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<?covid-19-tdm?>
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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JMIR</journal-id>
      <journal-id journal-id-type="nlm-ta">J Med Internet Res</journal-id>
      <journal-title>Journal of Medical Internet Research</journal-title>
      <issn pub-type="epub">1438-8871</issn>
      <publisher>
        <publisher-name>JMIR Publications</publisher-name>
        <publisher-loc>Toronto, Canada</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">v22i8e20914</article-id>
      <article-id pub-id-type="pmid">32707538</article-id>
      <article-id pub-id-type="doi">10.2196/20914</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Paper</subject>
        </subj-group>
        <subj-group subj-group-type="article-type">
          <subject>Original Paper</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>The Infection Rate of COVID-19 in Wuhan, China: Combined Analysis of Population Samples</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Eysenbach</surname>
            <given-names>Gunther</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Zhang</surname>
            <given-names>Wenhui</given-names>
          </name>
        </contrib>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Banik</surname>
            <given-names>Palash</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib id="contrib1" contrib-type="author">
          <name name-style="western">
            <surname>Qu</surname>
            <given-names>Hui-Qi</given-names>
          </name>
          <degrees>MD, PhD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0001-9317-4488</ext-link>
        </contrib>
        <contrib id="contrib2" contrib-type="author">
          <name name-style="western">
            <surname>Cheng</surname>
            <given-names>Zhangkai Jason</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <xref rid="aff2" ref-type="aff">2</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-8621-4119</ext-link>
        </contrib>
        <contrib id="contrib3" contrib-type="author">
          <name name-style="western">
            <surname>Duan</surname>
            <given-names>Zhifeng</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <xref rid="aff3" ref-type="aff">3</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-4880-1662</ext-link>
        </contrib>
        <contrib id="contrib4" contrib-type="author">
          <name name-style="western">
            <surname>Tian</surname>
            <given-names>Lifeng</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0003-1880-5811</ext-link>
        </contrib>
        <contrib id="contrib5" contrib-type="author" corresp="yes">
          <name name-style="western">
            <surname>Hakonarson</surname>
            <given-names>Hakon</given-names>
          </name>
          <degrees>MD, PhD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <address>
            <institution>Center for Applied Genomics</institution>
            <institution>The Children’s Hospital of Philadelphia</institution>
            <addr-line>3615 Civic Center Boulevard</addr-line>
            <addr-line>Philadelphia, PA</addr-line>
            <country>United States</country>
            <phone>1 267 426 0088</phone>
            <email>Hakonarson@email.chop.edu</email>
          </address>
          <xref rid="aff4" ref-type="aff">4</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0003-2814-7461</ext-link>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution>Center for Applied Genomics</institution>
        <institution>The Children’s Hospital of Philadelphia</institution>
        <addr-line>Philadelphia, PA</addr-line>
        <country>United States</country>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution>Department of Radiation Oncology</institution>
        <institution>Sun Yat-sen University Cancer Center</institution>
        <addr-line>Guangzhou</addr-line>
        <country>China</country>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution>Institute of Allergy and Immunology</institution>
        <institution>School of Medicine</institution>
        <institution>Shenzhen University</institution>
        <addr-line>Shenzhen</addr-line>
        <country>China</country>
      </aff>
      <aff id="aff4">
        <label>4</label>
        <institution>Divisions of Human Genetics and Pulmonary Medicine</institution>
        <institution>The Perelman School of Medicine</institution>
        <institution>University of Pennsylvania</institution>
        <addr-line>Philadelphia, PA</addr-line>
        <country>United States</country>
      </aff>
      <author-notes>
        <corresp>Corresponding Author: Hakon Hakonarson <email>Hakonarson@email.chop.edu</email></corresp>
      </author-notes>
      <pub-date pub-type="collection">
        <month>8</month>
        <year>2020</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>14</day>
        <month>8</month>
        <year>2020</year>
      </pub-date>
      <volume>22</volume>
      <issue>8</issue>
      <elocation-id>e20914</elocation-id>
      <history>
        <date date-type="received">
          <day>4</day>
          <month>6</month>
          <year>2020</year>
        </date>
        <date date-type="rev-request">
          <day>18</day>
          <month>7</month>
          <year>2020</year>
        </date>
        <date date-type="rev-recd">
          <day>18</day>
          <month>7</month>
          <year>2020</year>
        </date>
        <date date-type="accepted">
          <day>22</day>
          <month>7</month>
          <year>2020</year>
        </date>
      </history>
      <copyright-statement>©Hui-Qi Qu, Zhangkai Jason Cheng, Zhifeng Duan, Lifeng Tian, Hakon Hakonarson. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 14.08.2020.</copyright-statement>
      <copyright-year>2020</copyright-year>
      <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/">
        <p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in the Journal of Medical Internet Research, is properly cited. The complete bibliographic information, a link to the original publication on http://www.jmir.org/, as well as this copyright and license information must be included.</p>
      </license>
      <self-uri xlink:href="https://www.jmir.org/2020/8/e20914" xlink:type="simple"/>
      <abstract>
        <sec sec-type="background">
          <title>Background</title>
          <p>The coronavirus disease (COVID-19) pandemic began in Wuhan, China, in December 2019. Wuhan had a much higher mortality rate than the rest of China. However, a large number of asymptomatic infections in Wuhan may have never been diagnosed, contributing to an overestimated mortality rate.</p>
        </sec>
        <sec sec-type="objective">
          <title>Objective</title>
          <p>This study aims to obtain an accurate estimate of infections in Wuhan using internet data.</p>
        </sec>
        <sec sec-type="methods">
          <title>Methods</title>
          <p>In this study, we performed a combined analysis of the infection rate among evacuated foreign citizens to estimate the infection rate in Wuhan in late January and early February.</p>
        </sec>
        <sec sec-type="results">
          <title>Results</title>
          <p>Based on our analysis, the combined infection rate of the foreign evacuees was 0.013 (95% CI 0.008-0.022). Therefore, we estimate the number of infected people in Wuhan to be 143,000 (range 88,000-242,000), which is significantly higher than previous estimates. Our study indicates that a large number of infections in Wuhan were not diagnosed, which has resulted in an overestimated case fatality rate.</p>
        </sec>
        <sec sec-type="conclusions">
          <title>Conclusions</title>
          <p>Increased awareness of the original infection rate of Wuhan is critical for proper public health measures at all levels, as well as to eliminate panic caused by overestimated mortality rates that may bias health policy actions by the authorities.</p>
        </sec>
      </abstract>
      <kwd-group>
        <kwd>infectious disease</kwd>
        <kwd>COVID-19</kwd>
        <kwd>infection rate</kwd>
        <kwd>China</kwd>
        <kwd>Wuhan</kwd>
        <kwd>fatality</kwd>
        <kwd>public health</kwd>
        <kwd>diagnosis</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="introduction">
      <title>Introduction</title>
      <p>In December 2019, the first cases of coronavirus disease (COVID-19) were reported in Wuhan, China, a megacity with a population of approximately 11 million people. To prevent the spread of this highly infectious disease, the government initiated a city-wide lockdown on January 23, 2020. However, despite these efforts, COVID-19 spread to many countries across the world, reaching pandemic levels, and continues to be a serious public health concern due to its high mortality rate. According to the large-sample analysis by Wu and McGoogan [<xref ref-type="bibr" rid="ref1">1</xref>], China’s case fatality rate (CFR) was 2.3%—that is, 1023 deaths from 44,672 confirmed cases as of February 11, 2020, with a significant proportion of cases originating from Wuhan. The large number of infected people in Wuhan put a tight strain on essential medical resources. The city had a much higher mortality rate (according to Feb 10th statistics: CFR=4.05% [748 deaths/18,454 diagnoses]; Apr 24th statistics: CFR=7.69% [3869 deaths/50,333 diagnoses]) than the rest of China. The overall CFR of 2.3% for China was likely overestimated, due to strained medical resources and a large number of undiagnosed patients. According to a recent study, 78% of those who had been infected were asymptomatic [<xref ref-type="bibr" rid="ref2">2</xref>]. Therefore, a large number of asymptomatic infections in Wuhan might have never been diagnosed, which contributed to the overestimated CFR. An accurate estimation of the infection rate is therefore important to assess Wuhan’s CFR precisely.</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <p>Using Markov Chain Monte Carlo methods, Wu et al [<xref ref-type="bibr" rid="ref3">3</xref>] estimated that 75,815 individuals (95% CI 37,304-130,330) had been infected in Wuhan as of January 25, 2020. Following this, a number of foreign governments evacuated their citizens and performed thorough etiological tests on them. This group of evacuees can serve as a “random” sample to estimate the infection rate in Wuhan. With internet search as an important source of epidemiologic information on COVID-19 [<xref ref-type="bibr" rid="ref4">4</xref>], we performed a combined analysis of the infection rates of these population samples using publicly available data (<xref ref-type="table" rid="table1">Table 1</xref>), instead of a simple pooled calculation, considering potential differences in lifestyles and pathogen exposure across different populations. The combined analysis was done using the Comprehensive Meta-Analysis Software (Biostat, Inc).</p>
      <table-wrap position="float" id="table1">
        <label>Table 1</label>
        <caption>
          <p>Number of infected people from different countries.</p>
        </caption>
        <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
          <col width="210"/>
          <col width="210"/>
          <col width="270"/>
          <col width="310"/>
          <thead>
            <tr valign="top">
              <td>Country</td>
              <td>Evacuation date</td>
              <td>Confirmed cases (n=14), n</td>
              <td>Evacuees (n=1401), n</td>
            </tr>
          </thead>
          <tbody>
            <tr valign="bottom">
              <td>Japan [<xref ref-type="bibr" rid="ref5">5</xref>]</td>
              <td>N/A<sup>a</sup></td>
              <td>9</td>
              <td>566</td>
            </tr>
            <tr valign="top">
              <td>Korea [<xref ref-type="bibr" rid="ref6">6</xref>-<xref ref-type="bibr" rid="ref8">8</xref>]</td>
              <td>January 31, 2020</td>
              <td>1</td>
              <td>368</td>
            </tr>
            <tr valign="top">
              <td>Germany [<xref ref-type="bibr" rid="ref9">9</xref>]</td>
              <td>February 1, 2020</td>
              <td>2</td>
              <td>124</td>
            </tr>
            <tr valign="top">
              <td>Singapore [<xref ref-type="bibr" rid="ref10">10</xref>-<xref ref-type="bibr" rid="ref12">12</xref>]</td>
              <td>January 30, 2020</td>
              <td>1</td>
              <td>92</td>
            </tr>
            <tr valign="top">
              <td>Italy [<xref ref-type="bibr" rid="ref13">13</xref>]</td>
              <td>February 2, 2020</td>
              <td>1</td>
              <td>56</td>
            </tr>
            <tr valign="top">
              <td>United States [<xref ref-type="bibr" rid="ref14">14</xref>]</td>
              <td>January 29, 2020</td>
              <td>0</td>
              <td>195</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="table1fn1">
            <p><sup>a</sup>N/A: not applicable.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>Our analysis demonstrates that there is no significant heterogeneity across different population samples (heterogeneity test <italic>P</italic>=.491). The combined infection rate is 0.013 (95% CI 0.008-0.022) (<xref rid="figure1" ref-type="fig">Figure 1</xref>). Based on our results, we estimate the number of infected people in Wuhan, China, to be 143,000 (range 88,000-242,000), which is significantly higher than the estimate proposed by Wu et al [<xref ref-type="bibr" rid="ref3">3</xref>].</p>
      <fig id="figure1" position="float">
        <label>Figure 1</label>
        <caption>
          <p>Combined analysis of infection rates of different populations.</p>
        </caption>
        <graphic xlink:href="jmir_v22i8e20914_fig1.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
      </fig>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>Our estimate indicates that a large number of infections in Wuhan were not diagnosed. The number of undiagnosed cases in late January and early February is larger than the final diagnosed count reported to date (n=50,333), which has resulted in an overestimated CFR. In addition, our study suggests that the lower CFR (0.51%) estimated by the Centre for Evidence-Based Medicine [<xref ref-type="bibr" rid="ref15">15</xref>] does not indicate viral variants and loss of virulence. Taken together, increased awareness of the original infection rates in Wuhan, China, is critically important for appropriate public health measures at all levels, as well as to eliminate panic caused by overestimated mortality rates that may bias health policy actions by the authorities.</p>
    </sec>
  </body>
  <back>
    <app-group/>
    <glossary>
      <title>Abbreviations</title>
      <def-list>
        <def-item>
          <term id="abb1">COVID-19</term>
          <def>
            <p>coronavirus disease</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb2">CFR</term>
          <def>
            <p>case fatality rate</p>
          </def>
        </def-item>
      </def-list>
    </glossary>
    <ack>
      <p>The study was supported by Institutional Development Funds from the Children’s Hospital of Philadelphia to the Center for Applied Genomics, The Children’s Hospital of Philadelphia Endowed Chair in Genomic Research to HH.</p>
    </ack>
    <fn-group>
      <fn fn-type="con">
        <p>HQ was responsible for the literature search, study design, data collection, data analysis, data interpretation, and writing; ZJC was involved in data collection; ZD in data interpretation; LT in study design and data interpretation; and HH in study design, data interpretation, and writing.</p>
      </fn>
      <fn fn-type="conflict">
        <p>None declared.</p>
      </fn>
    </fn-group>
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