Serveur d'exploration MERS

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Comparative Serological Study for the Prevalence of Anti-MERS Coronavirus Antibodies in High- and Low-Risk Groups in Qatar

Identifieur interne : 000E14 ( Pmc/Curation ); précédent : 000E13; suivant : 000E15

Comparative Serological Study for the Prevalence of Anti-MERS Coronavirus Antibodies in High- and Low-Risk Groups in Qatar

Auteurs : Reham A. Al Kahlout [Qatar] ; Gheyath K. Nasrallah [Qatar] ; Elmoubasher A. Farag [Qatar] ; Lingshu Wang [États-Unis] ; Erik Lattwein [Allemagne] ; Marcel A. Müller [Allemagne] ; Mohamed E. El Zowalaty [Afrique du Sud] ; Hamad E. Al Romaihi [Qatar] ; Barney S. Graham [États-Unis] ; Asmaa A. Al Thani [Qatar] ; Hadi M. Yassine [Qatar]

Source :

RBID : PMC:6398027

Abstract

Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) could be asymptomatic or cause mild influenza-like illness. Therefore, the prevalence of MERS-CoV infections in the general population could be underestimated, which necessitates active surveillance to determine the epidemiological importance of asymptomatic cases. The aim of this study is to evaluate the performance of various serological assays and to estimate the seroprevalence of anti-MERS-CoV antibodies in high- and low-risk groups in Qatar. A total of 4858 samples were screened, including 4719 samples collected from healthy blood donors (BD) over a period of five years (2012-2016), 135 samples from baseline case contacts (CC) collected from individuals in close contact with three positive PCR-confirmed patients (CP), and four samples from MERS-CoV CP. Initial screening using anti-MERS-CoV IgG (IgG rS1-ELISA kit) revealed ten reactive samples from BD (10/4719, 0.21%), one from CC (1/135, 0.74%), and three from CP (3/4, 75%). Samples from CP but not from BD were also reactive by whole-virus anti-MERS-CoV IgG (n = 3/4) and IgM (n = 1/4) indirect immunefluorescent tests (IIFT) and pseudoparticle neutralization test (ppNT). The reactive sample from CC was also confirmed by ppNT. Surprisingly, one out of thirteen (7.7%) randomly selected IgG rS1-ELISA-negative BD samples from the initial screening was reactive by the IgM-IIFT (but not by the IgG-IIFT) and was subsequently confirmed by ppNT. All IgG rS1-ELISA-reactive samples from BD exhibited considerable reactivity to the four circulating human coronaviruses (HKU1, OC43, 229E, and NL63). Cross-reactivity with SARS was only reported for samples from CP using IgG and IgM-IIFT. In conclusion, we report a low prevalence of anti-MERS antibodies in the general population, which coincides with the low number of all reported cases by the time of our study (2017) in Qatar (n = 21). The false-positive results and the observed cross-reactivity between MERS-CoV and other circulating human coronavirus necessitate more detailed evaluation of available serological assays.


Url:
DOI: 10.1155/2019/1386740
PubMed: 30906787
PubMed Central: 6398027

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PMC:6398027

Le document en format XML

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<name sortKey="Yassine, Hadi M" sort="Yassine, Hadi M" uniqKey="Yassine H" first="Hadi M." last="Yassine">Hadi M. Yassine</name>
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<p>Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) could be asymptomatic or cause mild influenza-like illness. Therefore, the prevalence of MERS-CoV infections in the general population could be underestimated, which necessitates active surveillance to determine the epidemiological importance of asymptomatic cases. The aim of this study is to evaluate the performance of various serological assays and to estimate the seroprevalence of anti-MERS-CoV antibodies in high- and low-risk groups in Qatar. A total of 4858 samples were screened, including 4719 samples collected from healthy blood donors (BD) over a period of five years (2012-2016), 135 samples from baseline case contacts (CC) collected from individuals in close contact with three positive PCR-confirmed patients (CP), and four samples from MERS-CoV CP. Initial screening using anti-MERS-CoV IgG (IgG rS1-ELISA kit) revealed ten reactive samples from BD (10/4719, 0.21%), one from CC (1/135, 0.74%), and three from CP (3/4, 75%). Samples from CP but not from BD were also reactive by whole-virus anti-MERS-CoV IgG (
<italic>n</italic>
= 3/4) and IgM (
<italic>n</italic>
= 1/4) indirect immunefluorescent tests (IIFT) and pseudoparticle neutralization test (ppNT). The reactive sample from CC was also confirmed by ppNT. Surprisingly, one out of thirteen (7.7%) randomly selected IgG rS1-ELISA-negative BD samples from the initial screening was reactive by the IgM-IIFT (but not by the IgG-IIFT) and was subsequently confirmed by ppNT. All IgG rS1-ELISA-reactive samples from BD exhibited considerable reactivity to the four circulating human coronaviruses (HKU1, OC43, 229E, and NL63). Cross-reactivity with SARS was only reported for samples from CP using IgG and IgM-IIFT. In conclusion, we report a low prevalence of anti-MERS antibodies in the general population, which coincides with the low number of all reported cases by the time of our study (2017) in Qatar (
<italic>n</italic>
= 21). The false-positive results and the observed cross-reactivity between MERS-CoV and other circulating human coronavirus necessitate more detailed evaluation of available serological assays.</p>
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</TEI>
<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">J Immunol Res</journal-id>
<journal-id journal-id-type="iso-abbrev">J Immunol Res</journal-id>
<journal-id journal-id-type="publisher-id">JIR</journal-id>
<journal-title-group>
<journal-title>Journal of Immunology Research</journal-title>
</journal-title-group>
<issn pub-type="ppub">2314-8861</issn>
<issn pub-type="epub">2314-7156</issn>
<publisher>
<publisher-name>Hindawi</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">30906787</article-id>
<article-id pub-id-type="pmc">6398027</article-id>
<article-id pub-id-type="doi">10.1155/2019/1386740</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Comparative Serological Study for the Prevalence of Anti-MERS Coronavirus Antibodies in High- and Low-Risk Groups in Qatar</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Al Kahlout</surname>
<given-names>Reham A.</given-names>
</name>
<xref ref-type="aff" rid="I1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author" equal-contrib="yes">
<name>
<surname>Nasrallah</surname>
<given-names>Gheyath K.</given-names>
</name>
<xref ref-type="aff" rid="I1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="I2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Farag</surname>
<given-names>Elmoubasher A.</given-names>
</name>
<xref ref-type="aff" rid="I3">
<sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wang</surname>
<given-names>Lingshu</given-names>
</name>
<xref ref-type="aff" rid="I4">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lattwein</surname>
<given-names>Erik</given-names>
</name>
<xref ref-type="aff" rid="I5">
<sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Müller</surname>
<given-names>Marcel A.</given-names>
</name>
<xref ref-type="aff" rid="I6">
<sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0002-1056-4761</contrib-id>
<name>
<surname>El Zowalaty</surname>
<given-names>Mohamed E.</given-names>
</name>
<xref ref-type="aff" rid="I7">
<sup>7</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Al Romaihi</surname>
<given-names>Hamad E.</given-names>
</name>
<xref ref-type="aff" rid="I3">
<sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Graham</surname>
<given-names>Barney S.</given-names>
</name>
<xref ref-type="aff" rid="I4">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Al Thani</surname>
<given-names>Asmaa A.</given-names>
</name>
<xref ref-type="aff" rid="I1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="I2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0001-7592-2788</contrib-id>
<name>
<surname>Yassine</surname>
<given-names>Hadi M.</given-names>
</name>
<email>hyassine@qu.edu.qa</email>
<xref ref-type="aff" rid="I1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="I2">
<sup>2</sup>
</xref>
</contrib>
</contrib-group>
<aff id="I1">
<sup>1</sup>
Department of Biomedical Sciences, College of Health Sciences, Qatar University, Doha, Qatar</aff>
<aff id="I2">
<sup>2</sup>
Biomedical Research Center, Qatar University, Doha, Qatar</aff>
<aff id="I3">
<sup>3</sup>
Communicable Diseases Control Programs, Public Health Department, Ministry of Public Health, Doha, Qatar</aff>
<aff id="I4">
<sup>4</sup>
Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institute of Health, Bethesda, MD, USA</aff>
<aff id="I5">
<sup>5</sup>
Euroimmun AG, Luebeck, Germany</aff>
<aff id="I6">
<sup>6</sup>
Institute of Virology, Charité - Universitätsmedizin Berlin, Charitéplatz 1, Berlin, Germany</aff>
<aff id="I7">
<sup>7</sup>
Virology and Microbiology Research Laboratory, School of Health Sciences, College of Health Sciences, University of KwaZulu-Natal, Westville Campus, Durban 4000, South Africa</aff>
<author-notes>
<fn fn-type="other">
<p>Academic Editor: Peirong Jiao</p>
</fn>
</author-notes>
<pub-date pub-type="collection">
<year>2019</year>
</pub-date>
<pub-date pub-type="epub">
<day>18</day>
<month>2</month>
<year>2019</year>
</pub-date>
<volume>2019</volume>
<elocation-id>1386740</elocation-id>
<history>
<date date-type="received">
<day>3</day>
<month>9</month>
<year>2018</year>
</date>
<date date-type="rev-recd">
<day>29</day>
<month>11</month>
<year>2018</year>
</date>
<date date-type="accepted">
<day>27</day>
<month>12</month>
<year>2018</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2019 Reham A. Al Kahlout et al.</copyright-statement>
<copyright-year>2019</copyright-year>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<license-p>This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
</license>
</permissions>
<abstract>
<p>Infection with Middle East respiratory syndrome coronavirus (MERS-CoV) could be asymptomatic or cause mild influenza-like illness. Therefore, the prevalence of MERS-CoV infections in the general population could be underestimated, which necessitates active surveillance to determine the epidemiological importance of asymptomatic cases. The aim of this study is to evaluate the performance of various serological assays and to estimate the seroprevalence of anti-MERS-CoV antibodies in high- and low-risk groups in Qatar. A total of 4858 samples were screened, including 4719 samples collected from healthy blood donors (BD) over a period of five years (2012-2016), 135 samples from baseline case contacts (CC) collected from individuals in close contact with three positive PCR-confirmed patients (CP), and four samples from MERS-CoV CP. Initial screening using anti-MERS-CoV IgG (IgG rS1-ELISA kit) revealed ten reactive samples from BD (10/4719, 0.21%), one from CC (1/135, 0.74%), and three from CP (3/4, 75%). Samples from CP but not from BD were also reactive by whole-virus anti-MERS-CoV IgG (
<italic>n</italic>
= 3/4) and IgM (
<italic>n</italic>
= 1/4) indirect immunefluorescent tests (IIFT) and pseudoparticle neutralization test (ppNT). The reactive sample from CC was also confirmed by ppNT. Surprisingly, one out of thirteen (7.7%) randomly selected IgG rS1-ELISA-negative BD samples from the initial screening was reactive by the IgM-IIFT (but not by the IgG-IIFT) and was subsequently confirmed by ppNT. All IgG rS1-ELISA-reactive samples from BD exhibited considerable reactivity to the four circulating human coronaviruses (HKU1, OC43, 229E, and NL63). Cross-reactivity with SARS was only reported for samples from CP using IgG and IgM-IIFT. In conclusion, we report a low prevalence of anti-MERS antibodies in the general population, which coincides with the low number of all reported cases by the time of our study (2017) in Qatar (
<italic>n</italic>
= 21). The false-positive results and the observed cross-reactivity between MERS-CoV and other circulating human coronavirus necessitate more detailed evaluation of available serological assays.</p>
</abstract>
<funding-group>
<award-group>
<funding-source>Qatar University</funding-source>
<award-id>QUUG-BRC-2017-1</award-id>
<award-id>QUST-CAS-FALL-15/16-33</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
<floats-group>
<fig id="fig1" orientation="portrait" position="float">
<label>Figure 1</label>
<caption>
<p>Number of reactive samples using rS1-ELISA (IgG) screening. A total of 4858 plasma samples were initially screened for anti-MERS S1 IgG using rS1-ELISA. The graph shows the number of reactive samples in three groups: blood donor (
<italic>n</italic>
= 4719), case contacts (
<italic>n</italic>
= 135), and confirmed cases (
<italic>n</italic>
= 4).</p>
</caption>
<graphic xlink:href="JIR2019-1386740.001"></graphic>
</fig>
<table-wrap id="tab1" orientation="portrait" position="float">
<label>Table 1</label>
<caption>
<p>Characteristic profile of the study population.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th rowspan="2" colspan="1"></th>
<th align="center" colspan="3" rowspan="1">BD (2012-2016)</th>
<th align="center" colspan="3" rowspan="1">CC (2015-2016)</th>
<th align="center" colspan="3" rowspan="1">CP (2015-2016)</th>
</tr>
<tr>
<th align="center" rowspan="1" colspan="1">Number</th>
<th align="center" rowspan="1" colspan="1">Age range (mean)</th>
<th align="center" rowspan="1" colspan="1">Exposure</th>
<th align="center" rowspan="1" colspan="1">Number</th>
<th align="center" rowspan="1" colspan="1">Age range (mean)</th>
<th align="center" rowspan="1" colspan="1">Exposure (
<italic>n</italic>
)</th>
<th align="center" rowspan="1" colspan="1">Number</th>
<th align="center" rowspan="1" colspan="1">Age range (mean)</th>
<th align="center" rowspan="1" colspan="1">Exposure</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="1" colspan="1">Qatari males</td>
<td align="center" rowspan="1" colspan="1">906</td>
<td align="center" rowspan="4" colspan="1">19-88 (37)</td>
<td align="center" rowspan="4" colspan="1">Unknown</td>
<td align="center" rowspan="1" colspan="1">11</td>
<td align="center" rowspan="4" colspan="1">14-49 (31)</td>
<td align="center" rowspan="4" colspan="1">Family contact (37), healthcare worker (73), camel farm worker (25)</td>
<td align="center" rowspan="1" colspan="1">2</td>
<td align="center" rowspan="4" colspan="1">29-69 (51)</td>
<td align="center" rowspan="4" colspan="1">Camel farm</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Qatari females</td>
<td align="center" rowspan="1" colspan="1">22</td>
<td align="center" rowspan="1" colspan="1">3</td>
<td align="center" rowspan="1" colspan="1">0</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Non-Qatari males</td>
<td align="center" rowspan="1" colspan="1">3736</td>
<td align="center" rowspan="1" colspan="1">93</td>
<td align="center" rowspan="1" colspan="1">2</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Non-Qatari females</td>
<td align="center" rowspan="1" colspan="1">55</td>
<td align="center" rowspan="1" colspan="1">28</td>
<td align="center" rowspan="1" colspan="1">0</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Total</td>
<td align="center" rowspan="1" colspan="1">
<bold>4719</bold>
</td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">
<bold>135</bold>
</td>
<td rowspan="1" colspan="1"></td>
<td rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">
<bold>4</bold>
</td>
<td rowspan="1" colspan="1"></td>
<td align="center" rowspan="1" colspan="1">
<bold>4858</bold>
</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="tab2" orientation="portrait" position="float">
<label>Table 2</label>
<caption>
<p>Number of reactive samples for anti-MERS S1 IgG using rS1-ELISA.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" rowspan="1" colspan="1">Sample source</th>
<th align="center" rowspan="1" colspan="1">Year of collection (no. screened)</th>
<th align="center" rowspan="1" colspan="1">No. borderline/no. screened (%)</th>
<th align="center" rowspan="1" colspan="1">No. reactive/no. screened (%)</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="5" colspan="1">BD</td>
<td align="center" rowspan="1" colspan="1">2012 (120)</td>
<td align="center" rowspan="1" colspan="1">
<italic>1/120 (0.83)</italic>
</td>
<td align="center" rowspan="1" colspan="1">0/120 (0)</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">2013 (28)</td>
<td align="center" rowspan="1" colspan="1">0/28 (0)</td>
<td align="center" rowspan="1" colspan="1">0/28 (0)</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">2014 (611)</td>
<td align="center" rowspan="1" colspan="1">0/611 (0)</td>
<td align="center" rowspan="1" colspan="1">
<italic>1/611 (0.16)</italic>
</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">2015 (3383)</td>
<td align="center" rowspan="1" colspan="1">
<italic>1/3383 (0.03)</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>5/3383 (0.15)</italic>
</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">2016 (577)</td>
<td align="center" rowspan="1" colspan="1">
<italic>1/577 (0.17)</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>1/577 (0.17)</italic>
</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Subtotal</td>
<td align="center" rowspan="1" colspan="1">4719</td>
<td align="center" rowspan="1" colspan="1">
<italic>3/4719 (0.08)</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>7/4719 (0.13)</italic>
</td>
</tr>
<tr>
<td align="left" rowspan="3" colspan="1">CC</td>
<td align="center" rowspan="1" colspan="1">May-2015 (100)</td>
<td align="center" rowspan="1" colspan="1">0/100 (0)</td>
<td align="center" rowspan="1" colspan="1">
<italic>1/100 (1)</italic>
</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">Feb-2016 (10)</td>
<td align="center" rowspan="1" colspan="1">0/10 (0)</td>
<td align="center" rowspan="1" colspan="1">0/10 (0)</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">June-2016 (25)</td>
<td align="center" rowspan="1" colspan="1">0/25 (0)</td>
<td align="center" rowspan="1" colspan="1">0/25 (0)</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Subtotal</td>
<td align="center" rowspan="1" colspan="1">135</td>
<td align="center" rowspan="1" colspan="1">0/135 (0)</td>
<td align="center" rowspan="1" colspan="1">1/135 (0.74)</td>
</tr>
<tr>
<td align="left" rowspan="4" colspan="1">CP</td>
<td align="center" rowspan="1" colspan="1">Mar-2015 (1)</td>
<td align="center" rowspan="1" colspan="1">0/1 (0)</td>
<td align="center" rowspan="1" colspan="1">
<italic>1/1 (100)</italic>
</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">May-2015 (1)</td>
<td align="center" rowspan="1" colspan="1">0/1 (0)</td>
<td align="center" rowspan="1" colspan="1">
<italic>1/1 (100)</italic>
</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">Feb-2016 (1)</td>
<td align="center" rowspan="1" colspan="1">0/1 (0)</td>
<td align="center" rowspan="1" colspan="1">
<italic>1/1 (100)</italic>
</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">May-2016 (1)</td>
<td align="center" rowspan="1" colspan="1">0/1 (0)</td>
<td align="center" rowspan="1" colspan="1">0/1 (0)</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Subtotal</td>
<td align="center" rowspan="1" colspan="1">4</td>
<td align="center" rowspan="1" colspan="1">0/4 (0)</td>
<td align="center" rowspan="1" colspan="1">
<italic>3/4</italic>
(75)</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">Total</td>
<td align="center" rowspan="1" colspan="1">
<bold>Total (4858)</bold>
</td>
<td align="center" rowspan="1" colspan="1">
<bold>3/4858 (0.06)</bold>
</td>
<td align="center" rowspan="1" colspan="1">
<bold>12/4858 (0.25)</bold>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>Positive samples are shown in
<italic>italic</italic>
.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tab3" orientation="portrait" position="float">
<label>Table 3</label>
<caption>
<p>Comparative serological analysis of reactive and borderline samples from blood donors (BD).</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th colspan="2" rowspan="1"></th>
<th align="center" rowspan="1" colspan="1">rS1-ELISA
<sup></sup>
</th>
<th align="center" colspan="2" rowspan="1">Full virus IIFT</th>
<th align="center" rowspan="1" colspan="1">rS1-IIFT</th>
<th align="center" rowspan="1" colspan="1">ppNT</th>
</tr>
<tr>
<th rowspan="1" colspan="1"></th>
<th align="center" rowspan="1" colspan="1">Sample identifier</th>
<th align="center" rowspan="1" colspan="1">IgG (OD, ratio, endpoint titer)</th>
<th align="center" rowspan="1" colspan="1">IgG titer</th>
<th align="center" rowspan="1" colspan="1">IgM titer</th>
<th align="center" rowspan="1" colspan="1">IgG titer</th>
<th align="center" rowspan="1" colspan="1">IC50 titer (EMC/JordanN3)</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="7" colspan="1">Reactive (
<italic>n</italic>
= 7)</td>
<td align="center" rowspan="1" colspan="1">BD 2014/597</td>
<td align="center" rowspan="1" colspan="1">
<italic>(0.905, 2.114, 201)</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1"><50</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">BD 2015/1303</td>
<td align="center" rowspan="1" colspan="1">
<italic>(0.397, 1.3, 101)</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>10000</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1"><50</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">BD 2015/3004</td>
<td align="center" rowspan="1" colspan="1">
<italic>(0.439, 1.26, 201)</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1"><50</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">BD 2015/3119</td>
<td align="center" rowspan="1" colspan="1">
<italic>(0.402, 1.06, 401)</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1"><50</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">BD 2015/3380</td>
<td align="center" rowspan="1" colspan="1">
<italic>(0.477, 1.1, 101)</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>10000</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1"><50</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">BD 2015/3513</td>
<td align="center" rowspan="1" colspan="1">
<italic>(0.497, 1.39, 401)</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1"><50</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">BD 2015/4435</td>
<td align="center" rowspan="1" colspan="1">
<italic>(0.661, 1.74, 201)</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1"><50</td>
</tr>
<tr>
<td align="left" rowspan="3" colspan="1">Borderline (
<italic>n</italic>
= 3)</td>
<td align="center" rowspan="1" colspan="1">BD 2012/2644</td>
<td align="center" rowspan="1" colspan="1">
<italic>(0.333, 0.83, 101)</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1"><50</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">BD 2015/1816</td>
<td align="center" rowspan="1" colspan="1">
<italic>(0.456, 0.823,201)</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1"><50</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">BD 2015/4708</td>
<td align="center" rowspan="1" colspan="1">
<italic>(0.408, 1.07, 101)</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1"><50</td>
</tr>
<tr>
<td align="left" rowspan="3" colspan="1">Selected negative (showing 3/13)
<sup>∗∗</sup>
</td>
<td align="center" rowspan="1" colspan="1">BD 2015/2859</td>
<td align="center" rowspan="1" colspan="1">(0.034, 0.076, <101)</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1"><50</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">BD 2015/2988</td>
<td align="center" rowspan="1" colspan="1">(0.039, 0.112, <101)</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1"><50</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">BD 2015/3379</td>
<td align="center" rowspan="1" colspan="1">(0.065, 0. 16, <101)</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>531/502</italic>
</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>
<sup></sup>
Initial screening was done with rS1-ELISA, and reactive samples were further tested with various serological assays as indicated above.
<sup>∗∗</sup>
13 negative samples from the initial screening with rS1-ELISA were selected for comparison, and one was found positive with full virus IgM and ppNT. Positive samples are shown in
<italic>italic</italic>
.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tab4" orientation="portrait" position="float">
<label>Table 4</label>
<caption>
<p>Comparative serological analysis of reactive samples from CC and CP.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th rowspan="1" colspan="1"></th>
<th align="center" rowspan="1" colspan="1">rS1-ELISA</th>
<th align="center" colspan="2" rowspan="1">Full virus IIFT</th>
<th align="center" rowspan="1" colspan="1">rS1-IIFT</th>
<th align="center" rowspan="1" colspan="1">ppNT</th>
</tr>
<tr>
<th align="left" rowspan="1" colspan="1">Sample identifier</th>
<th align="center" rowspan="1" colspan="1">IgG (OD, ratio, endpoint titer)</th>
<th align="center" rowspan="1" colspan="1">IgG titer</th>
<th align="center" rowspan="1" colspan="1">IgM titer</th>
<th align="center" rowspan="1" colspan="1">IgG titer</th>
<th align="center" rowspan="1" colspan="1">IC50 titer (EMC/JordanN3)</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="1" colspan="1">CC May.2015</td>
<td align="center" rowspan="1" colspan="1">
<italic>(0.61, 1.5, 101)</italic>
</td>
<td align="center" rowspan="1" colspan="1">Quantity not sufficient</td>
<td align="center" rowspan="1" colspan="1">Quantity not sufficient</td>
<td align="center" rowspan="1" colspan="1">Quantity not sufficient</td>
<td align="center" rowspan="1" colspan="1">
<italic>76/149</italic>
</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">CP Mar.2015</td>
<td align="center" rowspan="1" colspan="1">
<italic>(1.084, 2.86, 201)</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>10000</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>>10000</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>630/1707</italic>
</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">CP May.2015</td>
<td align="center" rowspan="1" colspan="1">
<italic>(0.412, 1.37, ND
<sup></sup>
)</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>199/688</italic>
</td>
</tr>
<tr>
<td align="left" rowspan="1" colspan="1">CP Feb.2016</td>
<td align="center" rowspan="1" colspan="1">
<italic>(2.229, 6.517, ≥ 3201)</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>>32000</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>100</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>>10000</italic>
</td>
<td align="center" rowspan="1" colspan="1">ND</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>Positive samples are shown in
<italic>italic</italic>
. ND: not determined.
<sup></sup>
This samples showed controversial results in rS1-ELISA IgG and was considered positive based on IIFT.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="tab5" orientation="portrait" position="float">
<label>Table 5</label>
<caption>
<p>Cross-reactivity of reactive samples with rS1-ELISA and other human coronaviruses.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th rowspan="2" colspan="1"></th>
<th align="center" rowspan="2" colspan="1">Sample identifier</th>
<th align="center" colspan="2" rowspan="1">Whole-virus IIFT IgG titer</th>
<th align="center" rowspan="1" colspan="1">rS1-ELISA titer IgG</th>
<th align="center" colspan="5" rowspan="1">rS1-IIFT titer IgG</th>
</tr>
<tr>
<th align="center" rowspan="1" colspan="1">229E</th>
<th align="center" rowspan="1" colspan="1">SARS</th>
<th align="center" rowspan="1" colspan="1">HKU1</th>
<th align="center" rowspan="1" colspan="1">229E</th>
<th align="center" rowspan="1" colspan="1">OC43</th>
<th align="center" rowspan="1" colspan="1">SARS</th>
<th align="center" rowspan="1" colspan="1">NL63</th>
<th align="center" rowspan="1" colspan="1">HKU1</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" rowspan="7" colspan="1">Reactive BD</td>
<td align="center" rowspan="1" colspan="1">BD 2014/597</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥320</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥100</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">BD 2015/1303</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥101</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">BD 2015/3004</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥1000</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥101</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">BD 2015/3119</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥320</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥101</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">BD 2015/3380</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥101</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">BD 2015/3513</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥1000</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥101</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">BD 2015/4435</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥320</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥101</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
</tr>
<tr>
<td align="left" rowspan="3" colspan="1">Borderline BD</td>
<td align="center" rowspan="1" colspan="1">BD 2012/2644</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥1000</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥101</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">BD 2015/1816</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥320</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥101</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">BD 2015/4708</td>
<td align="center" rowspan="1" colspan="1">ND</td>
<td align="center" rowspan="1" colspan="1">ND</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥101</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
</tr>
<tr>
<td align="left" rowspan="3" colspan="1">Selected negative BD (showing 3/13)</td>
<td align="center" rowspan="1" colspan="1">BD 2015/2859</td>
<td align="center" rowspan="1" colspan="1">ND</td>
<td align="center" rowspan="1" colspan="1">ND</td>
<td align="center" rowspan="1" colspan="1">ND</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">BD 2015/2988</td>
<td align="center" rowspan="1" colspan="1">ND</td>
<td align="center" rowspan="1" colspan="1">ND</td>
<td align="center" rowspan="1" colspan="1">ND</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">BD 2015/3379</td>
<td align="center" rowspan="1" colspan="1">
<italic>320 (IgM = 0)</italic>
</td>
<td align="center" rowspan="1" colspan="1">0 (IgM = 0)</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥101</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
</tr>
<tr>
<td align="left" rowspan="3" colspan="1">Reactive CP</td>
<td align="center" rowspan="1" colspan="1">CP Mar.2015</td>
<td align="center" rowspan="1" colspan="1">
<italic>100</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥101</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">CP May.2015</td>
<td align="center" rowspan="1" colspan="1">
<italic>1000</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥101</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>320</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
</tr>
<tr>
<td align="center" rowspan="1" colspan="1">CP Feb.2016</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">
<italic>1000</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>≥101</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>>10000</italic>
</td>
<td align="center" rowspan="1" colspan="1">
<italic>3200</italic>
</td>
<td align="center" rowspan="1" colspan="1">0</td>
<td align="center" rowspan="1" colspan="1">0</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn>
<p>Positive samples are shown in
<italic>italic</italic>
. ND: not determined.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</floats-group>
</pmc>
</record>

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