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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">aard</journal-id>
<journal-title-group>
<journal-title>Allergy, Asthma &#x0026; Respiratory Disease</journal-title>
<abbrev-journal-title>Allergy Asthma Respir Dis</abbrev-journal-title>
</journal-title-group>
<issn pub-type="ppub">2288-0402</issn>
<issn pub-type="epub">2288-0410</issn>
<publisher>
<publisher-name>The Korean Academy of Pediatric Allergy and Respiratory Disease; The Korean Academy of Asthma</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.4168/aard.2018.6.1.47</article-id>
<article-id pub-id-type="publisher-id">aard-6-47</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Original Article</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Bronchiolitis severity according to the infected viruses</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name name-style="western" xml:lang="en">
<surname>Lee</surname><given-names>Su Jin</given-names></name>
</contrib>
<contrib contrib-type="author">
<name name-style="western" xml:lang="en">
<surname>Park</surname><given-names>Sang Kyu</given-names></name>
<xref ref-type="aff" rid="aff1-aard-6-47"/>
</contrib>
<contrib contrib-type="author">
<name name-style="western" xml:lang="en">
<surname>Kim</surname><given-names>Ji Hyun</given-names></name>
<xref ref-type="corresp" rid="c1-aard-6-47"/>
<xref ref-type="aff" rid="aff1-aard-6-47"/>
</contrib>
<contrib contrib-type="author">
<name name-style="western" xml:lang="en">
<surname>Cho</surname><given-names>Sung Min</given-names></name>
<xref ref-type="aff" rid="aff1-aard-6-47"/>
</contrib>
<aff id="aff1-aard-6-47" xml:lang="en">Department of Pediatrics, Dongguk University Ilsan Hospital, Goyang, Korea</aff>
</contrib-group>
<author-notes>
<corresp id="c1-aard-6-47">Correspondence to: Ji Hyun Kim https://orcid.org/0000-0001-8493-2881 Department of Pediatrics, Dongguk University Ilsan Hospital, 27 Dongguk-ro, Ilsandong-gu, Goyang 10326, Korea Tel: +82-31-961-7190, Fax: +82-31-961-7188, E-mail: <email>eogurdl@gmail.com</email></corresp>
</author-notes>
<pub-date pub-type="ppub"><month>1</month><year>2018</year></pub-date>
<pub-date pub-type="epub"><day>5</day><month>1</month><year>2018</year></pub-date>
<volume>6</volume><issue>1</issue>
<fpage>47</fpage><lpage>53</lpage>
<history>
<date date-type="received"><day>10</day><month>03</month><year>2017</year></date>
<date date-type="revised"><day>24</day><month>10</month><year>2017</year></date>
<date date-type="accepted"><day>24</day><month>10</month><year>2017</year></date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2018 The Korean Academy of Pediatric Allergy and Respiratory Disease; The Korean Academy of Asthma</copyright-statement>
<copyright-year>2018</copyright-year>
<license><license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (<ext-link ext-link-type="uri" xlink:href="http://creativecommons.org/licenses/by-nc/4.0/">http://creativecommons.org/licenses/by-nc/4.0/</ext-link>) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p></license>
</permissions>
<abstract xml:lang="en">
<sec>
<title>Purpose</title>
<p>The aim of this study was to evaluate the severity of disease in children with acute bronchiolitis according to the type of infected virus.</p>
</sec>
<sec>
<title>Methods</title>
<p>From November 2007 to May 2015, 768 patients under 2 years of age who underwent real time-polymerase chain reaction of nasopharyngeal aspirates admitted to the Department of Pediatrics of Dongguk University Ilsan Hospital for acute bronchiolitis were enrolled. Severe bronchiolitis was defined as presence of one or more kinds among tachypnea, chest retraction, needs of O<sc>2</sc> inhalation or ventilator care.</p>
</sec>
<sec>
<title>Results</title>
<p>The severity of bronchiolitis was increased with shorter fever duration (<italic>P</italic> &#x003C;0.001) and previous wheezing episodes (<italic>P</italic> =0.005). In the case of single infection, respiratory syncytial virus (RSV) A only increased the severity of acute bronchiolitis (<italic>P</italic> =0.012). However, the severity of illness decreased when RSV A coinfected with adenovirus (<italic>P</italic> =0.034), human rhinovirus (<italic>P</italic>=0.038), or human coronavirus NL63 (<italic>P</italic>=0.042). On the other hand, when human rhinovirus was coinfected with enterovirus (<italic>P</italic>=0.013) or parainfluenza 3 (<italic>P</italic>=0.019), the severity was increased. When human metapneumovirus coinfected with human bocavirus, the severity was increased (<italic>P</italic>=0.038).</p>
</sec>
<sec>
<title>Conclusion</title>
<p>Acute bronchiolitis was associated with increased severity only when RSV A infected solely, but several viruses increased or decreased the severity when coinfection occurred. Therefore, it may be helpful in predicting the course of the acute bronchiolitis according to the affected virus.</p>
</sec>
</abstract>
<kwd-group xml:lang="en">
<kwd>Bronchiolitis</kwd>
<kwd>Infant</kwd>
<kwd>Respiratory syncytial virus</kwd>
<kwd>Severity</kwd>
</kwd-group>
</article-meta>
</front>
<back>
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</ref-list>
<sec sec-type="display-objects">
<title>Figures and Tables</title>
<fig id="F1-aard-6-47" position="anchor">
<label>Fig. 1.</label>
<caption xml:lang="en"><p>Year-round change of acute bronchiolitis with 16 respiratory viruses isolated for 768 hospitalized children.</p></caption>
<graphic xlink:href="aard-6-47f1.tif"/>
</fig>
<table-wrap id="T1-aard-6-47" position="float">
<label>Table 1.</label>
<caption xml:lang="en"><p>Clinical characteristics of hospitalized children with acute bronchiolitis</p></caption>
<table frame="hsides" rules="all">
<thead>
<tr>
<th valign="middle" align="left">Characteristic</th>
<th valign="middle" align="center">Number (%)</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="middle" align="left">Sex</td>
<td valign="middle" align="center">&#x00A0;</td>
</tr>
<tr>
<td valign="middle" align="left">&#x2003;Female</td>
<td valign="middle" align="center">287 (37.4)</td>
</tr>
<tr>
<td valign="middle" align="left">&#x2003;Male</td>
<td valign="middle" align="center">481 (62.6)</td>
</tr>
<tr>
<td valign="middle" align="left">Age (yr)</td>
<td valign="middle" align="center">&#x00A0;</td>
</tr>
<tr>
<td valign="middle" align="left">&#x2003;&#x2264;1</td>
<td valign="middle" align="center">583 (75.9)</td>
</tr>
<tr>
<td valign="middle" align="left">&#x2003;&#x003E;1, &#x003C;2</td>
<td valign="middle" align="center">185 (24.1)</td>
</tr>
<tr>
<td valign="middle" align="left">Hospitalization period (day)</td>
<td valign="middle" align="center">&#x00A0;</td>
</tr>
<tr>
<td valign="middle" align="left">&#x2003;&#x003C;3</td>
<td valign="middle" align="center">96 (12.5)</td>
</tr>
<tr>
<td valign="middle" align="left">&#x2003;4</td>
<td valign="middle" align="center">188 (24.5)</td>
</tr>
<tr>
<td valign="middle" align="left">&#x2003;5</td>
<td valign="middle" align="center">169 (22)</td>
</tr>
<tr>
<td valign="middle" align="left">&#x2003;6</td>
<td valign="middle" align="center">132 (17.2)</td>
</tr>
<tr>
<td valign="middle" align="left">&#x2003;7</td>
<td valign="middle" align="center">58 (7.6)</td>
</tr>
<tr>
<td valign="middle" align="left">&#x2003;&#x2265;8</td>
<td valign="middle" align="center">125 (16.3)</td>
</tr>
<tr>
<td valign="middle" align="left">Fever (day)</td>
<td valign="middle" align="center">&#x00A0;</td>
</tr>
<tr>
<td valign="middle" align="left">&#x2003;None</td>
<td valign="middle" align="center">343 (44.7)</td>
</tr>
<tr>
<td valign="middle" align="left">&#x2003;1</td>
<td valign="middle" align="center">94 (12.2)</td>
</tr>
<tr>
<td valign="middle" align="left">&#x2003;2</td>
<td valign="middle" align="center">86 (11.2)</td>
</tr>
<tr>
<td valign="middle" align="left">&#x2003;&#x2265;3</td>
<td valign="middle" align="center">245 (31.8)</td>
</tr>
<tr>
<td valign="middle" align="left">Ventilator care, yes</td>
<td valign="middle" align="center">62 (8.1)</td>
</tr>
<tr>
<td valign="middle" align="left">Siblings, yes</td>
<td valign="middle" align="center">440 (57.3)</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="T2-aard-6-47" position="float">
<label>Table 2.</label>
<caption xml:lang="en"><p>Clinical characteristics of hospitalized children with acute bronchiolitis analyzed according to disease severity</p></caption>
<table frame="hsides" rules="all">
<thead>
<tr>
<th valign="middle" align="left">Characteristic</th>
<th valign="middle" align="center">Nonsevere (n=269)</th>
<th valign="middle" align="center">Severe (n=499)</th>
<th valign="middle" align="center"><italic>P</italic>-value</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="middle" align="left">Age (mo)<xref ref-type="table-fn" rid="table2-fn3-aard-6-47">&#x2217;</xref></td>
<td valign="middle" align="center">3.39</td>
<td valign="middle" align="center">2.62</td>
<td valign="middle" align="center">0.054</td>
</tr>
<tr>
<td valign="middle" align="left">Hospitalization period (day)<xref ref-type="table-fn" rid="table2-fn3-aard-6-47">&#x2217;</xref></td>
<td valign="middle" align="center">4.2</td>
<td valign="middle" align="center">6.35</td>
<td valign="middle" align="center">&#x003C;0.001</td>
</tr>
<tr>
<td valign="middle" align="left">Fever (day)<xref ref-type="table-fn" rid="table2-fn3-aard-6-47">&#x2217;</xref></td>
<td valign="middle" align="center">2.20</td>
<td valign="middle" align="center">1.60</td>
<td valign="middle" align="center">&#x003C;0.001</td>
</tr>
<tr>
<td valign="middle" align="left">ICU hospitalization (day)<xref ref-type="table-fn" rid="table2-fn3-aard-6-47">&#x2217;</xref></td>
<td valign="middle" align="center">0</td>
<td valign="middle" align="center">0.05</td>
<td valign="middle" align="center">0.001</td>
</tr>
<tr>
<td valign="middle" align="left">CRP (mg/dL)<xref ref-type="table-fn" rid="table2-fn3-aard-6-47">&#x2217;</xref></td>
<td valign="middle" align="center">1.05</td>
<td valign="middle" align="center">1.20</td>
<td valign="middle" align="center">0.261</td>
</tr>
<tr>
<td valign="middle" align="left">Lymphocyte (%)<xref ref-type="table-fn" rid="table2-fn3-aard-6-47">&#x2217;</xref></td>
<td valign="middle" align="center">55.99</td>
<td valign="middle" align="center">52.94</td>
<td valign="middle" align="center">0.006</td>
</tr>
<tr>
<td valign="middle" align="left">Male sex<sup><xref ref-type="table-fn" rid="table2-fn4-aard-6-47">&#x2020;</xref></sup></td>
<td valign="middle" align="center">160 (59.5)</td>
<td valign="middle" align="center">321 (64.3)</td>
<td valign="middle" align="center">0.185</td>
</tr>
<tr>
<td valign="middle" align="left">Siblings, yes<sup><xref ref-type="table-fn" rid="table2-fn4-aard-6-47">&#x2020;</xref></sup></td>
<td valign="middle" align="center">151 (56.1)</td>
<td valign="middle" align="center">289 (57.9)</td>
<td valign="middle" align="center">0.634</td>
</tr>
<tr>
<td valign="middle" align="left">Previous wheezing episode<sup><xref ref-type="table-fn" rid="table2-fn4-aard-6-47">&#x2020;</xref></sup></td>
<td valign="middle" align="center">25 (9.3)</td>
<td valign="middle" align="center">83 (16.6)</td>
<td valign="middle" align="center">0.005</td>
</tr>
<tr>
<td valign="middle" align="left">Allergic disease family history<sup><xref ref-type="table-fn" rid="table2-fn4-aard-6-47">&#x2020;</xref></sup></td>
<td valign="middle" align="center">2 (0.7)</td>
<td valign="middle" align="center">8 (1.6)</td>
<td valign="middle" align="center">0.316</td>
</tr>
<tr>
<td valign="middle" align="left">Previous admission history<sup><xref ref-type="table-fn" rid="table2-fn4-aard-6-47">&#x2020;</xref></sup></td>
<td valign="middle" align="center">53 (19.7)</td>
<td valign="middle" align="center">145 (29.1)</td>
<td valign="middle" align="center">0.005</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="table2-fn1-aard-6-47"><p>Values are presented as mean or number (%). CRP: normal range, 0&#x2013;0.5 mg/dL; lymphocyte: normal range, 20%&#x2013;50%.</p></fn>
<fn id="table2-fn2-aard-6-47"><p>ICU, intensive care unit; CRP, C-reactive protein.</p></fn>
<fn id="table2-fn3-aard-6-47"><label>&#x2217;</label><p>Student <italic>t</italic>-test.</p></fn>
<fn id="table2-fn4-aard-6-47"><label>&#x2020;</label><p>Chi-square test.</p></fn>
</table-wrap-foot>
</table-wrap>
<table-wrap id="T3-aard-6-47" position="float">
<label>Table 3.</label>
<caption xml:lang="en"><p>The ratio of single infection to coinfection of respiratory viruses isolated for 768 hospitalized children with acute bronchiolitis</p></caption>
<table frame="hsides" rules="all">
<thead>
<tr>
<th valign="middle" align="left">Variable</th>
<th valign="middle" align="center">Total (n)</th>
<th valign="middle" align="center">Single infection, n (%)</th>
<th valign="middle" align="center">Coinfection, n (%)</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="middle" align="left">Adenovirus</td>
<td valign="middle" align="center">139</td>
<td valign="middle" align="center">16 (10.5)</td>
<td valign="middle" align="center">123 (88.5)</td>
</tr>
<tr>
<td valign="middle" align="left">Influenza A virus</td>
<td valign="middle" align="center">16</td>
<td valign="middle" align="center">6 (37.5)</td>
<td valign="middle" align="center">10 (62.5)</td>
</tr>
<tr>
<td valign="middle" align="left">Influenza B virus</td>
<td valign="middle" align="center">9</td>
<td valign="middle" align="center">3 (33.3)</td>
<td valign="middle" align="center">6 (66.7)</td>
</tr>
<tr>
<td valign="middle" align="left">Metapneumovirus</td>
<td valign="middle" align="center">40</td>
<td valign="middle" align="center">13 (32.5)</td>
<td valign="middle" align="center">27 (67.5)</td>
</tr>
<tr>
<td valign="middle" align="left">Respiratory syncytial virus A</td>
<td valign="middle" align="center">252</td>
<td valign="middle" align="center">95 (37.7)</td>
<td valign="middle" align="center">157 (62.3)</td>
</tr>
<tr>
<td valign="middle" align="left">Respiratory syncytial virus B</td>
<td valign="middle" align="center">140</td>
<td valign="middle" align="center">57 (40.7)</td>
<td valign="middle" align="center">83 (59.3)</td>
</tr>
<tr>
<td valign="middle" align="left">Parainfluenza 1</td>
<td valign="middle" align="center">35</td>
<td valign="middle" align="center">10 (28.6)</td>
<td valign="middle" align="center">25 (71.4)</td>
</tr>
<tr>
<td valign="middle" align="left">Parainfluenza 2</td>
<td valign="middle" align="center">10</td>
<td valign="middle" align="center">3 (30.4)</td>
<td valign="middle" align="center">7 (70.0)</td>
</tr>
<tr>
<td valign="middle" align="left">Parainfluenza 3</td>
<td valign="middle" align="center">33</td>
<td valign="middle" align="center">7 (21.2)</td>
<td valign="middle" align="center">26 (78.8)</td>
</tr>
<tr>
<td valign="middle" align="left">Parainfluenza 4</td>
<td valign="middle" align="center">27</td>
<td valign="middle" align="center">9 (33.3)</td>
<td valign="middle" align="center">18 (66.7)</td>
</tr>
<tr>
<td valign="middle" align="left">Human rhinovirus</td>
<td valign="middle" align="center">257</td>
<td valign="middle" align="center">53 (20.6)</td>
<td valign="middle" align="center">204 (79.4)</td>
</tr>
<tr>
<td valign="middle" align="left">Corona 229E virus</td>
<td valign="middle" align="center">8</td>
<td valign="middle" align="center">0 (0)</td>
<td valign="middle" align="center">8 (100)</td>
</tr>
<tr>
<td valign="middle" align="left">Corona NL63 virus</td>
<td valign="middle" align="center">11</td>
<td valign="middle" align="center">3 (27.3)</td>
<td valign="middle" align="center">8 (72.3)</td>
</tr>
<tr>
<td valign="middle" align="left">Corona OC43 virus</td>
<td valign="middle" align="center">22</td>
<td valign="middle" align="center">2 (9.1)</td>
<td valign="middle" align="center">20 (90.9)</td>
</tr>
<tr>
<td valign="middle" align="left">Enterovirus</td>
<td valign="middle" align="center">60</td>
<td valign="middle" align="center">2 (3.3)</td>
<td valign="middle" align="center">58 (96.7)</td>
</tr>
<tr>
<td valign="middle" align="left">Human bocavirus</td>
<td valign="middle" align="center">96</td>
<td valign="middle" align="center">12 (12.5)</td>
<td valign="middle" align="center">84 (87.5)</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap id="T4-aard-6-47" position="float">
<label>Table 4.</label>
<caption xml:lang="en"><p>Correlation of severity with coinfected viruses for 768 hospitalized children with acute bronchiolitis<xref ref-type="table-fn" rid="table4-fn2-aard-6-47">&#x2217;</xref></p></caption>
<table frame="hsides" rules="all">
<thead>
<tr>
<th valign="middle" align="left" rowspan="2">Infection</th>
<th valign="middle" align="center" colspan="7">Coinfected viruses<hr/></th>
</tr>
<tr>
<th valign="middle" align="center">ADV (n=139)</th>
<th valign="middle" align="center">hMPV (n=96)</th>
<th valign="middle" align="center">RSV A (n=252)</th>
<th valign="middle" align="center">RSV B (n=140)</th>
<th valign="middle" align="center">hRV (n=257)</th>
<th valign="middle" align="center">ETV (n=60)</th>
<th valign="middle" align="center">hBoV (n=96)</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="middle" align="left">ADV</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">0.239 (0.137)</td>
<td valign="middle" align="center">&#x2013;0.133 (0.034)<sup><xref ref-type="table-fn" rid="table4-fn3-aard-6-47">&#x2020;</xref></sup></td>
<td valign="middle" align="center">0.046 (0.589)</td>
<td valign="middle" align="center">&#x2013;0.002 (0.975)</td>
<td valign="middle" align="center">0.092 (0.484)</td>
<td valign="middle" align="center">0.012 (0.907)</td>
</tr>
<tr>
<td valign="middle" align="left">Flu A</td>
<td valign="middle" align="center">0.103 (0.226)</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">0.106 (0.094)</td>
<td valign="middle" align="center">0.053 (0.532)</td>
<td valign="middle" align="center">0.117 (0.061)</td>
<td valign="middle" align="center">0.066 (0.614)</td>
<td valign="middle" align="center">0.134 (0.195)</td>
</tr>
<tr>
<td valign="middle" align="left">Flu B</td>
<td valign="middle" align="center">&#x2013;0.100 (0.239)</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">&#x2013;0.074 (0.245)</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">&#x2013;0.085 (0.175)</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">&#x2013;0.106 (0.306)</td>
</tr>
<tr>
<td valign="middle" align="left">hMPV</td>
<td valign="middle" align="center">&#x2013;0.004 (0.960)</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">0.005 (0.940)</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">&#x2013;0.081 (0.194)</td>
<td valign="middle" align="center">0.053 (0.688)</td>
<td valign="middle" align="center">0.092 (0.373)</td>
</tr>
<tr>
<td valign="middle" align="left">RSV A</td>
<td valign="middle" align="center">&#x2013;0.051 (0.550)</td>
<td valign="middle" align="center">0.106 (0.516)</td>
<td valign="middle" align="center">&#x00A0;</td>
<td valign="middle" align="center">&#x2013;0.057 (0.500)</td>
<td valign="middle" align="center">&#x2013;0.042 (0.503)</td>
<td valign="middle" align="center">0.073 (0.577)</td>
<td valign="middle" align="center">&#x2013;0.027 (0.794)</td>
</tr>
<tr>
<td valign="middle" align="left">RSV B</td>
<td valign="middle" align="center">0.115 (0.176)</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">&#x2013;0.050 (0.432)</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">0.077 (0.216)</td>
<td valign="middle" align="center">&#x2013;0.066 (0.615)</td>
<td valign="middle" align="center">&#x2013;0.069 (0.507)</td>
</tr>
<tr>
<td valign="middle" align="left">hRV</td>
<td valign="middle" align="center">0.015 (0.863)</td>
<td valign="middle" align="center">0.189 (0.242)</td>
<td valign="middle" align="center">&#x2013;0.131 (0.038)<sup><xref ref-type="table-fn" rid="table4-fn3-aard-6-47">&#x2020;</xref></sup></td>
<td valign="middle" align="center">0.011 (0.897)</td>
<td valign="middle" align="center">&#x00A0;</td>
<td valign="middle" align="center">0.195 (0.135)</td>
<td valign="middle" align="center">0.190 (0.064)</td>
</tr>
<tr>
<td valign="middle" align="left">PIV 1</td>
<td valign="middle" align="center">&#x2013;0.098 (0.252)</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">&#x2013;0.082 (0.197)</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">0.055 (0.378)</td>
<td valign="middle" align="center">0.099 (0.452)</td>
<td valign="middle" align="center">0.085 (0.411)</td>
</tr>
<tr>
<td valign="middle" align="left">PIV 2</td>
<td valign="middle" align="center">0.127 (0.136)</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">&#x2013;0.023 (0.718)</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">0.093 (0.136)</td>
<td valign="middle" align="center">0.172 (0.189)</td>
<td valign="middle" align="center">0.160 (0.118)</td>
</tr>
<tr>
<td valign="middle" align="left">PIV 3</td>
<td valign="middle" align="center">&#x2013;0.070 (0.415)</td>
<td valign="middle" align="center">0.280 (0.080)</td>
<td valign="middle" align="center">&#x2013;0.023 (0.718)</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">0.146 (0.019)<sup><xref ref-type="table-fn" rid="table4-fn4-aard-6-47">&#x2021;</xref></sup></td>
<td valign="middle" align="center">0.152 (0.246)</td>
<td valign="middle" align="center">0.053 (0.609)</td>
</tr>
<tr>
<td valign="middle" align="left">PIV 4</td>
<td valign="middle" align="center">&#x2013;0.057 (0.512)</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">0.015 (0.840)</td>
<td valign="middle" align="center">0.068 (0.481)</td>
<td valign="middle" align="center">0.016 (0.809)</td>
<td valign="middle" align="center">&#x2013;0.029 (0.826)</td>
<td valign="middle" align="center">&#x2013;0.114 (0.268)</td>
</tr>
<tr>
<td valign="middle" align="left">ETV</td>
<td valign="middle" align="center">0.132 (0.124)</td>
<td valign="middle" align="center">0.271 (0.115)</td>
<td valign="middle" align="center">0.121 (0.106)</td>
<td valign="middle" align="center">&#x2013;0.010 (0.920)</td>
<td valign="middle" align="center">0.164 (0.013)<sup><xref ref-type="table-fn" rid="table4-fn4-aard-6-47">&#x2021;</xref></sup></td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">0.170 (0.097)</td>
</tr>
<tr>
<td valign="middle" align="left">hCoV 229E</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">&#x2013;0.031 (0.627)</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">&#x2013;0.031 (0.624)</td>
<td valign="middle" align="center">&#x2013;0.149 (0.257)</td>
<td valign="middle" align="center">-</td>
</tr>
<tr>
<td valign="middle" align="left">hCoV NL63</td>
<td valign="middle" align="center">&#x2013;0.144 (0.093)</td>
<td valign="middle" align="center">&#x2013;0.136 (0.437)</td>
<td valign="middle" align="center">&#x2013;0.152 (0.042)<sup><xref ref-type="table-fn" rid="table4-fn3-aard-6-47">&#x2020;</xref></sup></td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">&#x2013;0.002 (0.981)</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">-</td>
</tr>
<tr>
<td valign="middle" align="left">hCoV OC43</td>
<td valign="middle" align="center">&#x2013;0.047 (0.587)</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">&#x2013;0.024 (0.700)</td>
<td valign="middle" align="center">&#x2013;0.039 (0.651)</td>
<td valign="middle" align="center">0.062 (0.322)</td>
<td valign="middle" align="center">-</td>
<td valign="middle" align="center">&#x2013;0.106 (0.306)</td>
</tr>
<tr>
<td valign="middle" align="left">hBoV</td>
<td valign="middle" align="center">&#x2013;0.073 (0.397)</td>
<td valign="middle" align="center">0.351 (0.038)<sup><xref ref-type="table-fn" rid="table4-fn4-aard-6-47">&#x2021;</xref></sup></td>
<td valign="middle" align="center">&#x2013;0.034 (0.651)</td>
<td valign="middle" align="center">0.078 (0.418)</td>
<td valign="middle" align="center">0.063 (0.344)</td>
<td valign="middle" align="center">0.035 (0.792)</td>
<td valign="middle" align="center">-</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="table4-fn1-aard-6-47"><p>ADV, adenovirus; hMPV, human metapneumovirus; RSV, respiratory syncytial virus; hRV, human rhinovirus; ETV, enterovirus; hBoV, human bocavirus; Flu, influenza virus; PIV, parainfluenza virus; hCoV, human coronavirus.</p></fn>
<fn id="table4-fn2-aard-6-47"><label>&#x2217;</label><p>Spearman correlation analysis and then chi-square test.</p></fn>
<fn id="table4-fn3-aard-6-47"><label>&#x2020;</label><p>Negative correlation (reduced severity).</p></fn>
<fn id="table4-fn4-aard-6-47"><label>&#x2021;</label><p>Positive correlation (elevated severity).</p></fn>
</table-wrap-foot>
</table-wrap>
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