Antibody Response and Disease Severity in Healthcare Worker MERS Survivors
Identifieur interne : 000063 ( Pmc/Corpus ); précédent : 000062; suivant : 000064Antibody Response and Disease Severity in Healthcare Worker MERS Survivors
Auteurs : Abeer N. Alshukairi ; Imran Khalid ; Waleed A. Ahmed ; Ashraf M. Dada ; Daniyah T. Bayumi ; Laut S. Malic ; Sahar Althawadi ; Kim Ignacio ; Hanadi S. Alsalmi ; Hail M. Al-Abdely ; Ghassan Y. Wali ; Ismael A. Qushmaq ; Basem M. Alraddadi ; Stanley PerlmanSource :
- Emerging Infectious Diseases [ 1080-6040 ] ; 2016.
Abstract
We studied antibody response in 9 healthcare workers in Jeddah, Saudi Arabia, who survived Middle East respiratory syndrome, by using serial ELISA and indirect immunofluorescence assay testing. Among patients who had experienced severe pneumonia, antibody was detected for
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DOI: 10.3201/eid2206.160010
PubMed: 27192543
PubMed Central: 4880093
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Antibody Response and Disease Severity in Healthcare Worker MERS Survivors</title><author><name sortKey="Alshukairi, Abeer N" sort="Alshukairi, Abeer N" uniqKey="Alshukairi A" first="Abeer N." last="Alshukairi">Abeer N. Alshukairi</name></author><author><name sortKey="Khalid, Imran" sort="Khalid, Imran" uniqKey="Khalid I" first="Imran" last="Khalid">Imran Khalid</name></author><author><name sortKey="Ahmed, Waleed A" sort="Ahmed, Waleed A" uniqKey="Ahmed W" first="Waleed A." last="Ahmed">Waleed A. Ahmed</name></author><author><name sortKey="Dada, Ashraf M" sort="Dada, Ashraf M" uniqKey="Dada A" first="Ashraf M." last="Dada">Ashraf M. Dada</name></author><author><name sortKey="Bayumi, Daniyah T" sort="Bayumi, Daniyah T" uniqKey="Bayumi D" first="Daniyah T." last="Bayumi">Daniyah T. Bayumi</name></author><author><name sortKey="Malic, Laut S" sort="Malic, Laut S" uniqKey="Malic L" first="Laut S." last="Malic">Laut S. Malic</name></author><author><name sortKey="Althawadi, Sahar" sort="Althawadi, Sahar" uniqKey="Althawadi S" first="Sahar" last="Althawadi">Sahar Althawadi</name></author><author><name sortKey="Ignacio, Kim" sort="Ignacio, Kim" uniqKey="Ignacio K" first="Kim" last="Ignacio">Kim Ignacio</name></author><author><name sortKey="Alsalmi, Hanadi S" sort="Alsalmi, Hanadi S" uniqKey="Alsalmi H" first="Hanadi S." last="Alsalmi">Hanadi S. Alsalmi</name></author><author><name sortKey="Al Abdely, Hail M" sort="Al Abdely, Hail M" uniqKey="Al Abdely H" first="Hail M." last="Al-Abdely">Hail M. Al-Abdely</name></author><author><name sortKey="Wali, Ghassan Y" sort="Wali, Ghassan Y" uniqKey="Wali G" first="Ghassan Y." last="Wali">Ghassan Y. Wali</name></author><author><name sortKey="Qushmaq, Ismael A" sort="Qushmaq, Ismael A" uniqKey="Qushmaq I" first="Ismael A." last="Qushmaq">Ismael A. Qushmaq</name></author><author><name sortKey="Alraddadi, Basem M" sort="Alraddadi, Basem M" uniqKey="Alraddadi B" first="Basem M." last="Alraddadi">Basem M. Alraddadi</name></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">27192543</idno><idno type="pmc">4880093</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880093</idno><idno type="RBID">PMC:4880093</idno><idno type="doi">10.3201/eid2206.160010</idno><date when="2016">2016</date><idno type="wicri:Area/Pmc/Corpus">000063</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000063</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Antibody Response and Disease Severity in Healthcare Worker MERS Survivors</title><author><name sortKey="Alshukairi, Abeer N" sort="Alshukairi, Abeer N" uniqKey="Alshukairi A" first="Abeer N." last="Alshukairi">Abeer N. Alshukairi</name></author><author><name sortKey="Khalid, Imran" sort="Khalid, Imran" uniqKey="Khalid I" first="Imran" last="Khalid">Imran Khalid</name></author><author><name sortKey="Ahmed, Waleed A" sort="Ahmed, Waleed A" uniqKey="Ahmed W" first="Waleed A." last="Ahmed">Waleed A. Ahmed</name></author><author><name sortKey="Dada, Ashraf M" sort="Dada, Ashraf M" uniqKey="Dada A" first="Ashraf M." last="Dada">Ashraf M. Dada</name></author><author><name sortKey="Bayumi, Daniyah T" sort="Bayumi, Daniyah T" uniqKey="Bayumi D" first="Daniyah T." last="Bayumi">Daniyah T. Bayumi</name></author><author><name sortKey="Malic, Laut S" sort="Malic, Laut S" uniqKey="Malic L" first="Laut S." last="Malic">Laut S. Malic</name></author><author><name sortKey="Althawadi, Sahar" sort="Althawadi, Sahar" uniqKey="Althawadi S" first="Sahar" last="Althawadi">Sahar Althawadi</name></author><author><name sortKey="Ignacio, Kim" sort="Ignacio, Kim" uniqKey="Ignacio K" first="Kim" last="Ignacio">Kim Ignacio</name></author><author><name sortKey="Alsalmi, Hanadi S" sort="Alsalmi, Hanadi S" uniqKey="Alsalmi H" first="Hanadi S." last="Alsalmi">Hanadi S. Alsalmi</name></author><author><name sortKey="Al Abdely, Hail M" sort="Al Abdely, Hail M" uniqKey="Al Abdely H" first="Hail M." last="Al-Abdely">Hail M. Al-Abdely</name></author><author><name sortKey="Wali, Ghassan Y" sort="Wali, Ghassan Y" uniqKey="Wali G" first="Ghassan Y." last="Wali">Ghassan Y. Wali</name></author><author><name sortKey="Qushmaq, Ismael A" sort="Qushmaq, Ismael A" uniqKey="Qushmaq I" first="Ismael A." last="Qushmaq">Ismael A. Qushmaq</name></author><author><name sortKey="Alraddadi, Basem M" sort="Alraddadi, Basem M" uniqKey="Alraddadi B" first="Basem M." last="Alraddadi">Basem M. Alraddadi</name></author><author><name sortKey="Perlman, Stanley" sort="Perlman, Stanley" uniqKey="Perlman S" first="Stanley" last="Perlman">Stanley Perlman</name></author></analytic><series><title level="j">Emerging Infectious Diseases</title><idno type="ISSN">1080-6040</idno><idno type="eISSN">1080-6059</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>We studied antibody response in 9 healthcare workers in Jeddah, Saudi Arabia, who survived Middle East respiratory syndrome, by using serial ELISA and indirect immunofluorescence assay testing. Among patients who had experienced severe pneumonia, antibody was detected for <underline>></underline>18 months after infection. Antibody longevity was more variable in patients who had experienced milder disease.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct></biblStruct></listBibl></div1></back></TEI><pmc article-type="brief-report"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Emerg Infect Dis</journal-id><journal-id journal-id-type="iso-abbrev">Emerging Infect. Dis</journal-id><journal-id journal-id-type="publisher-id">EID</journal-id><journal-title-group><journal-title>Emerging Infectious Diseases</journal-title></journal-title-group><issn pub-type="ppub">1080-6040</issn><issn pub-type="epub">1080-6059</issn><publisher><publisher-name>Centers for Disease Control and Prevention</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">27192543</article-id><article-id pub-id-type="pmc">4880093</article-id><article-id pub-id-type="publisher-id">16-0010</article-id><article-id pub-id-type="doi">10.3201/eid2206.160010</article-id><article-categories><subj-group subj-group-type="heading"><subject>Dispatch</subject></subj-group><subj-group subj-group-type="article-type"><subject>Dispatch</subject></subj-group><subj-group subj-group-type="TOC-title"><subject>Antibody Response and Disease Severity in Healthcare Worker MERS Survivors</subject></subj-group></article-categories><title-group><article-title>Antibody Response and Disease Severity in Healthcare Worker MERS Survivors</article-title><alt-title alt-title-type="running-head">Antibody Response in MERS Survivors</alt-title></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name><surname>Alshukairi</surname><given-names>Abeer N.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Khalid</surname><given-names>Imran</given-names></name></contrib><contrib contrib-type="author"><name><surname>Ahmed</surname><given-names>Waleed A.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Dada</surname><given-names>Ashraf M.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Bayumi</surname><given-names>Daniyah T.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Malic</surname><given-names>Laut S.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Althawadi</surname><given-names>Sahar</given-names></name></contrib><contrib contrib-type="author"><name><surname>Ignacio</surname><given-names>Kim</given-names></name></contrib><contrib contrib-type="author"><name><surname>Alsalmi</surname><given-names>Hanadi S.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Al-Abdely</surname><given-names>Hail M.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Wali</surname><given-names>Ghassan Y.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Qushmaq</surname><given-names>Ismael A.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Alraddadi</surname><given-names>Basem M.</given-names></name></contrib><contrib contrib-type="author"><name><surname>Perlman</surname><given-names>Stanley</given-names></name></contrib><aff id="aff1">King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia (A.N. Alshukairi, I. Khalid, W.A. Ahmed, A.M. Dada, D.T. Bayumi, L.S. Malic, H.S. Alsalmi, G.Y. Wali, I.A. Qushmaq, B.M. Alraddadi);</aff><aff id="aff2">King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia (S. Althawadi, K. Ignacio);</aff><aff id="aff3">General Directorate of Infection Prevention and Control, Ministry of Health, Riyadh (H.M. Al-Abdely);</aff><aff id="aff4">University of Iowa Department of Microbiology, Iowa City, Iowa, USA (S. Perlman)</aff></contrib-group><author-notes><corresp id="cor1">Address for correspondence: Abeer N. Alshukairi, King Faisal Specialist Hospital and Research Center, Department of Medicine, PO Box 6653, Jeddah 21452, Saudi Arabia; email: <email xlink:href="abeer_sh@doctor.com">abeer_sh@doctor.com</email></corresp></author-notes><pub-date pub-type="ppub"><month>6</month><year>2016</year></pub-date><volume>22</volume><issue>6</issue><fpage>1113</fpage><lpage>1115</lpage><abstract><p>We studied antibody response in 9 healthcare workers in Jeddah, Saudi Arabia, who survived Middle East respiratory syndrome, by using serial ELISA and indirect immunofluorescence assay testing. Among patients who had experienced severe pneumonia, antibody was detected for <underline>></underline>18 months after infection. Antibody longevity was more variable in patients who had experienced milder disease.</p></abstract><kwd-group kwd-group-type="author"><title>Keywords: </title><kwd>antibody</kwd><kwd>Middle East respiratory syndrome coronavirus</kwd><kwd>MERS-CoV</kwd><kwd>ELISA</kwd><kwd>indirect immunofluorescence assay</kwd><kwd>IFA</kwd><kwd>healthcare workers</kwd><kwd>immune response</kwd><kwd>viruses</kwd><kwd>Jeddah</kwd><kwd>Saudi Arabia</kwd></kwd-group></article-meta></front><body><p>A study evaluating the immune response in patients infected with severe acute respiratory syndrome coronavirus (SARS-CoV) showed antivirus antibodies in survivors can be detected by ELISA and immunofluorescence assay (IFA) for up to 24 months after infection (<xref rid="R1" ref-type="bibr"><italic>1</italic></xref>). Another study revealed that SARS-CoV antibodies were not detectable at 6 years after infection (<xref rid="R2" ref-type="bibr"><italic>2</italic></xref>). Antibody response to Middle East respiratory syndrome coronavirus (MERS-CoV) typically is detected in the second and third week after the onset of the infection (<xref rid="R3" ref-type="bibr"><italic>3</italic></xref>–<xref rid="R5" ref-type="bibr"><italic>5</italic></xref>), but little is known about the longevity of the response or whether the decrease in antibody response over time correlates with the severity of the initial infection. We conducted a longitudinal study of antibody response among a cohort of MERS survivors who had been treated at King Faisal Specialist Hospital and Research Center in Jeddah, Saudi Arabia (KFSHRC-J).</p><sec><title>The Study</title><p>Our research proposal was approved by the KFSHRC-J institutional review board. Written informed consent was obtained from all study participants. During the Jeddah MERS outbreak in 2014, we tested specimens from 1,412 patients with suspected MERS-CoV infection by using a real-time reverse transcription PCR (rRT-PCR) assay. We identified 40 confirmed cases on the basis of rRT-PCR–positive specimens obtained by nasopharyngeal swab or bronchoalveolar lavage, as described previously (<xref rid="R6" ref-type="bibr"><italic>6</italic></xref>; <xref ref-type="local-data" rid="SD1">Technical Appendix</xref>). For each patient, <underline>></underline>2 specimens were analyzed and rRT-PCR was conducted twice. Eighteen of 40 cases were in healthcare workers (HCWs); 12 of these 18 HCWs were symptomatic. The 6 asymptomatic HCWs were identified through contact tracing during active hospital surveillance for MERS cases. The patient cohort for this study consisted of 9 HCWs who were MERS-CoV–positive on the basis of rRT-PCR results and who agreed to provide blood samples for serial serologic testing for MERS-CoV by ELISA and IFA. </p><p>Patients’ medical records were reviewed for information on demographic characteristics, comorbidities, clinical presentation, intensive care unit admission, and outcome. Patients were classified into 4 categories according to their clinical presentation: asymptomatic, upper respiratory tract infection, pneumonia, or severe pneumonia. Patients with severe pneumonia were those who required intubation and ventilatory support and were treated in an intensive care unit. Serial ELISA and IFA testing was performed at 3, 10 and 18 months after illness onset (<xref ref-type="local-data" rid="SD1">Technical Appendix</xref>). Specimens were considered to represent previous infection only when ELISA and IFA test results both were positive. Microneutralization testing was not available in the KFSHRC-J laboratory.</p><p>Disease onset corresponded to the date of the first MERS-CoV–positive rRT-PCR result. Data were available for analysis from 9 patients who were MERS-CoV–positive and had serial MERS-CoV serologic testing at 3 and 10 months after illness onset. Patients with severe pneumonia who were MERS-CoV-antibody–positive at 10 months had follow-up testing at 18 months. Serum samples could not be obtained from patient 3, who was also MERS-CoV-antibody–positive at 10 months. All patients were initially healthy without underlying conditions except patient 2 (<xref ref-type="table" rid="T1">Table</xref>), who had hypothyroidism. Four of the 9 patients were women; 2 of them, patients 2 and 8, were 32 weeks and 20 weeks’ pregnant, respectively, when they had MERS-CoV infection. Average patient age was 38 years (range 27–54 years). </p><table-wrap id="T1" position="float"><label>Table</label><caption><title>Antibody response in 9 confirmed survivors of MERS-CoV infection, by selected demographic and clinical characteristics, King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia, 2014*</title></caption><table frame="hsides" rules="groups"><col width="35" span="1"></col><col width="31" span="1"></col><col width="74" span="1"></col><col width="35" span="1"></col><col width="35" span="1"></col><col width="9" span="1"></col><col width="47" span="1"></col><col width="33" span="1"></col><col width="9" span="1"></col><col width="47" span="1"></col><col width="33" span="1"></col><col width="9" span="1"></col><col width="41" span="1"></col><col width="35" span="1"></col><thead><tr><th rowspan="3" valign="bottom" align="left" scope="col" colspan="1">Patient no.<hr></hr></th><th rowspan="3" valign="bottom" align="center" scope="col" colspan="1">Age, y/sex<hr></hr></th><th rowspan="3" valign="bottom" align="center" scope="col" colspan="1">Clinical presentation<hr></hr></th><th valign="bottom" colspan="11" align="center" scope="colgroup" rowspan="1">Test results<hr></hr></th></tr><tr><th valign="bottom" colspan="2" align="center" scope="colgroup" rowspan="1">PCR, C<sub>t</sub><hr></hr></th><th rowspan="2" valign="bottom" align="left" scope="col" colspan="1"><hr></hr></th><th valign="bottom" colspan="2" align="center" scope="colgroup" rowspan="1">Serology at 3 mo<hr></hr></th><th rowspan="2" valign="bottom" align="left" scope="col" colspan="1"><hr></hr></th><th valign="bottom" colspan="2" align="center" scope="colgroup" rowspan="1">Serology at 10 mo<hr></hr></th><th rowspan="2" valign="bottom" align="left" scope="col" colspan="1"><hr></hr></th><th valign="bottom" colspan="2" align="center" scope="colgroup" rowspan="1">Serology at 18 mo<hr></hr></th></tr><tr><th valign="bottom" colspan="1" align="center" scope="colgroup" rowspan="1">NPS<hr></hr></th><th valign="bottom" align="center" scope="col" rowspan="1" colspan="1">BAL<hr></hr></th><th valign="bottom" colspan="1" align="center" scope="colgroup" rowspan="1">ELlSA†<hr></hr></th><th valign="bottom" align="center" scope="col" rowspan="1" colspan="1">IFA‡<hr></hr></th><th valign="bottom" colspan="1" align="center" scope="colgroup" rowspan="1">ELISA†<hr></hr></th><th valign="bottom" align="center" scope="col" rowspan="1" colspan="1">IFA‡<hr></hr></th><th valign="bottom" colspan="1" align="center" scope="colgroup" rowspan="1">ELISA†<hr></hr></th><th valign="bottom" align="center" scope="col" rowspan="1" colspan="1">IFA‡<hr></hr></th></tr><tr><th valign="top" align="left" scope="col" rowspan="1" colspan="1">1</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">49/M</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">Severe pneumonia</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">28</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">26</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+ (3.17)</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+ (2.99)</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+ (3.3)</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+</th></tr><tr><th valign="top" align="left" scope="col" rowspan="1" colspan="1">2</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">33/F</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">Severe pneumonia</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">31</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">26</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+ (2.7)</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+ (2.09)</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+ (2.9)</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+</th></tr><tr><th valign="top" align="left" scope="col" rowspan="1" colspan="1">3</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">54/F</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">Pneumonia</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">34</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+ (2.91)</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+ (1.9)</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th></tr><tr><th valign="top" align="left" scope="col" rowspan="1" colspan="1">4</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">40/M</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">Pneumonia</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">32</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+ (1.29)</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">– (0.65)</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">–</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th></tr><tr><th valign="top" align="left" scope="col" rowspan="1" colspan="1">5</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">37/M</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">Pneumonia</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">35</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+ (3.2)</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">+ (1.2)</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">–</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th></tr><tr><th valign="top" align="left" scope="col" rowspan="1" colspan="1">6</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">36/M</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">URTI</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">32</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">– (0.07)</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">–</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">– (0.07)</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">–</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th></tr><tr><th valign="top" align="left" scope="col" rowspan="1" colspan="1">7</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">27/F</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">Asymptomatic</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">33</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">– (0.046)</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">–</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">– (0.04)</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">–</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th></tr><tr><th valign="top" align="left" scope="col" rowspan="1" colspan="1">8</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">28/F</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">Asymptomatic</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">32</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">– (0.12)</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">–</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">– (0.06)</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">–</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th></tr><tr><th valign="top" align="left" scope="col" rowspan="1" colspan="1">9</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">35/M</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">Asymptomatic</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">33</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">– (0.07)</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">–</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">– (0.04)</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">–</th><th valign="top" align="left" scope="col" rowspan="1" colspan="1"></th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th><th valign="top" align="center" scope="col" rowspan="1" colspan="1">ND</th></tr></thead><tbody><tr><td rowspan="1" colspan="1"></td></tr></tbody></table><table-wrap-foot><p>*+, positive; –, negative; BAL, broncholaveolar lavage; Ct, cycle threshold; IFA, indirect-immunofluorescence assay; MERS-CoV, Middle East respiratory syndrome coronavirus; ND, not done; NPS, nasopharyngeal swab; URTI, upper respiratory tract infection.
†ELISA for MERS-CoV S gene antibody; positive defined as a value >1.1, negative as <0.8, and borderline as between 0.8 and 1.1.
‡IFA for MERS-CoV IgG; endpoint titers not done.</p></table-wrap-foot></table-wrap><p>Of the 9 patients, 2 had severe pneumonia, 3 had milder pneumonia not requiring intensive care, 1 had upper respiratory tract disease, and 3 remained asymptomatic. All patients recovered without sequelae. The 2 patients with severe pneumonia had the highest antibody titers detected among all patients and remained MERS-CoV-antibody–positive when tested at 18 months after illness onset. They also had prolonged viral shedding documented by persistent positive rRT-PCR results for 13 days (patient 1) and 12 days (patient 2); rRT-PCR analyses were negative after 2–5 days for patients 4–9. rRT-PCR was only repeated at day 13 for patient 3, and the result was negative. Three patients with pneumonia were MERS-CoV-antibody–positive at 3 months, but antibody was detected in only 1 of the 3 at 10 months (<xref ref-type="table" rid="T1">Table</xref>). All patients who had an upper respiratory tract function or remained asymptomatic had no detectable antibody response on the basis of ELISA and IFA results.</p></sec><sec sec-type="conclusions"><title>Conclusions</title><p>Our results indicate that the longevity of the MERS-CoV antibody response correlated with disease severity. Accordingly, 2 patients with severe MERS-associated pneumonia had a persistent antibody response detected for <underline>></underline>18 months after infection, whereas patients with disease confined to the upper respiratory tract or who had no clinical signs had no detectable MERS-CoV antibody response. Two previous studies have described longitudinal analyses of MERS-CoV surface glycoprotein–specific antibody responses in recovered patients. In the first study, which described a MERS outbreak in Jordan (<xref rid="R7" ref-type="bibr"><italic>7</italic></xref>), MERS-CoV antibodies, including neutralizing antibodies, were still detectable in 7 patients with pneumonia 13 months after infection; most of these patients had severe pneumonia. In the second study, Drosten et al. (<xref rid="R8" ref-type="bibr"><italic>8</italic></xref>) demonstrated that MERS-CoV neutralizing antibodies were produced at low levels after mild or subclinical infection and were potentially short-lived.</p><p>The results of our study have implications for understanding the pathogenesis and the treatment of MERS. First, patients with mild or subclinical infections who had no detectable antibody response might be at risk for recurrent infection and would also not be detected in population-based studies, resulting in falsely low prevalence rates. Previous studies suggest that neutralizing antibodies were not sufficient to clear MERS-CoV, because neutralizing antibodies were detected in up to 50% of fatal MERS cases and antibody levels did not correlate well with virus load in the lungs (<xref rid="R3" ref-type="bibr"><italic>3</italic></xref>). T-cell responses are critical for protection from subsequent challenge in animals experimentally infected with SARS-CoV (<xref rid="R9" ref-type="bibr"><italic>9</italic></xref>). Although T cells have persisted up to 6 years in SARS survivors (<xref rid="R2" ref-type="bibr"><italic>2</italic></xref>), whether these patients would have been protected if infected a second time with SARS-CoV is unknown. Additional studies will be required to assess the relative importance of T- and B-cell responses in MERS survivors. Second, we speculate that patients with low-level virus replication could provide a reservoir for infection of highly susceptible humans (i.e., those with underlying conditions). Such patients would be difficult to detect because they are only transiently positive for MERS-CoV antibody or might never mount an antibody response to MERS-CoV. Third, patients who recovered from severe pneumonia associated with MERS probably would be good candidates for providing MERS-CoV–specific convalescent-phase serum samples for use in treatment trials.</p><p>Our study is limited by the small number of patient numbers and the lack of neutralizing antibody testing. ELISA is highly sensitive but might cross-react with seasonal human coronavirus antibodies (<xref rid="R10" ref-type="bibr"><italic>10</italic></xref>); it is useful as a screening test because it is 10-fold more sensitive than IFA. An IFA is required for confirmation (<xref rid="R11" ref-type="bibr"><italic>11</italic></xref>), and use of a spike protein–specific IFA greatly diminishes the likelihood of cross-reactivity. Neutralization assays are considered definitive and must be performed whenever the results of ELISA and IFA are not conclusive (<xref rid="R12" ref-type="bibr"><italic>12</italic></xref>). In the 9 patients reported here, ELISA and IFA results were consistent and conclusive. A limitation of this study is that serologic testing from single patients was not performed on the same day; therefore, only qualitative but not quantitative conclusions about changes with time after illness onset can be made. </p><p>In conclusion, our results indicate that MERS-CoV antibody persistence depends on disease severity. Further studies are required to determine the role of the virus-specific T-cell response in MERS patients and determine whether patients with mild infections are at risk for reinfection and would therefore benefit from vaccination. Our data also show that potential donors of MERS-CoV convalescent-phase serum samples are limited to patients who recover from severe pneumonia.</p></sec><sec sec-type="supplementary-material"><title></title><supplementary-material content-type="local-data" id="SD1"><caption><title>Technical Appendix</title><p>Methods and materials used for a longitudinal study of antivirus antibody response after MERS-CoV infection, conducted at King Faisal Specialist Hospital and Research Center, Jeddah, Saudi Arabia, 2014.</p></caption><media mimetype="application" mime-subtype="pdf" xlink:href="16-0010-Techapp-s1.pdf" xlink:type="simple" id="d36e617" position="anchor"></media></supplementary-material></sec></body><back><fn-group><fn fn-type="citation"><p><italic>Suggested citation for this article</italic>: Alshukairi AN, Khalid I, Ahmed WA, Dada AM, Bayumi DT, Malic LS, et al. Antibody response and disease severity in healthcare worker MERS survivors. Emerg Infect Dis. 2016 June [<italic>date cited</italic>]. <ext-link ext-link-type="uri" xlink:href="http://dx.doi.org/10.3201/eid2206.160010">http://dx.doi.org/10.3201/eid2206.160010</ext-link></p></fn></fn-group><ack><title>Acknowledgments</title><p>We thank Mohamma Rasmi Gabajah for help in obtaining blood samples from HCWs.</p><p>This work was supported by the Pathology Department at KFSHRC-J. S.P. was supported by a grant from the US National Institutes of Health (grant no. PO1 AI060699).</p></ack><bio id="d36e637"><p>Dr. Alshukairi is an infectious diseases consultant at KFSHRC-J. 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