Serveur d'exploration MERS

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Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity

Identifieur interne : 000C18 ( Pmc/Checkpoint ); précédent : 000C17; suivant : 000C19

Comparative and kinetic analysis of viral shedding and immunological responses in MERS patients representing a broad spectrum of disease severity

Auteurs : Chan-Ki Min ; Shinhye Cheon [Corée du Sud] ; Na-Young Ha ; Kyung Mok Sohn [Corée du Sud] ; Yuri Kim ; Abdimadiyeva Aigerim ; Hyun Mu Shin ; Ji-Yeob Choi ; Kyung-Soo Inn ; Jin-Hwan Kim [Corée du Sud] ; Jae Young Moon [Corée du Sud] ; Myung-Sik Choi ; Nam-Hyuk Cho ; Yeon-Sook Kim [Corée du Sud]

Source :

RBID : PMC:4857172

Abstract

Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS.

Supplementary information

The online version of this article (doi:10.1038/srep25359) contains supplementary material, which is available to authorized users.


Url:
DOI: 10.1038/srep25359
PubMed: 27146253
PubMed Central: 4857172


Affiliations:


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PMC:4857172

Le document en format XML

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<p id="Par1">Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS.</p>
<sec>
<title>Supplementary information</title>
<p>The online version of this article (doi:10.1038/srep25359) contains supplementary material, which is available to authorized users.</p>
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<name>
<surname>Min</surname>
<given-names>Chan-Ki</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff2">2</xref>
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<name>
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<xref ref-type="aff" rid="Aff3">3</xref>
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<surname>Ha</surname>
<given-names>Na-Young</given-names>
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<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff2">2</xref>
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<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Sohn</surname>
<given-names>Kyung Mok</given-names>
</name>
<xref ref-type="aff" rid="Aff3">3</xref>
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<contrib contrib-type="author">
<name>
<surname>Kim</surname>
<given-names>Yuri</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff2">2</xref>
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<contrib contrib-type="author">
<name>
<surname>Aigerim</surname>
<given-names>Abdimadiyeva</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Shin</surname>
<given-names>Hyun Mu</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff2">2</xref>
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<name>
<surname>Choi</surname>
<given-names>Ji-Yeob</given-names>
</name>
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<name>
<surname>Inn</surname>
<given-names>Kyung-Soo</given-names>
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<name>
<surname>Kim</surname>
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<name>
<surname>Moon</surname>
<given-names>Jae Young</given-names>
</name>
<xref ref-type="aff" rid="Aff7">7</xref>
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<contrib contrib-type="author">
<name>
<surname>Choi</surname>
<given-names>Myung-Sik</given-names>
</name>
<xref ref-type="aff" rid="Aff1">1</xref>
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<contrib contrib-type="author" corresp="yes">
<name>
<surname>Cho</surname>
<given-names>Nam-Hyuk</given-names>
</name>
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<email>chonh@snu.ac.kr</email>
</address>
<xref ref-type="aff" rid="Aff1">1</xref>
<xref ref-type="aff" rid="Aff2">2</xref>
<xref ref-type="aff" rid="Aff8">8</xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Kim</surname>
<given-names>Yeon-Sook</given-names>
</name>
<address>
<email>alice@cnuh.co.kr</email>
</address>
<xref ref-type="aff" rid="Aff3">3</xref>
</contrib>
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Seoul Republic of Korea</aff>
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<pub-date pub-type="epub">
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<month>5</month>
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<year>2016</year>
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<history>
<date date-type="received">
<day>2</day>
<month>3</month>
<year>2016</year>
</date>
<date date-type="accepted">
<day>15</day>
<month>4</month>
<year>2016</year>
</date>
</history>
<permissions>
<copyright-statement>© The Author(s) 2016</copyright-statement>
<license license-type="OpenAccess">
<license-p>This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit
<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by/4.0/">http://creativecommons.org/licenses/by/4.0/</ext-link>
</license-p>
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<abstract id="Abs1">
<p id="Par1">Despite the ongoing spread of MERS, there is limited knowledge of the factors affecting its severity and outcomes. We analyzed clinical data and specimens from fourteen MERS patients treated in a hospital who collectively represent a wide spectrum of disease severity, ranging from mild febrile illness to fatal pneumonia, and classified the patients into four groups based on severity and mortality. Comparative and kinetic analyses revealed that high viral loads, weak antibody responses, and lymphopenia accompanying thrombocytopenia were associated with disease mortality, whereas persistent and gradual increases in lymphocyte responses might be required for effective immunity against MERS-CoV infection. Leukocytosis, primarily due to increased neutrophils and monocytes, was generally observed in more severe and fatal cases. The blood levels of cytokines such as IL-10, IL-15, TGF-β, and EGF were either positively or negatively correlated with disease mortality. Robust induction of various chemokines with differential kinetics was more prominent in patients that recovered from pneumonia than in patients with mild febrile illness or deceased patients. The correlation of the virological and immunological responses with disease severity and mortality, as well as their responses to current antiviral therapy, may have prognostic significance during the early phase of MERS.</p>
<sec>
<title>Supplementary information</title>
<p>The online version of this article (doi:10.1038/srep25359) contains supplementary material, which is available to authorized users.</p>
</sec>
</abstract>
<kwd-group kwd-group-type="npg-subject">
<title>Subject terms</title>
<kwd>SARS virus</kwd>
<kwd>Viral host response</kwd>
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<custom-meta-group>
<custom-meta>
<meta-name>issue-copyright-statement</meta-name>
<meta-value>© The Author(s) 2016</meta-value>
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</front>
</pmc>
<affiliations>
<list>
<country>
<li>Corée du Sud</li>
</country>
</list>
<tree>
<noCountry>
<name sortKey="Aigerim, Abdimadiyeva" sort="Aigerim, Abdimadiyeva" uniqKey="Aigerim A" first="Abdimadiyeva" last="Aigerim">Abdimadiyeva Aigerim</name>
<name sortKey="Cho, Nam Hyuk" sort="Cho, Nam Hyuk" uniqKey="Cho N" first="Nam-Hyuk" last="Cho">Nam-Hyuk Cho</name>
<name sortKey="Choi, Ji Yeob" sort="Choi, Ji Yeob" uniqKey="Choi J" first="Ji-Yeob" last="Choi">Ji-Yeob Choi</name>
<name sortKey="Choi, Myung Sik" sort="Choi, Myung Sik" uniqKey="Choi M" first="Myung-Sik" last="Choi">Myung-Sik Choi</name>
<name sortKey="Ha, Na Young" sort="Ha, Na Young" uniqKey="Ha N" first="Na-Young" last="Ha">Na-Young Ha</name>
<name sortKey="Inn, Kyung Soo" sort="Inn, Kyung Soo" uniqKey="Inn K" first="Kyung-Soo" last="Inn">Kyung-Soo Inn</name>
<name sortKey="Kim, Yuri" sort="Kim, Yuri" uniqKey="Kim Y" first="Yuri" last="Kim">Yuri Kim</name>
<name sortKey="Min, Chan Ki" sort="Min, Chan Ki" uniqKey="Min C" first="Chan-Ki" last="Min">Chan-Ki Min</name>
<name sortKey="Shin, Hyun Mu" sort="Shin, Hyun Mu" uniqKey="Shin H" first="Hyun Mu" last="Shin">Hyun Mu Shin</name>
</noCountry>
<country name="Corée du Sud">
<noRegion>
<name sortKey="Cheon, Shinhye" sort="Cheon, Shinhye" uniqKey="Cheon S" first="Shinhye" last="Cheon">Shinhye Cheon</name>
</noRegion>
<name sortKey="Kim, Jin Hwan" sort="Kim, Jin Hwan" uniqKey="Kim J" first="Jin-Hwan" last="Kim">Jin-Hwan Kim</name>
<name sortKey="Kim, Yeon Sook" sort="Kim, Yeon Sook" uniqKey="Kim Y" first="Yeon-Sook" last="Kim">Yeon-Sook Kim</name>
<name sortKey="Moon, Jae Young" sort="Moon, Jae Young" uniqKey="Moon J" first="Jae Young" last="Moon">Jae Young Moon</name>
<name sortKey="Sohn, Kyung Mok" sort="Sohn, Kyung Mok" uniqKey="Sohn K" first="Kyung Mok" last="Sohn">Kyung Mok Sohn</name>
</country>
</tree>
</affiliations>
</record>

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