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Nasopharyngeal shedding of severe acute respiratory syndrome-associated coronavirus is associated with genetic polymorphisms

Identifieur interne : 000449 ( PascalFrancis/Checkpoint ); précédent : 000448; suivant : 000450

Nasopharyngeal 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 :

RBID : Pascal:06-0348647

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English descriptors

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).


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Pascal:06-0348647

Le document en format XML

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<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>
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<s1>HO (Mei-Shang)</s1>
</fA11>
<fA14 i1="01">
<s1>Institute of Biomedical Science, Academia Sinica, National Taiwan University</s1>
<s3>TWN</s3>
<sZ>1 aut.</sZ>
<sZ>4 aut.</sZ>
<sZ>5 aut.</sZ>
<sZ>10 aut.</sZ>
<sZ>11 aut.</sZ>
</fA14>
<fA14 i1="02">
<s1>Center for Disease Control, National Taiwan University</s1>
<s3>TWN</s3>
<sZ>2 aut.</sZ>
<sZ>3 aut.</sZ>
<sZ>8 aut.</sZ>
<sZ>9 aut.</sZ>
</fA14>
<fA14 i1="03">
<s1>Graduate Institute of Epidemiology, National Taiwan University</s1>
<s3>TWN</s3>
<sZ>6 aut.</sZ>
<sZ>11 aut.</sZ>
</fA14>
<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>
</fA14>
<fA20>
<s1>1561-1569</s1>
</fA20>
<fA21>
<s1>2006</s1>
</fA21>
<fA23 i1="01">
<s0>ENG</s0>
</fA23>
<fA43 i1="01">
<s1>INIST</s1>
<s2>18407</s2>
<s5>354000142370600070</s5>
</fA43>
<fA44>
<s0>0000</s0>
<s1>© 2006 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45>
<s0>46 ref.</s0>
</fA45>
<fA47 i1="01" i2="1">
<s0>06-0348647</s0>
</fA47>
<fA60>
<s1>P</s1>
</fA60>
<fA61>
<s0>A</s0>
</fA61>
<fA64 i1="01" i2="1">
<s0>Clinical infectious diseases</s0>
</fA64>
<fA66 i1="01">
<s0>USA</s0>
</fA66>
<fC01 i1="01" l="ENG">
<s0>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).</s0>
</fC01>
<fC02 i1="01" i2="X">
<s0>002B05C02C</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE">
<s0>Syndrome respiratoire aigu sévère</s0>
<s2>NM</s2>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG">
<s0>Severe acute respiratory syndrome</s0>
<s2>NM</s2>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA">
<s0>Síndrome respiratorio agudo severo</s0>
<s2>NM</s2>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE">
<s0>Nasopharynx</s0>
<s5>07</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG">
<s0>Nasopharynx</s0>
<s5>07</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA">
<s0>Nasofaringe</s0>
<s5>07</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE">
<s0>Polymorphisme</s0>
<s5>08</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG">
<s0>Polymorphism</s0>
<s5>08</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA">
<s0>Polimorfismo</s0>
<s5>08</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE">
<s0>Coronavirus</s0>
<s2>NW</s2>
<s5>10</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG">
<s0>Coronavirus</s0>
<s2>NW</s2>
<s5>10</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA">
<s0>Coronavirus</s0>
<s2>NW</s2>
<s5>10</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE">
<s0>Virose</s0>
</fC07>
<fC07 i1="01" i2="X" l="ENG">
<s0>Viral disease</s0>
</fC07>
<fC07 i1="01" i2="X" l="SPA">
<s0>Virosis</s0>
</fC07>
<fC07 i1="02" i2="X" l="FRE">
<s0>Infection</s0>
</fC07>
<fC07 i1="02" i2="X" l="ENG">
<s0>Infection</s0>
</fC07>
<fC07 i1="02" i2="X" l="SPA">
<s0>Infección</s0>
</fC07>
<fC07 i1="03" i2="X" l="FRE">
<s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG">
<s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA">
<s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="FRE">
<s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="ENG">
<s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="04" i2="X" l="SPA">
<s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="FRE">
<s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="ENG">
<s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="05" i2="X" l="SPA">
<s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="06" i2="X" l="FRE">
<s0>Appareil respiratoire pathologie</s0>
<s5>37</s5>
</fC07>
<fC07 i1="06" i2="X" l="ENG">
<s0>Respiratory disease</s0>
<s5>37</s5>
</fC07>
<fC07 i1="06" i2="X" l="SPA">
<s0>Aparato respiratorio patología</s0>
<s5>37</s5>
</fC07>
<fC07 i1="07" i2="X" l="FRE">
<s0>Poumon pathologie</s0>
<s5>38</s5>
</fC07>
<fC07 i1="07" i2="X" l="ENG">
<s0>Lung disease</s0>
<s5>38</s5>
</fC07>
<fC07 i1="07" i2="X" l="SPA">
<s0>Pulmón patología</s0>
<s5>38</s5>
</fC07>
<fN21>
<s1>227</s1>
</fN21>
<fN44 i1="01">
<s1>OTO</s1>
</fN44>
<fN82>
<s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
<affiliations>
<list>
<country>
<li>Taïwan</li>
</country>
</list>
<tree>
<country name="Taïwan">
<noRegion>
<name sortKey="Chen, Wei Ju" sort="Chen, Wei Ju" uniqKey="Chen W" first="Wei-Ju" last="Chen">Wei-Ju Chen</name>
</noRegion>
<name sortKey="Chang, Hsiao Ling" sort="Chang, Hsiao Ling" uniqKey="Chang H" first="Hsiao-Ling" last="Chang">Hsiao-Ling Chang</name>
<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>
<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>
<name sortKey="Fong Liao" sort="Fong Liao" uniqKey="Fong Liao" last="Fong Liao">FONG LIAO</name>
<name sortKey="Ho, Mei Shang" sort="Ho, Mei Shang" uniqKey="Ho M" first="Mei-Shang" last="Ho">Mei-Shang Ho</name>
<name sortKey="Ho, Mei Shang" sort="Ho, Mei Shang" uniqKey="Ho M" first="Mei-Shang" last="Ho">Mei-Shang Ho</name>
<name sortKey="Ho, Mei Shang" sort="Ho, Mei Shang" uniqKey="Ho M" first="Mei-Shang" last="Ho">Mei-Shang Ho</name>
<name sortKey="King, Chwan Chuen" sort="King, Chwan Chuen" uniqKey="King C" first="Chwan-Chuen" last="King">Chwan-Chuen King</name>
<name sortKey="Kuo, Hung Wei" sort="Kuo, Hung Wei" uniqKey="Kuo H" first="Hung-Wei" last="Kuo">Hung-Wei Kuo</name>
<name sortKey="Lin, Jih Hui" sort="Lin, Jih Hui" uniqKey="Lin J" first="Jih-Hui" last="Lin">Jih-Hui Lin</name>
<name sortKey="Osyetrov, Valeriy" sort="Osyetrov, Valeriy" uniqKey="Osyetrov V" first="Valeriy" last="Osyetrov">Valeriy Osyetrov</name>
<name sortKey="Yang, Jyh Yuan" sort="Yang, Jyh Yuan" uniqKey="Yang J" first="Jyh-Yuan" last="Yang">Jyh-Yuan Yang</name>
</country>
</tree>
</affiliations>
</record>

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