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<?covid-19-tdm?>
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="brief-report">
<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Pediatr.</journal-id>
<journal-title>Frontiers in Pediatrics</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Pediatr.</abbrev-journal-title>
<issn pub-type="epub">2296-2360</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fped.2021.700656</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Pediatrics</subject>
<subj-group>
<subject>Brief Research Report</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>National Trends in Disease Activity for COVID-19 Among Children in the US</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Hutch</surname> <given-names>Meghan R.</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/1362469/overview"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Liu</surname> <given-names>Molei</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Avillach</surname> <given-names>Paul</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<xref ref-type="aff" rid="aff4"><sup>4</sup></xref>
<xref ref-type="aff" rid="aff5"><sup>5</sup></xref>
</contrib>
<contrib contrib-type="author" id="collab1">
<collab>Consortium for Clinical Characterization of COVID-19 by EHR (4CE)</collab>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name><surname>Luo</surname> <given-names>Yuan</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="corresp" rid="c002"><sup>&#x0002A;</sup></xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name><surname>Bourgeois</surname> <given-names>Florence T.</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<xref ref-type="aff" rid="aff5"><sup>5</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x0002A;</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/1299996/overview"/>
</contrib>
</contrib-group>
<aff id="aff1"><sup>1</sup><institution>Department of Preventive Medicine, Northwestern University</institution>, <addr-line>Chicago, IL</addr-line>, <country>United States</country></aff>
<aff id="aff2"><sup>2</sup><institution>Department of Biostatistics, Harvard T.H. Chan School of Public Health</institution>, <addr-line>Boston, MA</addr-line>, <country>United States</country></aff>
<aff id="aff3"><sup>3</sup><institution>Department of Pediatrics, Harvard Medical School</institution>, <addr-line>Boston, MA</addr-line>, <country>United States</country></aff>
<aff id="aff4"><sup>4</sup><institution>Department of Biomedical Informatics, Harvard Medical School</institution>, <addr-line>Boston, MA</addr-line>, <country>United States</country></aff>
<aff id="aff5"><sup>5</sup><institution>Computational Health Informatics Program (CHIP), Boston Children&#x00027;s Hospital</institution>, <addr-line>Boston, MA</addr-line>, <country>United States</country></aff>
<author-notes>
<fn fn-type="edited-by"><p>Edited by: Kinsuk Chauhan, Icahn School of Medicine at Mount Sinai, United States</p></fn>
<fn fn-type="edited-by"><p>Reviewed by: Lokesh Tiwari, All India Institute of Medical Sciences (Patna), India; Amrita Dosanjh, University of California, San Diego, United States</p></fn>
<corresp id="c001">&#x0002A;Correspondence: Florence T. Bourgeois <email>florence.bourgeois&#x00040;childrens.harvard.edu</email></corresp>
<corresp id="c002">Yuan Luo <email>yuan.luo&#x00040;northwestern.edu</email></corresp>
<fn fn-type="other" id="fn001"><p>This article was submitted to Children and Health, a section of the journal Frontiers in Pediatrics</p></fn></author-notes>
<pub-date pub-type="epub">
<day>08</day>
<month>07</month>
<year>2021</year>
</pub-date>
<pub-date pub-type="collection">
<year>2021</year>
</pub-date>
<volume>9</volume>
<elocation-id>700656</elocation-id>
<history>
<date date-type="received">
<day>26</day>
<month>04</month>
<year>2021</year>
</date>
<date date-type="accepted">
<day>04</day>
<month>06</month>
<year>2021</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x000A9; 2021 Hutch, Liu, Avillach, Consortium for Clinical Characterization of COVID-19 by EHR (4CE), Luo and Bourgeois.</copyright-statement>
<copyright-year>2021</copyright-year>
<copyright-holder>Hutch, Liu, Avillach, Consortium for Clinical Characterization of COVID-19 by EHR (4CE), Luo and Bourgeois</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>
<abstract><p>Ongoing monitoring of COVID-19 disease burden in children will help inform mitigation strategies and guide pediatric vaccination programs. Leveraging a national, comprehensive dataset, we sought to quantify and compare disease burden and trends in hospitalizations for children and adults in the US.</p></abstract>
<kwd-group>
<kwd>COVID-19</kwd>
<kwd>surveillance</kwd>
<kwd>public health</kwd>
<kwd>hospitalization</kwd>
<kwd>pediatric</kwd>
</kwd-group>
<counts>
<fig-count count="2"/>
<table-count count="0"/>
<equation-count count="0"/>
<ref-count count="8"/>
<page-count count="4"/>
<word-count count="2270"/>
</counts>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="s1">
<title>Introduction</title>
<p>Data on coronavirus disease 2019 (COVID-19) in children and adolescents remain limited, even though 3.6 million pediatric cases have been reported in the US to date and several disease manifestations unique to children have been identified (<xref ref-type="bibr" rid="B1">1</xref>, <xref ref-type="bibr" rid="B2">2</xref>). Understanding the epidemiology of pediatric infections and quantifying the disease burden in children is necessary to inform mitigation strategies, support therapeutic development, and guide pediatric vaccination programs (<xref ref-type="bibr" rid="B3">3</xref>).</p>
<p>Several vaccines are currently under study in clinical trials in adolescents and children, with one vaccine approved by the FDA in March 2021 for use in children as young as 12 years. In addition to providing direct health benefits, an important public health goal of immunizing children is achieving herd immunity and removing children as vectors of transmission to vulnerable older adults. Analyses of disease activity across the US will help identify regions where additional pediatric vaccination efforts are needed and enable measurement of the direct and indirect benefits of pediatric vaccination strategies.</p>
<p>In July of 2020, the US Department of Health and Human Services began collecting data on hospitalizations related to COVID-19 for both pediatric and adult patients. Leveraging this comprehensive national datasource, we sought to assess the value of these data to quantify and compare disease burden and trends in hospitalizations for children and adults in the US.</p>
</sec>
<sec sec-type="methods" id="s2">
<title>Methods</title>
<p>We evaluated COVID-19 hospitalizations reported to the US Department of Health and Human Services (<xref ref-type="bibr" rid="B4">4</xref>). These data are collected under a federal mandate requiring hospitals to provide utilization and capacity data in order to support the public health response to COVID-19 (<xref ref-type="bibr" rid="B5">5</xref>). Data cover all hospitals in the 50 States registered with Centers for Medicare and Medicaid Services, and include daily aggregated counts of new adult and pediatric hospitalizations with laboratory-confirmed COVID-19 at the time of admission. We analyzed all data collected since reporting started July 31, 2020 through April 15, 2021. Counts were aggregated weekly from Friday to Thursday.</p>
<p>We used US Census population estimates to calculate weekly hospitalizations per 100,000 children (0&#x02013;17 years) and adults, nationally and by region (<xref ref-type="bibr" rid="B6">6</xref>). Regions were defined according to US Census classification. To quantify and compare the temporality of disease activity between adult and pediatric populations, we conducted univariate change point analyses on national and regional hospitalization rates for children and adults and identified the date with the largest likelihood of representing an upward change in mean hospitalization rates (<xref ref-type="bibr" rid="B7">7</xref>). Descriptive and statistical analyses were performed using R version 3.6.0 (R Foundation; <ext-link ext-link-type="uri" xlink:href="https://github.com/meghutch/COVID-19-Hospitalization-Trends">https://github.com/meghutch/COVID-19-Hospitalization-Trends</ext-link>). <italic>P</italic>-values were estimated with parametric bootstrapping and deemed significant when adjusted for Bonferroni correction (<italic>P</italic> &#x0003C; 0.005). Significant <italic>p</italic>-values reflect the likelihood of a change point existing within the time interval.</p>
</sec>
<sec sec-type="results" id="s3">
<title>Results</title>
<p>Over the 37-week study period, there were 35,919 pediatric and 2,052,932 adult COVID-19 hospitalizations, corresponding to a weekly median of 906 (IQR 717&#x02013;1,249) pediatric and 38,675 (IQR 32,338&#x02013;84,331) adult hospitalizations. National weekly hospitalization rates were 1.2 (IQR 1&#x02013;1.7) per 100,000 children and 15.1 (IQR 12.6&#x02013;32.9) per 100,000 adults (<xref ref-type="fig" rid="F1">Figure 1</xref>). Change point analyses identified a significant increase in mean hospitalization rate the week of October 23 for both pediatric and adult populations (<italic>P</italic> = 0.0001 and <italic>P</italic> = 0.0004, respectively). Adult hospitalizations peaked during the week of January 1, at a rate of 44.3 per 100,000 adults, while pediatric hospitalizations peaked the following week, at a rate of 2.1 per 100,000 children.</p>
<fig id="F1" position="float">
<label>Figure 1</label>
<caption><p>National COVID-19 Hospitalizations among Children and Adults. Hospitalizations were standardized per 100,000 children or adults using US Census population estimates. The scale for pediatric hospitalizations is 10-fold less than for adults. Asterisks indicate significant (<italic>P</italic> &#x0003C; 0.005) change points.</p></caption>
<graphic xlink:href="fped-09-700656-g0001.tif"/>
</fig>
<p>Hospitalization rates and timing of change points varied by region (<xref ref-type="fig" rid="F2">Figure 2</xref>). Median weekly hospitalization rates were highest in the South for both children (1.5 per 100,000 children) and adults (20.2 per 100,000 adults), and lowest for both children and adults in the West (0.9 per 100,000 children and 11.6 per 100,000 adults). The earliest change point for both pediatric and adult hospitalizations occurred in the Midwest the weeks of September 25 (<italic>P</italic> = 0.0002) and October 2 (<italic>P</italic> = 0.0041), respectively. Across the other regions, significant change points were detected during the weeks of October 23 and October 30 for both pediatric and adult hospitalizations. Among children, the earliest peak occurred in the Midwest the week of November 6, while hospitalizations continued to rise in the Northeast until early February.</p>
<fig id="F2" position="float">
<label>Figure 2</label>
<caption><p>COVID-19 Hospitalization Trends by Region. Hospitalizations were standardized per 100,000 children or adults using US Census population estimates. The scale for pediatric hospitalizations is 10-fold less than for adults. Asterisks indicate significant (<italic>P</italic> &#x0003C; 0.005) change points.</p></caption>
<graphic xlink:href="fped-09-700656-g0002.tif"/>
</fig>
</sec>
<sec sec-type="discussion" id="s4">
<title>Discussion</title>
<p>These national data indicate that peaks in COVID-19 hospitalization rates were 20-fold less for children than adults, though temporal trends were generally similar for pediatric and adult hospitalizations. There was substantial variation across regions, both in rates of hospitalizations observed and timing of changes in disease activity. Our findings highlight the importance of dedicated analyses of pediatric COVID-19 data to measure the impact of the pandemic on children, assess public health measures, and anticipate pediatric healthcare resource needs. Our study builds on prior work by Levin et al. by evaluating a comprehensive data source covering all 50 states and providing a direct comparison of pediatric and adult hospitalization rates through the launch of vaccination programs (<xref ref-type="bibr" rid="B8">8</xref>).</p>
<p>Limitations of our study include use of an observational dataset subject to potential misclassification and under-reporting. We also were not able to perform additional patient-level or age group specific analyses as the dataset only identifies patients as pediatric and does not provide detailed demographic or other clinical information.</p>
<p>COVID-19-related hospitalizations are a more robust measure of disease activity than COVID-19 case counts, as they are not subject to biases in testing strategies and represent a relevant health outcome. Evaluation of pediatric and adult hospitalization rates may inform policies for return to work and school activities as adults and children are vaccinated, as well as guide targeted protection of specific population groups. For any policy, the large variations in regional hospitalization rates underscore the need to consider local disease activity in implementation and assessment of mitigation strategies.</p>
</sec>
<sec sec-type="data-availability-statement" id="s5">
<title>Data Availability Statement</title>
<p>Publicly available datasets were analyzed in this study. These data can be found at: <ext-link ext-link-type="uri" xlink:href="https://healthdata.gov/Hospital/COVID-19-Reported-Patient-Impact-and-Hospital-Capa/g62h-syeh">https://healthdata.gov/Hospital/COVID-19-Reported-Patient-Impact-and-Hospital-Capa/g62h-syeh</ext-link>.</p>
</sec>
<sec id="s6">
<title>Author Contributions</title>
<p>MH conceptualized and designed the study, collected data, performed the analyses, drafted the initial manuscript, and revised the manuscript. ML performed data analysis and revised the manuscript. PA critically reviewed the manuscript for important intellectual content and revised the manuscript. YL coordinated and supervised data collection, critically reviewed the manuscript for important intellectual content, and revised the manuscript. FB conceptualized and designed the study, coordinated and supervised data collection, critically reviewed the manuscript for important intellectual content, and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.</p>
</sec>
<sec id="s7">
<title>The Consortium for Clinical Characterization of COVID-19 by EHR (4CE) Members</title>
<p>James R Aaron, Giuseppe Agapito, Adem Albayrak, Mario Alessiani, Danilo F Amendola, Li L. L. J Anthony, Bruce J Aronow, Fatima Ashraf, Andrew Atz, Paul Avillach, James Balshi, Brett K Beaulieu-Jones, Douglas S Bell, Antonio Bellasi, Riccardo Bellazzi, Vincent Benoit, Michele Beraghi, Jos&#x000E9; Luis Bernal Sobrino, M&#x000E9;lodie Bernaux, Romain Bey, Alvar Blanco Mart&#x000ED;nez, Martin Boeker, Clara-Lea Bonzel, John Booth, Silvano Bosari, Florence T Bourgeois, Robert L Bradford, Gabriel A Brat, St&#x000E9;phane Br&#x000E9;ant, Nicholas W Brown, William A Bryant, Mauro Bucalo, Anita Burgun, Tianxi Cai, Mario Cannataro, Aldo Carmona, Charlotte Caucheteux, Julien Champ, Jin Chen, Krista Chen, Luca Chiovato, Lorenzo Chiudinelli, Kelly Cho, James J Cimino, Tiago K Colicchio, Sylvie Cormont, S&#x000E9;bastien Cossin, Jean B Craig, Juan Luis Cruz Berm&#x000FA;dez, Jaime Cruz Rojo, Arianna Dagliati, Mohamad Daniar, Christel Daniel, Priyam Das, Anahita Davoudi, Batsal Devkota, Julien Dubiel, Loic Esteve, Hossein Estiri, Shirley Fan, Robert W Follett, Paula S. A Gaiolla, Thomas Ganslandt, Noelia Garc&#x000ED;a Barrio, Lana X Garmire, Nils Gehlenborg, Alon Geva, Tobias Gradinger, Alexandre Gramfort, Romain Griffier, Nicolas Griffon, Olivier Grisel, Alba Guti&#x000E9;rrez-Sacrist&#x000E1;n, David A Hanauer, Christian Haverkamp, Bing He, Darren W Henderson, Martin Hilka, Yuk-Lam Ho, John H Holmes, Chuan Hong, Petar Horki, Kenneth M Huling, Meghan R Hutch, Richard W Issitt, Anne Sophie Jannot, Vianney Jouhet, Mark S Keller, Katie Kirchoff, Jeffrey G Klann, Isaac S Kohane, Ian D Krantz, Detlef Kraska, Ashok K Krishnamurthy, Sehi L&#x00027;Yi, Trang T Le, Judith Leblanc, Andressa RR Leite, Guillaume Lemaitre, Leslie Lenert, Damien Leprovost, Molei Liu, Ne Hooi Will Loh, Sara Lozano-Zahonero, Yuan Luo, Kristine E Lynch, Sadiqa Mahmood, Sarah Maidlow, Adeline Makoudjou, Alberto Malovini, Kenneth D Mandl, Chengsheng Mao, Anupama Maram, Patricia Martel, Aaron J Masino, Maria Mazzitelli, Arthur Mensch, Marianna Milano, Marcos F Minicucci, Bertrand Moal, Jason H Moore, Cinta Moraleda, Jeffrey S Morris, Michele Morris, Karyn L Moshal, Sajad Mousavi, Danielle L Mowery, Douglas A Murad, Shawn N Murphy, Thomas P Naughton, Antoine Neuraz, Kee Yuan Ngiam, Wanjiku FM Njoroge, James B Norman, Jihad Obeid, Marina P Okoshi, Karen L Olson, Gilbert S Omenn, Nina Orlova, Brian D Ostasiewski, Nathan P Palmer, Nicolas Paris, Lav P Patel, Miguel Pedrera Jimenez, Emily R Pfaff, Danielle Pillion, Hans U Prokosch, Robson A Prudente, V&#x000ED;ctor Quir&#x000F3;s Gonz&#x000E1;lez, Rachel B Ramoni, Maryna Raskin, Siegbert Rieg, Gustavo Roig Dom&#x000ED;nguez, Pablo Rojo, Carlos S&#x000E1;ez, Elisa Salamanca, Malarkodi J Samayamuthu, L. Nelson Sanchez-Pinto, Arnaud Sandrin, Janaina CC Santos, Maria Savino, Emily R Schriver, Petra Schubert, Juergen Schuettler, Luigia Scudeller, Neil J Sebire, Pablo Serrano Balazote, Patricia Serre, Arnaud Serret-Larmande, Zahra Shakeri, Domenick Silvio, Piotr Sliz, Jiyeon Son, Charles Sonday, Andrew M South, Anastasia Spiridou, Amelia LM Tan, Bryce WQ Tan, Byorn WL Tan, Suzana E Tanni, Deanne M Taylor, Ana I Terriza Torres, Valentina Tibollo, Patric Tippmann, Carlo Torti, Enrico M Trecarichi, Yi-Ju Tseng, Andrew K Vallejos, Gael Varoquaux, Margaret E Vella, Guillaume Verdy, Jill-J&#x000EA;nn Vie, Shyam Visweswaran, Michele Vitacca, Kavishwar B Wagholikar, Lemuel R Waitman, Xuan Wang, Demian Wassermann, Griffin M Weber, Zongqi Xia, Nadir Yehya, William Yuan, Alberto Zambelli, Harrison G Zhang, Daniel Zoeller, Chiara Zucco.</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>
</body>
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<glossary>
<def-list>
<title>Abbreviations</title>
<def-item><term>COVID-19</term>
<def><p>Coronavirus disease 2019.</p></def></def-item>
</def-list>
</glossary> 
</back>
</article>