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order-lg-2 syndicate" aria-label="Main Content Area"> <h5 class="header"> Volume 13, Number 10—October 2007 </h5> <h5 class="header"><em>Dispatch</em></h5> <h3 class="header article-title"> Duration of Antibody Responses after Severe Acute Respiratory Syndrome </h3>  <div class="right-col-info"> <div class="card mb-2"> <div class="card-header"> On This Page </div> <div class="card-body"> <a href="#" onclick="$('#thestudy').scrollView();" aria-label="scroll to section">The Study</a> <hr /> <a href="#" onclick="$('#conclusions').scrollView();" aria-label="scroll to section">Conclusions</a> <hr /> <a href="#" onclick="showPopUp(); $('#showLink').scrollView();">Cite This Article</a> </div> </div> <div class="card mb-2"> <div class="card-header"> Figures </div> <div class="card-body"> <a href="/eid/article/13/10/07-0576-f1">Figure 1</a> <hr /> <a href="/eid/article/13/10/07-0576-f2">Figure 2</a> </div> </div> <div class="card mb-2"> <div class="card-header"> Tables </div> <div 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</div> </div> <div class="card mb-2"> <div class="card-body" style="padding:6px;"> <div style="font-size:1.8em;display:inline-block;"> <b>310</b> </div> <a href="https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=35548934673&origin=inward" class="external-link">citations</a> of this article <br /> EID Journal Metrics on <a href="https://www.scopus.com/sourceid/20228?origin=recordpage" class="external-link">Scopus</a> </div> </div> </div>  <div id="authors" class="strong" style="visibility: hidden;"> Li-Ping Wu*, Nai-Chang Wang*, Yi-Hua Chang*, Xiang-Yi Tian*, Dan-Yu Na*, Li-Yuan Zhang*, Lei Zheng*, Tao Lan†, Lin-Fa Wang‡, and Guo-Dong Liang§<a href="#comment" class="corresponding-author-image"><img src="/eid/content/images/icon/email.gif" alt="Comments to Author" border="0" height="9" width="12"></a>  </div> <div id="author-affiliations"> <span class="affiliation-label">Author affiliations: </span> <span class="affiliation">*Shanxi Provincial Center for Disease Control and Prevention, Taiyuan, People’s Republic of China</span>; <span class="affiliation">†Shanxi Provincial Peoples’ Hospital, Taiyuan, People’s Republic of China</span>; <span class="affiliation">‡CSIRO Australian Animal Health Laboratory and Australian Biosecurity Center for Emerging Infectious Diseases, Geelong, Victoria, Australia</span>; <span class="affiliation">§State Key Laboratory for Infectious Disease Control and Prevention, Beijing, People’s Republic of China</span>; </div> <p><a id="showLink" onclick="showPopUp()" href="#;" title="Show Article Citations">Cite This Article</a></p>  <button id="btnOpenCitationModal" type="button" data-toggle="modal" data-target="#citationModalDialog" style="display:none;"> Open modal </button> <div id="abstract" class="card"> <div class="card-body bg-tertiary"> <h3>Abstract</h3> <p>Among 176 patients who had had severe acute respiratory syndrome (SARS), SARS-specific antibodies were maintained for an average of 2 years, and significant reduction of immunoglobulin G–positive percentage and titers occurred in the third year. Thus, SARS patients might be susceptible to reinfection <span class="text-underline">></span>3 years after initial exposure.</p> </div> </div> <div id="mainbody"> <p>Severe acute respiratory syndrome (SARS) represents the first pandemic transmissible disease to emerge in this century. It was caused by a previously unknown coronavirus, the SARS-associated coronavirus (SARS-CoV) (<a href="#r1" title="1"><em>1</em></a>). SARS-CoV spreads from animals to humans by a rapid adaptation and evolution process (<a href="#r2" title="2"><em>2</em></a>,<a href="#r3" title="3"><em>3</em></a>). A large number of closely related viruses are present in wildlife reservoir populations (<a href="#r4" title="4"><em>4</em></a>–<a href="#r6" title="6"><em>6</em></a>). Therefore, due to cross-species transmission of the same or a similar coronavirus, SARS could recur. Immune protection against infection with other human coronaviruses, such as OC43 and 229E, is short-lived (<a href="#r7" title="7"><em>7</em></a>). To assess SARS patients’ risk for future reinfection, we conducted a longitudinal study of immunity in convalescent patients.</p> <div class="xml-section"> <div><a class="onThisPageAnchor" id="thestudy" name="thestudy" title="The Study"></a><h3>The Study</h3></div> <p>Shanxi Province in China was 1 of the SARS epicenters during the 2002–03 outbreaks. For our study, serum samples were taken from patients in 7 designated SARS hospitals in the province during March–August 2003. Follow-up serum samples were taken at 6 months, 1, 2, and 3 years after the onset of symptoms. A total of 176 cases that met the World Health Organization (WHO) SARS case definition (<a href="#r8" title="8"><em>8</em></a>) and had known transmission history were included in this study. The study was conducted as part of a national SARS control and prevention program; use of serum from human participants was approved by the Committee for SARS Control and Prevention, Department of Science and Technology, the People’s Republic of China.</p> <p>Titers of serum antibodies to SARS-CoV were determined by using a commercially available ELISA kit (BJI-GBI Biotechnology, Beijing, China). The ELISA was based on an inactivated preparation of whole-virus lysate. The kit was the first commercial kit approved by the Chinese Food and Drug Administration for specific detection of SARS-CoV antibodies and has been widely used in several studies (<a href="#r9" title="9"><em>9</em></a>–<a href="#r11" title="11"><em>11</em></a>). Manufacturer’s instructions were followed without modification. Briefly, for every ELISA plate, 1 blank, 1 positive, and 2 negative controls were included. For detection of immunoglobulin G (IgG), a 1:10 dilution of testing serum (100 μL) was added to antigen-coated wells, and the plate was incubated at 37<sup>o</sup>C for 30 min. Horseradish peroxide (HRP)–conjugated antihuman IgG (100 μL) was then added for detection of bound antibodies. For detection of IgM, the incubation of primary antibodies was extended to 60 min, followed by detection with HRP-conjugated antihuman IgM. Optical density (OD) readings were deemed valid only when the negative control OD was <span class="text-underline"><</span>0.10 and the positive control was <span class="text-underline">></span>0.50 on the same ELISA plate. The cutoff for IgG and IgM determination was defined as 0.13 and 0.11, respectively, plus OD of the negative control. When the OD of the negative control was <0.05, 0.05 was used for the calculation. In this study, the OD readings of negative controls from different testing were consistently <0.05, so the cutoff ODs for IgG and IgM were 0.18 and 0.16, respectively. Serum samples that had an OD greater than or equal to the cutoff value were considered positive. Weak positive samples (i.e., OD<2× cutoff value) were retested in duplicate on the same day; only reproducible positive results were included in the final analysis. All data were processed by using Excel version 7.0 (Microsoft Corp., Redmond, WA, USA) and SPSS software version 10 for Windows (SPSS Inc., Chicago, IL, USA).</p> <a name="tnF1"></a><div id="attachment-F1" class="card attachment-card ml-1 mb-3"><p class="label">Figure 1</p><div class="caption"><img src="/eid/images/07-0576-F1-tn.jpg" alt="Thumbnail of Change of immunoglobulin G (IgG) patterns among 176 convalescent severe acute respiratory syndrome patients with known transmission history. See the Table for number of samples used for the calculation at each time point. OD, optical density." width="150" height="69"><p><a href="/eid/content/13/10/1562-f1.htm" title="Figure 1">Figure 1</a>. Change of immunoglobulin G (IgG) patterns among 176 convalescent severe acute respiratory syndrome patients with known transmission history. See the Table for number of samples used for the calculation at each...</p></div></div><p>Among the cohort, 163 (92.61%) of 176 (χ<sup>2</sup> = 200.11, p = 0.000002) were IgG positive, which indicated that most patients who met the WHO case definition were indeed infected with SARS-CoV. As shown in the Table, at ≈7 days after the onset of symptoms, the percentage who were IgG positive was ≈11.80%. This percentage continued to increase, reached 100% at 90 days, and remained largely unchanged up to 200 days. Furthermore, after 1 and 2 years 93.88% and 89.58% of patients, respectively, were IgG positive, which suggests that the immune responses were maintained in <span class="text-underline">></span>90% of patients for 2 years. However, 3 years later, ≈50% of the convalescent population had no SARS-CoV–specific IgG. The OD changes correlated with the changes to the IgG-positive percentage, although the rate of change varied. Both the OD readings (0.93) and positive percentages peaked at 90–120 days; however, the rate of reduction of the average OD readings was much faster, dropping by 22% (0.73) and 40% (0.54) at 1 and 2 years, respectively, after symptom onset (<a href="#tnF1" title="Figure 1">Figure 1</a>).</p> <span></span> <p>A similar observation was obtained for IgM trends in this same cohort. The percentage of patients who were IgM positive within the first 7 days was 21.4% and peaked at 76.2% after 21–30 days (<a href="/eid/content/13/10/1562-t1.htm" title="Table">Table</a>). The patterns of IgM-positive percentage and average OD readings were similar; both peaked at 21–30 days. After 60 days, the average OD readings dropped to 0.167, close to the cutoff value of 0.160.</p> <div></div> <a name="tnF2"></a><div id="attachment-F2" class="card attachment-card ml-1 mb-3"><p class="label">Figure 2</p><div class="caption"><img src="/eid/images/07-0576-F2-tn.jpg" alt="Thumbnail of Change of immunoglobulin G (IgG) patterns among 18 convalescent severe acute respiratory syndrome patients with a complete collection of sequential serum samples at the time points shown. The 18 patients were selected from the cohort of 176 patients for whom transmission history was known. OD, optical density." width="150" height="71"><p><a href="/eid/content/13/10/1562-f2.htm" title="Figure 2">Figure 2</a>. Change of immunoglobulin G (IgG) patterns among 18 convalescent severe acute respiratory syndrome patients with a complete collection of sequential serum samples at the time points shown. The 18 patients were...</p></div></div><p>Among the cohort of patients with known transmission histories, we were able to obtain a complete collection of serum samples from 18 patients at 6 months, 1, 2, and 3 years. The IgG levels of these 18 patients were analyzed separately to obtain an IgG trend that more accurately represented convalescent SARS patients (<a href="#tnF2" title="Figure 2">Figure 2</a>). All 18 patients had positive IgG at 6 months and at 1 year (i.e., 100% positive); only 1 patient became IgG negative at 2 years. However, at 3 years, the positive percentage dropped to 55.56%. The reduction of OD values mimicked that of the positive percentage, again at a faster rate. The average OD readings dropped from 0.94 at 6 months to 0.64 at 1 year, which represents a reduction of 33.33%. The OD further dropped to 0.52 (45.83% reduction) by 2 years and to 0.25 by 3 years.</p> <span></span> </div> <div class="xml-section"> <div><a class="onThisPageAnchor" id="conclusions" name="conclusions" title="Conclusions"></a><h3>Conclusions</h3></div> <p>To our knowledge, the 3-year follow-up conducted in this study is the longest longitudinal study ever reported. With a large number of patients who had confirmed transmission history (176) and a complete dataset for 18, the level of confidence is high that the results obtained in this study are representative for convalescent SARS patients. Similar results have been reported from longitudinal studies of SARS patients with smaller cohort size (18–98 patients) and shorter follow-up period (240 days to 2 years) (<a href="#r9" title="9"><em>9</em></a>–<a href="#r14" title="14"><em>14</em></a>). The general trend of IgM peaking at ≈1 month after symptom onset and IgG peaking at 2–4 months was consistent among different studies.</p> <p>Our results provide strong evidence that SARS-CoV antibodies are reduced <span class="text-underline">></span>3 years after the symptom onset. Because antibodies play an important role in protective immunity against SARS-CoV (<a href="#r15" title="15"><em>15</em></a>), the findings from this study will have important implications with regard to assessing risk for reinfection among previously exposed populations (e.g., hospital staff) and evaluating the duration of antibody-mediated immunity that any candidate vaccine could provide.</p> </div><div class="blockquote-indent"> <p>Dr Wu is a professor at the Shanxi Provincial Center for Disease Control and Prevention, Taiyuan, China, who specializes in medical microbiology. Her current research interests include the detection and diagnosis of emerging infectious agents.</p> </div> <p class="topLinkStyle"> <a href="javascript:void(0)" onclick="ScrollToTop()">Top</a> </p> </div> <div class="clear"></div> <h3>Acknowledgments</h3> <div class="blockquote-indent"> <title></title> <p>We thank Zhi-Qiang Mei, Xi-Fang Zhao, Xiao-Wei Deng, and Jian-Min Ji for help with sample processing.</p> <p>This work was supported by grants from National Science and Technology Department of China (no. 2003AA 208405) to G.-D.L and the Science and Technology of the Shanxi Province (no. 032001) to L.-P.W.</p> </div> <p class="topLinkStyle"> <a href="javascript:void(0)" onclick="ScrollToTop()">Top</a> </p> <h3>References</h3> <div id="articlereferences" class="references"> <ol><li id="r1"><div class="journal" class="citation"><span class="xml-string-name"><span class="xml-surname">Peiris </span> <span class="xml-given-names">JSM</span></span>, <span class="xml-string-name"><span 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class="attachments ft-14"> <li> <a href="/eid/article/13/10/07-0576-f1"> <strong>Figure 1</strong>.  Change of immunoglobulin G (IgG) patterns among 176 convalescent severe acute respiratory syndrome patients with known transmission history. See the Table for number of samples used for the calculation at... </a> </li> <li> <a href="/eid/article/13/10/07-0576-f2"> <strong>Figure 2</strong>.  Change of immunoglobulin G (IgG) patterns among 18 convalescent severe acute respiratory syndrome patients with a complete collection of sequential serum samples at the time points shown. The 18 patients... </a> </li> </ul> <h5>Table</h5> <ul id="tables" class="attachments ft-14"> <li> <a href="/eid/article/13/10/07-0576-t1"> <strong>Table</strong>. Cumulative rates of SARS-CoV antibodies among 176 SARS patients with known transmission histories </a> </li> </ul> <p class="topLinkStyle"> <a href="javascript:void(0)" onclick="ScrollToTop()">Top</a> </p> <a id="showLink2" onclick="showPopUp()" href="#;" title="Show Article Citations">Cite This Article</a> <p id="article-doi-footer">DOI: 10.3201/eid1310.070576</p> <p class="backTo"><a href="/eid/articles/issue/13/10/table-of-contents">Table of Contents – Volume 13, Number 10—October 2007</a></p> <div class="card bb-0 bt-0 bl-0 br-0" style="margin-top:50px;"> <div> <table id="tblSearchOptions" class="table table-bordered table-hover"> <thead> <tr> <th style="background-color:#EEE;"> EID Search Options </th> </tr> </thead> <tbody class="ft-14"> <tr> <td> <img src="/TemplatePackage/contrib/icons/standard/people_01.svg" alt="presentation_01" style="width:24px;height:24px;margin-right:3px;vertical-align:middle;"> <span style="vertical-align:middle;"><a href="/eid/AdvancedSearch"><b>Advanced Article Search</b></a> – Search articles by author and/or keyword.</span> </td> </tr> <tr> <td> <img src="/TemplatePackage/contrib/icons/standard/map_01.svg" alt="presentation_01" style="width:24px;height:24px;margin-right:3px;vertical-align:middle;"> <span style="vertical-align:middle;"><a href="/eid/ArticleMap"><b>Articles by Country Search</b></a> – Search articles by the topic country.</span> </td> </tr> <tr> <td> <img src="/TemplatePackage/contrib/icons/standard/search_01.svg" alt="presentation_01" style="width:24px;height:24px;margin-right:3px;vertical-align:middle;"> <span style="vertical-align:middle;"><a href="/eid/ArticleTypeSearch"><b>Article Type Search</b></a> – Search articles by article type and issue.</span> </td> </tr> </tbody> </table> </div> </div> <p class="topLinkStyle"> <a href="javascript:void(0)" onclick="ScrollToTop()">Top</a> </p> <div id="comment"></div> <div class="card ft-14 reader-comments" id="reader-comment"> <div class="card-header bg-primary"> Comments </div> <div id="authorcomment-formcontainer" class="card-body"> <p>Please use the form below to submit correspondence to the authors or contact them at the following address:</p> <p class="author-correspondence"> Guo-Dong Liang, State Key Laboratory for Infectious Disease Control and Prevention, Institute for Viral Disease Control and Prevention, China CDC, 100 Yingxin St, Xuanwu District, Beijing 100052, People’s Republic of China; </p> <form id="contact-form" role="form" action="/eid/submit-author-comment" method="post"> <fieldset> <div class="form-group"> <label for="returnaddress" class="lbl"><span class="required"><strong>Return Address</strong></span></label> <div class="col-sm-10"> <input id="returnaddress" name="returnaddress" type="text" class="form-control" maxlength="200" /> </div> </div> <div class="form-group"> <label for="sendTo" class="lbl"><span class="required"><strong>Send To</strong></span></label> <div class="col-sm-10"> <fieldset style="display:inline;margin-right:5px;"> <legend class="visuallyhidden">Send To</legend> <input type="radio" name="sendTo" id="sendTo_author" value="authors" checked="checked" style="height:12px;display:inline;" /> <label for="sendTo_author" style="display:inline;"> Authors</label> <input type="radio" name="sendTo" id="sendTo_editor" value="editors" style="height:12px;display:inline;margin-left:10px;" /> <label for="sendTo_editor" style="display:inline;"> Editors</label> </fieldset> </div> </div> <div class="form-group"> <label for="commenttext" class="lbl"><span class="required"><strong>Comments</strong></span></label> <div class="col-sm-10"> <textarea id="commenttext" name="commenttext" cols="20" rows="5" class="form-control" maxlength="10000"></textarea><br /> <em><span class="commenttextremaining">10000</span> character(s) remaining.</em> </div> </div> <div class="form-group"> <div class="col-sm-offset-2 col-sm-10"> <input type="submit" value="Send" id="contact-submit" class="btn btn-primary" /> </div> <input id="ia" name="ia" type="hidden" value="678" /> </fieldset> </form> </div> <div id="contact-form-success-message" style="display:none;" class="pl-3"> <p><strong>Comment submitted successfully, thank you for your feedback.</strong></p> </div> <div id="contact-form-error-message" style="display:none;" class="pl-3"> <p><strong>There was an unexpected error. 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Duration of Antibody Responses after Severe Acute Respiratory Syndrome. Emerg Infect Dis. 2007;13(10):1562-1564. https://doi.org/10.3201/eid1310.070576</td> </tr> <tr class="citationRow"> <th class="citationHeader">AMA</th> <td class="citationCell">Wu L, Wang N, Chang Y, et al. Duration of Antibody Responses after Severe Acute Respiratory Syndrome. <i>Emerging Infectious Diseases</i>. 2007;13(10):1562-1564. doi:10.3201/eid1310.070576.</td> </tr> <tr class="citationRow"> <th class="citationHeader">APA</th> <td class="citationCell">Wu, L., Wang, N., Chang, Y., Tian, X., Na, D., Zhang, L....Liang, G. (2007). Duration of Antibody Responses after Severe Acute Respiratory Syndrome. <i>Emerging Infectious Diseases</i>, <i>13</i>(10), 1562-1564. https://doi.org/10.3201/eid1310.070576.</td> </tr> </table> </div>  <div class="modal-footer"> <button id="btnCloseCitationModal" type="button" class="btn btn-outline-dark" data-dismiss="modal">Close</button> </div> </div> </div> </div> <script type="text/javascript" src="/eid/Scripts/jquery.validate.js"></script> <script type="text/javascript" src="/eid/Scripts/Contact.js?v=1.2"></script> <script type="text/javascript"> /* Javascript to add "Top" links to sections of main body */ function CreateTopLinkElement() { var p = document.createElement('p'); p.className = 'topLinkStyle'; $(p).html('<a href="#" onclick="ScrollToTop()">Top</a>'); return p; } function AppendTopLinks() { var allChildren = $('#mainbody').children(); var sections = []; for (var i = 0; i < allChildren.length; i++) { if (allChildren[i].className == 'xml-section') { sections.push(allChildren[i]); } } if (sections.length > 1) $(sections).append(CreateTopLinkElement()); } AppendTopLinks(); $(document).ready(function () { $('#pdfPopover').popover({ html: true, placement: 'top', container: $('#pdfPopover').closest('div'), content: "This file contains the article and technical appendices, not including any Excel files." }); $('#pdfPopover').on('inserted.bs.popover', function () { // CDC template js was removing close button for some reason... // so put in close button, and hook up hide on click $('#pdfPopover').closest('div').find('.popover-body').prepend("<button id='btnCloseAppendixPopover' class='close' aria-label='close'>×</button>"); $('#btnCloseAppendixPopover').click(function () { $('#pdfPopover').popover("hide"); }); }); }); </script> <script src="https://www.cdc.gov/TemplatePackage/contrib/libs/d3/d3.min.js"></script> <script src="https://www.cdc.gov/TemplatePackage/contrib/libs/c3/c3.js"></script> <div class="modal" id="eidViewsModal"> <div class="modal-dialog modal-lg"> <div class="modal-content">  <div class="modal-header"> <h4 class="modal-title">Metric Details</h4> <button type="button" class="bg-transparent border-0 h3 m-0" data-dismiss="modal" style="cursor:pointer">×</button> </div>  <div class="modal-body"> <h4 class="mt-0 mb-0">Duration of Antibody Responses after Severe Acute Respiratory Syndrome</h4> <p class="mt-0 mb-0">Volume 13, Number 10—October 2007</p> <h4 class="mt-4 open mb-0">Article Views: 5406</h4> <p>Data is collected weekly and does not include downloads and attachments. View data is from <span id="viewsRange"></span>.</p> <label for="navEidViews">Time period</label> <select id="navEidViews" class="form-control mb-4" style="max-width:250px;"> <option value="#tabFirst3">First 3 Months</option> <option value="#tabLast3">Last 3 Months</option> <option value="#tabLastYear">Last Year</option> <option value="#tabLastTwoYears">Last 2 Years</option> <option value="#tabAllData">All Data</option> </select> <div class="eid-view-panel" id="tabFirst3"><div id="eidViewsFirstThreeMonths"></div></div> <div class="eid-view-panel" id="tabLast3"><div id="eidViewsLastThreeMonths"></div></div> <div class="eid-view-panel" id="tabLastYear"><div id="eidViewsOneYear"></div></div> <div class="eid-view-panel" id="tabLastTwoYears"><div id="eidViewsLastTwoYears"></div></div> <div class="eid-view-panel" id="tabAllData"><div id="eidViewsAllData"></div></div> <h4 class="mt-4 open">Citations: <span class="mmwr_citations">310</span></h4> <div class="border-top mt-3 mb-3"></div> <div class="col-12 p-0"> <h4 class="mt-3 open">Altmetrics</h4> <div class="col-lg-4 float-left"> <div class="altmetric-embed" data-badge-details="right" data-badge-type="donut" data-condensed="true" data-hide-no-mentions="true" data-link-target="_blank"></div> <em class="small mt-3 d-block">Click a source for Altmetric details</em> </div> </div> <div class="col-lg-8 float-right"> <h5 class="open mt-0"><strong>What is the Altmetric Attention Score?</strong></h5> <p>The Altmetric Attention Score for a research output provides an indicator of the amount of attention that it has received. The score is derived from an automated algorithm, and represents a weighted count of the amount of attention Altmetric picked up for a research output.</p> </div> </div>  <div class="modal-footer"> <button type="button" class="btn btn-primary" data-dismiss="modal">Close</button> </div> </div> </div> </div> <script src="/eid/Scripts/ArticleViewsDialog.js?v=1.0"></script> <script> ArticleViews.data = [ { Views: 1, Date: new Date("2019-07-27" + "T00:00:00") }, { Views: 0, Date: new Date("2019-08-03" + "T00:00:00") }, { Views: 0, Date: new Date("2019-08-10" + "T00:00:00") }, { Views: 1, Date: new Date("2019-08-17" + "T00:00:00") }, { Views: 0, Date: new Date("2019-08-24" + "T00:00:00") }, { Views: 2, Date: new Date("2019-08-31" + "T00:00:00") }, { Views: 0, Date: new Date("2019-09-07" + "T00:00:00") }, { Views: 2, Date: new Date("2019-09-14" + "T00:00:00") }, { Views: 3, Date: new Date("2019-09-21" + "T00:00:00") }, { Views: 0, Date: new Date("2019-09-28" + "T00:00:00") }, { Views: 0, 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