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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Public Health</journal-id>
<journal-title>Frontiers in Public Health</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Public Health</abbrev-journal-title>
<issn pub-type="epub">2296-2565</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fpubh.2023.1271917</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Public Health</subject>
<subj-group>
<subject>Data Report</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Levels of antibodies to SARS-CoV-2 at key time points during the COVID-19 pandemic in China</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Lina</surname> <given-names>Liu</given-names></name>
<role content-type="https://credit.niso.org/contributor-roles/data-curation/"/>
<role content-type="https://credit.niso.org/contributor-roles/formal-analysis/"/>
<role content-type="https://credit.niso.org/contributor-roles/investigation/"/>
<role content-type="https://credit.niso.org/contributor-roles/methodology/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name><surname>Hui</surname> <given-names>Liu</given-names></name>
<xref ref-type="corresp" rid="c001"><sup>&#x0002A;</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/1597668/overview"/>
<role content-type="https://credit.niso.org/contributor-roles/conceptualization/"/>
<role content-type="https://credit.niso.org/contributor-roles/formal-analysis/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-original-draft/"/>
<role content-type="https://credit.niso.org/contributor-roles/writing-review-editing/"/>
</contrib>
</contrib-group>
<aff><institution>Department of Laboratory and Quarantine, Dalian Medical University</institution>, <addr-line>Dalian</addr-line>, <country>China</country></aff>
<author-notes>
<fn fn-type="edited-by"><p>Edited by: Jos&#x000E9; Tuells, University of Alicante, Spain</p></fn>
<fn fn-type="edited-by"><p>Reviewed by: Ming Zheng, Academy of Military Medical Sciences, China; Diego Cantoni, MRC-University of Glasgow Centre for Virus Research (MRC), United Kingdom</p></fn>
<corresp id="c001">&#x0002A;Correspondence: Liu Hui <email>liuhui60&#x00040;dmu.edu.cn</email></corresp>
</author-notes>
<pub-date pub-type="epub">
<day>22</day>
<month>11</month>
<year>2023</year>
</pub-date>
<pub-date pub-type="collection">
<year>2023</year>
</pub-date>
<volume>11</volume>
<elocation-id>1271917</elocation-id>
<history>
<date date-type="received">
<day>03</day>
<month>08</month>
<year>2023</year>
</date>
<date date-type="accepted">
<day>03</day>
<month>11</month>
<year>2023</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x000A9; 2023 Lina and Hui.</copyright-statement>
<copyright-year>2023</copyright-year>
<copyright-holder>Lina and Hui</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p></license>
</permissions>
<kwd-group>
<kwd>COVID-19</kwd>
<kwd>SARS-CoV-2</kwd>
<kwd>antibody</kwd>
<kwd>vaccination</kwd>
<kwd>public health</kwd>
</kwd-group>
<counts>
<fig-count count="1"/>
<table-count count="1"/>
<equation-count count="0"/>
<ref-count count="15"/>
<page-count count="4"/>
<word-count count="2067"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Infectious Diseases: Epidemiology and Prevention</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec id="s1">
<title>1 Introduction</title>
<p>Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a worldwide public health problem that has occurred in recent years. SARS-CoV-2 is found mainly in the respiratory secretions of patients infected with COVID-19. These infected patients are also the main source of transmission, which occurs primarily through the respiratory tract (<xref ref-type="bibr" rid="B1">1</xref>). When the virus enters the trachea, the mucosal cells that make up the tracheal surface secrete mucus to encapsulate the virus, which is then propelled by cilia toward the larynx or nose for expulsion. However, COVID-19 is characterized by a dry cough rather than expectoration, suggesting that the virus has crossed the trachea and traveled through the bronchi to the alveoli. The virus enters the alveoli, infects the alveolar cells, and begins to multiply. Immune cells, e.g., macrophages, kill the infected lung cells and engulf the debris, and any remaining debris that is not engulfed needs to be expelled by coughing (<xref ref-type="bibr" rid="B2">2</xref>, <xref ref-type="bibr" rid="B3">3</xref>). At the same time, specific immunity can be triggered to produce antibodies and other immune substances, resulting in most people being cured. However, a small proportion of patients experience disease exacerbation, even resulting in death (<xref ref-type="bibr" rid="B4">4</xref>, <xref ref-type="bibr" rid="B5">5</xref>).</p>
<p>From a population perspective, the population was not immune to SARS-CoV-2 before 2019 because SARS-CoV-2 is a novel virus. Pneumonia of unknown origin (later named COVID-19) was detected on December 08, 2019 in Wuhan, China (<xref ref-type="bibr" rid="B6">6</xref>). As of January 30, 2020, there were 12,050 cases of COVID-19 (confirmed) and 259 deaths in China, with a mortality rate of 2.1% (<xref ref-type="bibr" rid="B7">7</xref>).</p>
<p>After January 20, 2020, mainland China adopted the highest level of prevention and control measures, as well as a &#x0201C;zero-COVID&#x0201D; policy, including comprehensive screening of infection sources (asymptomatic infected persons), strict quarantine measures, closure of schools and places where people congregate, wearing of masks, and disinfection of public places. After April 2020, the outbreak of COVID-19 was largely contained, with only a few disseminated cases remaining (<xref ref-type="bibr" rid="B7">7</xref>).</p>
<p>COVID-19 vaccines were successfully developed and widely used since 2021, and the vaccination rate (inactivated vaccine) in mainland China exceeded 90% by the middle of 2021 (<xref ref-type="bibr" rid="B8">8</xref>). However, mainland China-mainland continued with the highest level of prevention and control measures/&#x0201C;zero-COVID&#x0201D; until the end of 2022. The peak incidence of COVID-19 occurred in late 2022 and early 2023, ending with a peak at end of January 2023, because mainland China no longer adhered to the highest level of prevention and control measures/&#x0201C;zero-COVID&#x0201D;.</p>
<p>Throughout the course of the COVID-19 epidemic, mainland China adopted a variety of preventive and control measures, including non-pharmacological control (administrative interventions) and vaccination. Thus, mainland China is an excellent model to observe the course of the epidemic and evaluate the various preventive and control measures. This article provides SARS-CoV-2 antibody data at major time points during the COVID-19 epidemic in China to provide a scientific basis to study the prevalence of COVID-19 and evaluate various preventive and control measures.</p></sec>
<sec id="s2">
<title>2 Materials and methods</title>
<p>Antibody data from the beginning of 2020 were obtained from published literature (<xref ref-type="bibr" rid="B9">9</xref>&#x02013;<xref ref-type="bibr" rid="B11">11</xref>). Data from the first half of 2022 and the first half of 2023 were obtained from measured antibody levels. The antibody test samples (serum) were obtained hospitalized patients in The Second Hospital of Dalian Medical University. All patients were free of COVID-19 infection or other infection within 1 week before examination and all had received more than one COVID-19 vaccination. In the 2022 group, the average age of the patients was 58.9 &#x000B1; 19.1 years old, and there were 517 men and 314 women. In the 2023 group, the average age was 58.9 &#x000B1; 17.2 years old, and there were 897 men and 960 women. The levels of total antibody to SARS-CoV-2 were tested using a chemiluminescence-based method, and a cutoff value &#x0003E;1.00 was considered positive.</p>
<p>Non-normally distributed data were reported as the median and interquartile range. The significance of differences was determined by Kruskal&#x02013;Wallis H tests using SPSS software. A value of <italic>P</italic> &#x0003C;0.05 (bilateral) was considered statistical significance.</p></sec>
<sec id="s3">
<title>3 Results and discussion</title>
<p>The beginning of 2020 data showed that the population antibody positivity rate was 3.2&#x02013;6.9% (3.9 were suggested due to relatively large sample size). SARS-CoV-2 was a new virus and the population was not immune; therefore, these data suggest that around 3.9% of the population was infected with COVID-19.</p>
<p>After the successful development of the vaccine by the end of 2020, the vaccination rate in mainland China exceeded 90% in the end of 2021 (<xref ref-type="bibr" rid="B8">8</xref>). Our test data shows that the antibody positive rate of a mainland China (Dalian) population after vaccination was 46.6% in the first half of 2022, as shown in <xref ref-type="fig" rid="F1">Figure 1</xref>. Compared with the pre-vaccination period, in which the antibody positivity rate in mainland China was about 3.9%, while mainland China adopted strict control measures and monitoring positive cases (usually daily testing for key populations; if found positive, immediate population-wide testing); therefore, this result indicated that the antibody positivity rate in the first half of 2022 comes mainly from vaccination rather than from natural infection.</p>
<fig id="F1" position="float">
<label>Figure 1</label>
<caption><p>Positive rate of antibody to SARS-CoV-2 at key time points during the COVID-19 pandemic in China.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fpubh-11-1271917-g0001.tif"/>
</fig>
<p>At the end of 2022, the Chinese government adopted normalized prevention and control and relaxed the strict control measures. As a result, the peak incidence of COVID-19 occurred in early 2023. Our data showed that the antibody positivity rate in mainland China (Dalian) was 82.4% in the first half of 2023 after the Chinese government adopted normalized control measures (<xref ref-type="fig" rid="F1">Figure 1</xref>). Obviously, natural infection played an important role in the increase in antibody levels.</p>
<p>We also performed quantitative antibody tests on the antibody-positive population. We found that the level of antibodies to SARS-CoV-2 in early 2023 was significantly higher than that in the January 2022 (derived from the vaccine), as shown in <xref ref-type="table" rid="T1">Table 1</xref>, indicating that the antibodies detected in early 2023 could mainly derived from natural infection.</p>
<table-wrap position="float" id="T1">
<label>Table 1</label>
<caption><p>Quantitative antibody to SARS-CoV-2 on the antibody-positive population.</p></caption>
<table frame="box" rules="all">
<thead>
<tr style="background-color:&#x00023;919498;color:&#x00023;ffffff">
<th valign="top" align="left"><bold>Times</bold></th>
<th valign="top" align="center" colspan="3"><bold>Quartile</bold></th>
<th valign="top" align="center"><bold><italic>Z-</italic>value</bold></th>
<th valign="top" align="center"><bold><italic>P-</italic>value</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td/>
<td valign="top" align="center"><bold>25th</bold></td>
<td valign="top" align="center"><bold>50th</bold></td>
<td valign="top" align="center"><bold>75th</bold></td>
<td/>
<td/>
</tr>
<tr>
<td valign="top" align="left">First half of 2022</td>
<td valign="top" align="center">4.520</td>
<td valign="top" align="center">10.210</td>
<td valign="top" align="center">25.260</td>
<td valign="top" align="center">13.785</td>
<td valign="top" align="center">&#x0003C; 0.001</td>
</tr>
 <tr>
<td valign="top" align="left">First half of 2023</td>
<td valign="top" align="center">7.773</td>
<td valign="top" align="center">68.660</td>
<td valign="top" align="center">152.970</td>
<td/>
<td/>
</tr></tbody>
</table>
</table-wrap>
<p>Despite the many variants of SARS-CoV-2, neutralizing antibodies were effective against most of them, and no new serotypes have been identified (<xref ref-type="bibr" rid="B12">12</xref>&#x02013;<xref ref-type="bibr" rid="B14">14</xref>). The total antibodies were measured in present study, thus the variants could have little effect on the rate of antibody to SARS-CoV-2 in the population.</p>
<p>The immune imprinting effect is important. Because most countries in the world did not use the Zero-COVID-19 policy as the Chinese government did, the previous study used clinical cohorts whose immune histories are too complex to trace. Thus, Chinese cohort is very &#x0201C;clean&#x0201D; for the study of the immune imprint effect. The quantitative results of the positive antibodies to SARS-CoV-2 had also been provided in present study, which could be used as a reference for the study of the immune imprint effect.</p>
<p>The limitation of this paper is that a population antibody positivity rate of 82.4% does not completely exclude vaccination as the source. However, inactivated vaccines are generally considered to be less effective (<xref ref-type="bibr" rid="B15">15</xref>) and show limited interference with antibodies produced by natural infection; thus, the data in this paper remain of great value.</p></sec>
<sec sec-type="data-availability" id="s4">
<title>Data availability statement</title>
<p>The original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.</p></sec>
<sec sec-type="ethics-statement" id="s5">
<title>Ethics statement</title>
<p>Ethical approval was not required for the study involving humans in accordance with the local legislation and institutional requirements. Written informed consent to participate in this study was not required from the participants or the participants&#x00027; legal guardians/next of kin in accordance with the national legislation and the institutional requirements.</p></sec>
<sec sec-type="author-contributions" id="s6">
<title>Author contributions</title>
<p>LL: Data curation, Formal analysis, Investigation, Methodology, Writing&#x02014;original draft. LH: Conceptualization, Formal analysis, Writing&#x02014;original draft, Writing&#x02014;review &#x00026; editing.</p></sec>
</body>
<back>
<sec sec-type="funding-information" id="s7">
<title>Funding</title>
<p>The author(s) declare that no financial support was received for the research, authorship, and/or publication of this article.</p>
</sec>
<sec sec-type="COI-statement" id="conf1">
<title>Conflict of interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="disclaimer" id="s8">
<title>Publisher&#x00027;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
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