What are international trends in hospitalizations for children and youth with SARS-CoV-2, and what are the epidemiological and clinical features of these patients?
This cohort study of 671 children and youth found discrete surges in hospitalizations with variable trends and timing across countries. Common complications included cardiac arrhythmias and viral pneumonia, and laboratory findings included elevations in markers of inflammation and abnormalities of coagulation; few children and youth were treated with medications directed specifically at SARS-CoV-2.
These findings suggest large-scale informatics-based approaches used to incorporate electronic health record data across health care systems can provide an efficient source of information to monitor disease activity and define epidemiological and clinical features of pediatric patients hospitalized with SARS-CoV-2 infections.
Additional sources of pediatric epidemiological and clinical data are needed to efficiently study COVID-19 in children and youth and inform infection prevention and clinical treatment of pediatric patients.
To describe international hospitalization trends and key epidemiological and clinical features of children and youth with COVID-19.
Design, Setting, and Participants
This retrospective cohort study included pediatric patients hospitalized between February 2 and October 10, 2020. Patient-level electronic health record (EHR) data were collected across 27 hospitals in France, Germany, Spain, Singapore, the UK, and the US. Patients younger than 21 years who tested positive for COVID-19 and were hospitalized at an institution participating in the Consortium for Clinical Characterization of COVID-19 by EHR were included in the study.
Main Outcomes and Measures
Patient characteristics, clinical features, and medication use.
There were 347 males (52%; 95% CI, 48.5-55.3) and 324 females (48%; 95% CI, 44.4-51.3) in this study’s cohort. There was a bimodal age distribution, with the greatest proportion of patients in the 0- to 2-year (199 patients [30%]) and 12- to 17-year (170 patients [25%]) age range. Trends in hospitalizations for 671 children and youth found discrete surges with variable timing across 6 countries. Data from this cohort mirrored national-level pediatric hospitalization trends for most countries with available data, with peaks in hospitalizations during the initial spring surge occurring within 23 days in the national-level and 4CE data. A total of 27 364 laboratory values for 16 laboratory tests were analyzed, with mean values indicating elevations in markers of inflammation (C-reactive protein, 83 mg/L; 95% CI, 53-112 mg/L; ferritin, 417 ng/mL; 95% CI, 228-607 ng/mL; and procalcitonin, 1.45 ng/mL; 95% CI, 0.13-2.77 ng/mL). Abnormalities in coagulation were also evident (D-dimer, 0.78 ug/mL; 95% CI, 0.35-1.21 ug/mL; and fibrinogen, 477 mg/dL; 95% CI, 385-569 mg/dL). Cardiac troponin, when checked (n = 59), was elevated (0.032 ng/mL; 95% CI, 0.000-0.080 ng/mL). Common complications included cardiac arrhythmias (15.0%; 95% CI, 8.1%-21.7%), viral pneumonia (13.3%; 95% CI, 6.5%-20.1%), and respiratory failure (10.5%; 95% CI, 5.8%-15.3%). Few children were treated with COVID-19–directed medications.
Conclusions and Relevance
This study of EHRs of children and youth hospitalized for COVID-19 in 6 countries demonstrated variability in hospitalization trends across countries and identified common complications and laboratory abnormalities in children and youth with COVID-19 infection. Large-scale informatics-based approaches to integrate and analyze data across health care systems complement methods of disease surveillance and advance understanding of epidemiological and clinical features associated with COVID-19 in children and youth.
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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.
Accepted for Publication: March 23, 2021.
Published: June 11, 2021. doi:10.1001/jamanetworkopen.2021.12596
Correction: This article was corrected on July 23, 2021, to fix errors in the byline.
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2021 Bourgeois FT et al. JAMA Network Open.
Corresponding Authors: Paul Avillach, MD, PhD, Department of Biomedical Informatics, Harvard Medical School, 10 Shattuck St, Boston, MA 02115 (firstname.lastname@example.org); Florence Bourgeois, MD, MPH, Boston Children’s Hospital, 300 Longwood Ave, Boston, MA 02115 (email@example.com).
Author Contributions: Drs Bourgeois and Avillach had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Bourgeois, Gutiérrez-Sacristán, Hong, Aronow, Gehlenborg, Geva, Mandl, Moshal, Murphy, Omenn, Serrano Balazote, South, Weber, Kohane, Cai, Avillach.
Acquisition, analysis, or interpretation of data: Bourgeois, Gutiérrez-Sacristán, Keller, Hong, Liu, Bonzel, Tan, Aronow, Boeker, Booth, Cruz Rojo, Devkota, García Barrio, Geva, Hanauer, Hutch, Issitt, Klann, Luo, Mao, Moal, Moshal, Neuraz, Ngiam, Omenn, Patel, Pedrera-Jiménez, Sebire, Serret-Larmande, South, Spiridou, Taylor, Tippmann, Visweswaran, Weber, Kohane, Cai, Avillach.
Drafting of the manuscript: Bourgeois, Gutiérrez-Sacristán, Keller, Hong, Liu, Bonzel, Geva, Hutch, Issitt, Moshal, Murphy, Spiridou, Cai, Avillach.
Critical revision of the manuscript for important intellectual content: Gutiérrez-Sacristán, Hong, Tan, Aronow, Boeker, Booth, Cruz Rojo, Devkota, García Barrio, Gehlenborg, Geva, Hanauer, Issitt, Klann, Luo, Mandl, Mao, Moal, Neuraz, Ngiam, Omenn, Patel, Pedrera-Jiménez, Sebire, Serrano Balazote, Serret-Larmande, South, Spiridou, Taylor, Tippmann, Visweswaran, Weber, Kohane, Cai, Avillach.
Statistical analysis: Gutiérrez-Sacristán, Keller, Hong, Liu, Tan, Devkota, Luo, Serret-Larmande, Cai, Avillach.
Obtained funding: Murphy, Weber, Kohane, Avillach.
Administrative, technical, or material support: Gutiérrez-Sacristán, Bonzel, Tan, Aronow, Boeker, Booth, Cruz Rojo, Devkota, García Barrio, Geva, Hanauer, Hutch, Issitt, Klann, Luo, Mandl, Mao, Murphy, Patel, Pedrera-Jiménez, Sebire, Spiridou, Tippmann, Visweswaran, Weber, Kohane, Avillach.
Supervision: Bourgeois, Aronow, Luo, Murphy, Omenn, Serrano Balazote, South, Spiridou, Kohane, Cai, Avillach.
Conflict of Interest Disclosures: Dr Bourgeois reported being a codirector of the Harvard-MIT Center for Regulatory Science. Mr Keller reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Boeker reported receiving grants from the German Federal Ministry of Education and Research as part of the MIRACUM consortium of the German Medical Informatics Initiative during the conduct of the study. Dr Gehlenborg reported being a cofounder and having equity in Datavisyn during the conduct of the study. Dr Hanauer reported having developed an electronic resource of clinical synonyms that is licensed by the University of Michigan and receiving a portion of the licensing fees for this resource outside the submitted work. Dr Hutch reported receiving grants from the National Institutes of Health T32 Predoctoral Training Program in Biomedical Data Driven Discovery during the conduct of the study. Dr Klann reported receiving grants from the National Institutes of Health during the conduct of the study. Dr South reported receiving grants from the National Institutes of Health during the conduct of the study. Dr Taylor reported receiving personal fees from AstraZeneca outside the submitted work. Dr Kohane reported being on the board of Inovalon. No other disclosures were reported.
Funding/Support: Dr Bourgeois was funded by a grant from the Burroughs Wellcome Fund and supported by the Harvard-MIT Center for Regulatory Science. Mr Keller was funded by grant 5T32HG002295-18 from the National Human Genome Research Institute (NHGRI). Dr Aronow was funded by grant U24 HL148865 from the National Heart, Lung, and Blood Institute (NHLBI). Ms García Barrio was supported by grant PI18/00981 from the Carlos III Health Institute. Dr Gehlenborg was funded by grant T15 LM007092 from the NIH National Library of Medicine. Dr Geva was funded by grant K12 HD047349 from the NIH and Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr Hanauer was funded by grant UL1TR002240 from the National Center for Advancing Translational Sciences (NCATS). Drs Klann and Murphy were funded by grant 5UL1TR001857-05 from the NCATS and grant 5R01HG009174-04 from the NHGRI. Dr Luo was funded by grant R01LM013337 from the NLM. Mr Patel was funded by grant UL1TR002366 from the NCATS. Dr Gutiérrez-Sacristán was funded by grants K23HL148394 and L40HL148910 from the NIH NHLBI and grant UL1TR001420 from the NIH NCATS. Dr Visweswaran was funded by grant R01LM012095 from the NLM and grant UL1TR001857 from the NCATS. Dr Weber was supported by grants UL1TR002541 and UL1TR000005 from the NIH-NCATS, and grant R01LM013345 from the NLM.
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Group Members: The Consortium for Clinical Characterization of COVID-19 by EHR (4CE) Coordinators and Collaborators are listed in Supplement 2.
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