mL, and they were correlated positively with a high mortality rate (P < .0001, by trend test) and with early death (i.e., death occurring within 2 weeks of the onset of illness) (P = .0015, by trend test). Virus shedding was found to be higher among male patients (P = .0014, by multivariate logistic regression) and among older patients (P = .015, by multivariate logistic regression). Detectable nasopharyngeal shedding of SARS-CoV was associated with polymorphic alleles of interleukins 18 (P = .014) and 1A (P = .031) and a member of NFκB complex (reticuloendotheliosis viral oncogene homolog B [RelB]) (P = .034), all of which are proinflammatory in nature, as well as the procoagulation molecule fibrinogen-like protein 2 (P = .008). Conclusion. The SARS-CoV load is a determinant of clinical outcomes of SARS, and it is associated with polymorphisms of genes involved in innate immunity, which might be regulated in an age- and sex-dependent manner. The findings of the present study provided leads to genes involved in the host response to SARS-CoV infection; if substantiated with functional studies, these findings may be applicable to other newly emerged respiratory viruses (e.g., the influenza pandemic strain).
Url:
- https://api.istex.fr/ark:/67375/HXZ-HB5XDM1W-T/fulltext.pdf
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7107974
DOI: 10.1086/503843
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<term>Humans</term>
<term>Interleukin-1 (genetics)</term>
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<term>Middle Aged</term>
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<term>Severe acute respiratory syndrome</term>
<term>Transcription Factor RelB (genetics)</term>
<term>Viral Load</term>
<term>Virus Shedding (genetics)</term>
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<term>Adulte d'âge moyen</term>
<term>Analyse multivariée</term>
<term>Charge virale</term>
<term>Excrétion virale (génétique)</term>
<term>Facteur de transcription RelB (génétique)</term>
<term>Femelle</term>
<term>Fibrinogène (génétique)</term>
<term>Humains</term>
<term>Interleukine-1 (génétique)</term>
<term>Interleukine-18 (génétique)</term>
<term>Modèles logistiques</term>
<term>Mâle</term>
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<term>Polymorphisme génétique</term>
<term>Sujet âgé</term>
<term>Virus du SRAS (physiologie)</term>
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<term>Interleukin-18</term>
<term>Transcription Factor RelB</term>
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<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Virus Shedding</term>
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<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Excrétion virale</term>
<term>Facteur de transcription RelB</term>
<term>Fibrinogène</term>
<term>Interleukine-1</term>
<term>Interleukine-18</term>
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<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus du SRAS</term>
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<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>SARS Virus</term>
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<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Partie nasale du pharynx</term>
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<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Nasopharynx</term>
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<term>Aged</term>
<term>Female</term>
<term>Humans</term>
<term>Logistic Models</term>
<term>Male</term>
<term>Middle Aged</term>
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<term>Polymorphism, Genetic</term>
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<term>Charge virale</term>
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<front><div type="abstract">Background. A high initial or peak severe acute respiratory syndrome (SARS)—associated coronavirus (SARS-CoV) load in nasopharyngeal specimens was shown to be associated with a high mortality rate. Because all infected individuals were devoid of preeexisting protective immunity against SARS-CoV, the biological basis for the variable virus burdens in different patients remains elusive. Methods. The nationwide SARS database in Taiwan was analyzed, and genotyping of 281 single-nucleotide polymorphisms (SNPs) of 65 genes was performed for 94 patients with SARS, to identify SNPs for which distribution between patients with or without detectable nasopharyngeal shedding of SARS-CoV was biased. Results. Titers of SARS-CoV shed in nasopharyngeal specimens varied widely, ranging from nondetectable to 108 SARS-CoV RNA copies/mL, and they were correlated positively with a high mortality rate (P < .0001, by trend test) and with early death (i.e., death occurring within 2 weeks of the onset of illness) (P = .0015, by trend test). Virus shedding was found to be higher among male patients (P = .0014, by multivariate logistic regression) and among older patients (P = .015, by multivariate logistic regression). Detectable nasopharyngeal shedding of SARS-CoV was associated with polymorphic alleles of interleukins 18 (P = .014) and 1A (P = .031) and a member of NFκB complex (reticuloendotheliosis viral oncogene homolog B [RelB]) (P = .034), all of which are proinflammatory in nature, as well as the procoagulation molecule fibrinogen-like protein 2 (P = .008). Conclusion. The SARS-CoV load is a determinant of clinical outcomes of SARS, and it is associated with polymorphisms of genes involved in innate immunity, which might be regulated in an age- and sex-dependent manner. The findings of the present study provided leads to genes involved in the host response to SARS-CoV infection; if substantiated with functional studies, these findings may be applicable to other newly emerged respiratory viruses (e.g., the influenza pandemic strain).</div>
</front>
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<author><name sortKey="Lin, Jih Hui" sort="Lin, Jih Hui" uniqKey="Lin J" first="Jih-Hui" last="Lin">Jih-Hui Lin</name>
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</affiliation>
</author>
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</author>
<author><name sortKey="Chang, Hsiao Ling" sort="Chang, Hsiao Ling" uniqKey="Chang H" first="Hsiao-Ling" last="Chang">Hsiao-Ling Chang</name>
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</affiliation>
</author>
<author><name sortKey="Kuo, Hung Wei" sort="Kuo, Hung Wei" uniqKey="Kuo H" first="Hung-Wei" last="Kuo">Hung-Wei Kuo</name>
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</affiliation>
</author>
<author><name sortKey="Fong Liao" sort="Fong Liao" uniqKey="Fong Liao" last="Fong Liao">FONG LIAO</name>
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</affiliation>
</author>
<author><name sortKey="Ho, Mei Shang" sort="Ho, Mei Shang" uniqKey="Ho M" first="Mei-Shang" last="Ho">Mei-Shang Ho</name>
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</affiliation>
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<wicri:noRegion>Graduate Institute of Epidemiology, National Taiwan University</wicri:noRegion>
</affiliation>
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<date when="2006">2006</date>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Nasopharyngeal shedding of severe acute respiratory syndrome-associated coronavirus is associated with genetic polymorphisms</title>
<author><name sortKey="Chen, Wei Ju" sort="Chen, Wei Ju" uniqKey="Chen W" first="Wei-Ju" last="Chen">Wei-Ju Chen</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institute of Biomedical Science, Academia Sinica, National Taiwan University</s1>
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</inist:fA14>
<country>Taïwan</country>
<wicri:noRegion>Institute of Biomedical Science, Academia Sinica, National Taiwan University</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Yang, Jyh Yuan" sort="Yang, Jyh Yuan" uniqKey="Yang J" first="Jyh-Yuan" last="Yang">Jyh-Yuan Yang</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Center for Disease Control, National Taiwan University</s1>
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<country>Taïwan</country>
<wicri:noRegion>Center for Disease Control, National Taiwan University</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lin, Jih Hui" sort="Lin, Jih Hui" uniqKey="Lin J" first="Jih-Hui" last="Lin">Jih-Hui Lin</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Center for Disease Control, National Taiwan University</s1>
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<country>Taïwan</country>
<wicri:noRegion>Center for Disease Control, National Taiwan University</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Fann, Cathy S J" sort="Fann, Cathy S J" uniqKey="Fann C" first="Cathy S. J." last="Fann">Cathy S. J. Fann</name>
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</inist:fA14>
<country>Taïwan</country>
<wicri:noRegion>Institute of Biomedical Science, Academia Sinica, National Taiwan University</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Osyetrov, Valeriy" sort="Osyetrov, Valeriy" uniqKey="Osyetrov V" first="Valeriy" last="Osyetrov">Valeriy Osyetrov</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institute of Biomedical Science, Academia Sinica, National Taiwan University</s1>
<s3>TWN</s3>
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<sZ>5 aut.</sZ>
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<country>Taïwan</country>
<wicri:noRegion>Institute of Biomedical Science, Academia Sinica, National Taiwan University</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="King, Chwan Chuen" sort="King, Chwan Chuen" uniqKey="King C" first="Chwan-Chuen" last="King">Chwan-Chuen King</name>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Graduate Institute of Epidemiology, National Taiwan University</s1>
<s3>TWN</s3>
<sZ>6 aut.</sZ>
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</inist:fA14>
<country>Taïwan</country>
<wicri:noRegion>Graduate Institute of Epidemiology, National Taiwan University</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chen, Yi Ming Arthur" sort="Chen, Yi Ming Arthur" uniqKey="Chen Y" first="Yi-Ming Arthur" last="Chen">Yi-Ming Arthur Chen</name>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Institute of Public Health, National Yang-Ming University</s1>
<s2>Taipei</s2>
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<country>Taïwan</country>
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</affiliation>
</author>
<author><name sortKey="Chang, Hsiao Ling" sort="Chang, Hsiao Ling" uniqKey="Chang H" first="Hsiao-Ling" last="Chang">Hsiao-Ling Chang</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Center for Disease Control, National Taiwan University</s1>
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</inist:fA14>
<country>Taïwan</country>
<wicri:noRegion>Center for Disease Control, National Taiwan University</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kuo, Hung Wei" sort="Kuo, Hung Wei" uniqKey="Kuo H" first="Hung-Wei" last="Kuo">Hung-Wei Kuo</name>
<affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Center for Disease Control, National Taiwan University</s1>
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<sZ>2 aut.</sZ>
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<sZ>9 aut.</sZ>
</inist:fA14>
<country>Taïwan</country>
<wicri:noRegion>Center for Disease Control, National Taiwan University</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Fong Liao" sort="Fong Liao" uniqKey="Fong Liao" last="Fong Liao">FONG LIAO</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institute of Biomedical Science, Academia Sinica, National Taiwan University</s1>
<s3>TWN</s3>
<sZ>1 aut.</sZ>
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<sZ>5 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>Taïwan</country>
<wicri:noRegion>Institute of Biomedical Science, Academia Sinica, National Taiwan University</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ho, Mei Shang" sort="Ho, Mei Shang" uniqKey="Ho M" first="Mei-Shang" last="Ho">Mei-Shang Ho</name>
<affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Institute of Biomedical Science, Academia Sinica, National Taiwan University</s1>
<s3>TWN</s3>
<sZ>1 aut.</sZ>
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<sZ>5 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>Taïwan</country>
<wicri:noRegion>Institute of Biomedical Science, Academia Sinica, National Taiwan University</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Graduate Institute of Epidemiology, National Taiwan University</s1>
<s3>TWN</s3>
<sZ>6 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>Taïwan</country>
<wicri:noRegion>Graduate Institute of Epidemiology, National Taiwan University</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Institute of Public Health, National Yang-Ming University</s1>
<s2>Taipei</s2>
<s3>TWN</s3>
<sZ>7 aut.</sZ>
<sZ>11 aut.</sZ>
</inist:fA14>
<country>Taïwan</country>
<wicri:noRegion>Taipei</wicri:noRegion>
</affiliation>
</author>
</analytic>
<series><title level="j" type="main">Clinical infectious diseases</title>
<title level="j" type="abbreviated">Clin. infect. dis.</title>
<idno type="ISSN">1058-4838</idno>
<imprint><date when="2006">2006</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
<seriesStmt><title level="j" type="main">Clinical infectious diseases</title>
<title level="j" type="abbreviated">Clin. infect. dis.</title>
<idno type="ISSN">1058-4838</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Coronavirus</term>
<term>Nasopharynx</term>
<term>Polymorphism</term>
<term>Severe acute respiratory syndrome</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term>
<term>Nasopharynx</term>
<term>Polymorphisme</term>
<term>Coronavirus</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Background. A high initial or peak severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) load in nasopharyngeal specimens was shown to be associated with a high mortality rate. Because all infected individuals were devoid of preeexisting protective immunity against SARS-CoV, the biological basis for the variable virus burdens in different patients remains elusive. Methods. The nationwide SARS database in Taiwan was analyzed, and genotyping of 281 single-nucleotide polymorphisms (SNPs) of 65 genes was performed for 94 patients with SARS, to identify SNPs for which distribution between patients with or without detectable nasopharyngeal shedding of SARS-CoV was biased. Results. Titers of SARS-CoV shed in nasopharyngeal specimens varied widely, ranging from nondetectable to 10<sup>8</sup>
SARS-CoV RNA copies/mL, and they were correlated positively with a high mortality rate (P<.0001, by trend test) and with early death (i.e., death occurring within 2 weeks of the onset of illness) (P =.0015, by trend test). Virus shedding was found to be higher among male patients (P =.0014, by multivariate logistic regression) and among older patients (P =.015, by multivariate logistic regression). Detectable nasopharyngeal shedding of SARS-CoV was associated with polymorphic alleles of interleukins 18 (P =.014) and 1A (P =.031) and a member of NFκB complex (reticuloendotheliosis viral oncogene homolog B [RelB]) (P =.034), all of which are proinflammatory in nature, as well as the procoagulation molecule fibrinogen-like protein 2 (P =.008). Conclusion. The SARS-CoV load is a determinant of clinical outcomes of SARS, and it is associated with polymorphisms of genes involved in innate immunity, which might be regulated in an age- and sex-dependent manner. The findings of the present study provided leads to genes involved in the host response to SARS-CoV infection; if substantiated with functional studies, these findings may be applicable to other newly emerged respiratory viruses (e.g., the influenza pandemic strain).</div>
</front>
</TEI>
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<author><name sortKey="Yang, Jyh Yuan" sort="Yang, Jyh Yuan" uniqKey="Yang J" first="Jyh-Yuan" last="Yang">Jyh-Yuan Yang</name>
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<author><name sortKey="Chang, Hsiao Ling" sort="Chang, Hsiao Ling" uniqKey="Chang H" first="Hsiao-Ling" last="Chang">Hsiao-Ling Chang</name>
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<author><name sortKey="Kuo, Hung Wei" sort="Kuo, Hung Wei" uniqKey="Kuo H" first="Hung-Wei" last="Kuo">Hung-Wei Kuo</name>
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<author><name sortKey="Liao, Fong" sort="Liao, Fong" uniqKey="Liao F" first="Fong" last="Liao">Fong Liao</name>
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<author><name sortKey="Ho, Mei Shang" sort="Ho, Mei Shang" uniqKey="Ho M" first="Mei-Shang" last="Ho">Mei-Shang Ho</name>
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</affiliation>
</author>
<author><name sortKey="Yang, Jyh Yuan" sort="Yang, Jyh Yuan" uniqKey="Yang J" first="Jyh-Yuan" last="Yang">Jyh-Yuan Yang</name>
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<wicri:regionArea>Center for Disease Control, Taipei</wicri:regionArea>
<wicri:noRegion>Taipei</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Lin, Jih Hui" sort="Lin, Jih Hui" uniqKey="Lin J" first="Jih-Hui" last="Lin">Jih-Hui Lin</name>
<affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Center for Disease Control, Taipei</wicri:regionArea>
<wicri:noRegion>Taipei</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Fann, Cathy S J" sort="Fann, Cathy S J" uniqKey="Fann C" first="Cathy S. J." last="Fann">Cathy S. J. Fann</name>
<affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Institute of Biomedical Science, Academia Sinica, Taipei</wicri:regionArea>
<wicri:noRegion>Taipei</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Osyetrov, Valeriy" sort="Osyetrov, Valeriy" uniqKey="Osyetrov V" first="Valeriy" last="Osyetrov">Valeriy Osyetrov</name>
<affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Institute of Biomedical Science, Academia Sinica, Taipei</wicri:regionArea>
<wicri:noRegion>Taipei</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="King, Chwan Chuen" sort="King, Chwan Chuen" uniqKey="King C" first="Chwan-Chuen" last="King">Chwan-Chuen King</name>
<affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Graduate Institute of Epidemiology, National Taiwan University, Taipei</wicri:regionArea>
<wicri:noRegion>Taipei</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chen, Yi Ming Arthur" sort="Chen, Yi Ming Arthur" uniqKey="Chen Y" first="Yi-Ming Arthur" last="Chen">Yi-Ming Arthur Chen</name>
<affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Institute of Public Health, National Yang-Ming University, Taipei</wicri:regionArea>
<wicri:noRegion>Taipei</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chang, Hsiao Ling" sort="Chang, Hsiao Ling" uniqKey="Chang H" first="Hsiao-Ling" last="Chang">Hsiao-Ling Chang</name>
<affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Center for Disease Control, Taipei</wicri:regionArea>
<wicri:noRegion>Taipei</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Kuo, Hung Wei" sort="Kuo, Hung Wei" uniqKey="Kuo H" first="Hung-Wei" last="Kuo">Hung-Wei Kuo</name>
<affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Center for Disease Control, Taipei</wicri:regionArea>
<wicri:noRegion>Taipei</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Liao, Fong" sort="Liao, Fong" uniqKey="Liao F" first="Fong" last="Liao">Fong Liao</name>
<affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Institute of Biomedical Science, Academia Sinica, Taipei</wicri:regionArea>
<wicri:noRegion>Taipei</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ho, Mei Shang" sort="Ho, Mei Shang" uniqKey="Ho M" first="Mei-Shang" last="Ho">Mei-Shang Ho</name>
<affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Institute of Biomedical Science, Academia Sinica, Taipei</wicri:regionArea>
<wicri:noRegion>Taipei</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Graduate Institute of Epidemiology, National Taiwan University, Taipei</wicri:regionArea>
<wicri:noRegion>Taipei</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><country xml:lang="fr">Taïwan</country>
<wicri:regionArea>Institute of Public Health, National Yang-Ming University, Taipei</wicri:regionArea>
<wicri:noRegion>Taipei</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><country wicri:rule="url">Taïwan</country>
</affiliation>
<affiliation wicri:level="1"><country wicri:rule="url">Taïwan</country>
<wicri:regionArea>Reprints or correspondence: Dr. Mei-Shang Ho, IBMS, Academia Sinica, Taipei</wicri:regionArea>
<wicri:noRegion>Taipei</wicri:noRegion>
</affiliation>
</author>
</analytic>
<monogr></monogr>
<series><title level="j" type="main">Clinical Infectious Diseases</title>
<title level="j" type="abbrev">Clinical Infectious Diseases</title>
<idno type="ISSN">1058-4838</idno>
<idno type="eISSN">1537-6591</idno>
<imprint><publisher>The University of Chicago Press</publisher>
<date type="published">2006</date>
<biblScope unit="vol">42</biblScope>
<biblScope unit="issue">11</biblScope>
<biblScope unit="page" from="1561">1561</biblScope>
<biblScope unit="page" to="1569">1569</biblScope>
</imprint>
<idno type="ISSN">1058-4838</idno>
</series>
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<seriesStmt><idno type="ISSN">1058-4838</idno>
</seriesStmt>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Female</term>
<term>Fibrinogen (genetics)</term>
<term>Humans</term>
<term>Interleukin-1 (genetics)</term>
<term>Interleukin-18 (genetics)</term>
<term>Logistic Models</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Multivariate Analysis</term>
<term>Nasopharynx (virology)</term>
<term>Polymorphism, Genetic</term>
<term>SARS Virus (physiology)</term>
<term>Transcription Factor RelB (genetics)</term>
<term>Viral Load</term>
<term>Virus Shedding (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Analyse multivariée</term>
<term>Charge virale</term>
<term>Excrétion virale (génétique)</term>
<term>Facteur de transcription RelB (génétique)</term>
<term>Femelle</term>
<term>Fibrinogène (génétique)</term>
<term>Humains</term>
<term>Interleukine-1 (génétique)</term>
<term>Interleukine-18 (génétique)</term>
<term>Modèles logistiques</term>
<term>Mâle</term>
<term>Partie nasale du pharynx (virologie)</term>
<term>Polymorphisme génétique</term>
<term>Sujet âgé</term>
<term>Virus du SRAS (physiologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Fibrinogen</term>
<term>Interleukin-1</term>
<term>Interleukin-18</term>
<term>Transcription Factor RelB</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Virus Shedding</term>
</keywords>
<keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Excrétion virale</term>
<term>Facteur de transcription RelB</term>
<term>Fibrinogène</term>
<term>Interleukine-1</term>
<term>Interleukine-18</term>
</keywords>
<keywords scheme="MESH" qualifier="physiologie" xml:lang="fr"><term>Virus du SRAS</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>SARS Virus</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Partie nasale du pharynx</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>Nasopharynx</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Female</term>
<term>Humans</term>
<term>Logistic Models</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Multivariate Analysis</term>
<term>Polymorphism, Genetic</term>
<term>Viral Load</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Analyse multivariée</term>
<term>Charge virale</term>
<term>Femelle</term>
<term>Humains</term>
<term>Modèles logistiques</term>
<term>Mâle</term>
<term>Polymorphisme génétique</term>
<term>Sujet âgé</term>
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<front><div type="abstract">Background. A high initial or peak severe acute respiratory syndrome (SARS)—associated coronavirus (SARS-CoV) load in nasopharyngeal specimens was shown to be associated with a high mortality rate. Because all infected individuals were devoid of preeexisting protective immunity against SARS-CoV, the biological basis for the variable virus burdens in different patients remains elusive. Methods. The nationwide SARS database in Taiwan was analyzed, and genotyping of 281 single-nucleotide polymorphisms (SNPs) of 65 genes was performed for 94 patients with SARS, to identify SNPs for which distribution between patients with or without detectable nasopharyngeal shedding of SARS-CoV was biased. Results. Titers of SARS-CoV shed in nasopharyngeal specimens varied widely, ranging from nondetectable to 108 SARS-CoV RNA copies/mL, and they were correlated positively with a high mortality rate (P < .0001, by trend test) and with early death (i.e., death occurring within 2 weeks of the onset of illness) (P = .0015, by trend test). Virus shedding was found to be higher among male patients (P = .0014, by multivariate logistic regression) and among older patients (P = .015, by multivariate logistic regression). Detectable nasopharyngeal shedding of SARS-CoV was associated with polymorphic alleles of interleukins 18 (P = .014) and 1A (P = .031) and a member of NFκB complex (reticuloendotheliosis viral oncogene homolog B [RelB]) (P = .034), all of which are proinflammatory in nature, as well as the procoagulation molecule fibrinogen-like protein 2 (P = .008). Conclusion. The SARS-CoV load is a determinant of clinical outcomes of SARS, and it is associated with polymorphisms of genes involved in innate immunity, which might be regulated in an age- and sex-dependent manner. The findings of the present study provided leads to genes involved in the host response to SARS-CoV infection; if substantiated with functional studies, these findings may be applicable to other newly emerged respiratory viruses (e.g., the influenza pandemic strain).</div>
</front>
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