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[Preprint]. 2020 Oct 30:2020.10.29.20222083.

doi: 10.1101/2020.10.29.20222083.

Baseline characteristics, management, and outcomes of 55,270 children and adolescents diagnosed with COVID-19 and 1,952,693 with influenza in France, Germany, Spain, South Korea and the United States: an international network cohort study

Talita Duarte-Salles¹, David Vizcaya², Andrea Pistillo¹, Paula Casajust³, Anthony G Sena^{4

5}, Lana Yin Hui Lai⁶, Albert Prats-Uribe⁷, Waheed-Ul-Rahman Ahmed^{7

8}, Thamir M Alshammari⁹, Heba Alghoul¹⁰, Osaid Alser¹¹, Edward Burn^{1

7}, Seng Chan You¹², Carlos Areia¹³, Clair Blacketer^{4

5}, Scott DuVall^{14

15}, Thomas Falconer¹⁶, Sergio Fernandez-Bertolin¹, Stephen Fortin⁴, Asieh Golozar^{17

18}, Mengchun Gong¹⁹, Eng Hooi Tan⁷, Vojtech Huser²⁰, Pablo Iveli²¹, Daniel R Morales²², Fredrik Nyberg²³, Jose D Posada²⁴, Martina Recalde^{1

25}, Elena Roel¹, Lisa M Schilling²⁶, Nigam H Shah²⁴, Karishma Shah⁷, Marc A Suchard²⁷, Lin Zhang^{28

29}, Ying Zhang¹⁹, Andrew E Williams³⁰, Christian G Reich³¹, George Hripcsak¹⁶, Peter Rijnbeek⁵, Patrick Ryan^{4

16}, Kristin Kostka³¹, Daniel Prieto-Alhambra⁷

Affiliations

¹ Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain.
² Bayer Pharmaceuticals, Sant Joan Despi, Spain.
³ Real-World Evidence, Trial Form Support, Barcelona, Spain.
⁴ Janssen Research & Development, Titusville, NJ, USA.
⁵ Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁶ School of Medical Sciences, University of Manchester, UK.
⁷ Centre for Statistics in Medicine (CSM), Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDROMS), University of Oxford, UK.
⁸ College of Medicine and Health, University of Exeter, St Luke's Campus, Heavitree Road, Exeter, EX1 2LU, UK.
⁹ Medication Safety Research Chair, King Saud University, Saudi Arabia.
¹⁰ Faculty of Medicine, Islamic University of Gaza, Palestine.
¹¹ Massachusetts General Hospital, Harvard Medical School, USA.
¹² Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, South Korea.
¹³ Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK.
¹⁴ Department of Veterans Affairs, Salt Lake City, UT, US.
¹⁵ University of Utah School of Medicine, Salt Lake City, UT, US.
¹⁶ Department of Biomedical Informatics, Columbia University, New York, NY, US.
¹⁷ Regeneron Pharmaceutical, NY USA.
¹⁸ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD USA.
¹⁹ DHC Technologies Co. Ltd. Beijing, China.
²⁰ Lister Hill National Center for Biomedical Communications, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
²¹ Bayer AG, Wuppertal, Germany.
²² Division of Population Health and Genomics, University of Dundee, UK.
²³ School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
²⁴ Department of Medicine, Stanford University, USA.
²⁵ Universitat Autònoma de Barcelona, Spain.
²⁶ Data Science to Patient Value Program, Department of Medicine, University of Colorado Anschutz Medical Campus, US.
²⁷ Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, USA.
²⁸ School of Population Medicine and Public Health, Peking Union Medical College and Chinese Academy of Medical Sciences, China.
²⁹ Melbourne School of Population and Global Health, The University of Melbourne, Australia.
³⁰ Tufts Institute for Clinical Research and Health Policy Studies, US.
³¹ Real World Solutions, IQVIA, Cambridge, MA, USA.

PMID: 33140074
PMCID: PMC7605587
DOI: 10.1101/2020.10.29.20222083

Baseline characteristics, management, and outcomes of 55,270 children and adolescents diagnosed with COVID-19 and 1,952,693 with influenza in France, Germany, Spain, South Korea and the United States: an international network cohort study

Talita Duarte-Salles et al. medRxiv. 2020.

[Preprint]. 2020 Oct 30:2020.10.29.20222083.

doi: 10.1101/2020.10.29.20222083.

Authors

Affiliations

¹ Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain.
² Bayer Pharmaceuticals, Sant Joan Despi, Spain.
³ Real-World Evidence, Trial Form Support, Barcelona, Spain.
⁴ Janssen Research & Development, Titusville, NJ, USA.
⁵ Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
⁶ School of Medical Sciences, University of Manchester, UK.
⁷ Centre for Statistics in Medicine (CSM), Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDROMS), University of Oxford, UK.
⁸ College of Medicine and Health, University of Exeter, St Luke's Campus, Heavitree Road, Exeter, EX1 2LU, UK.
⁹ Medication Safety Research Chair, King Saud University, Saudi Arabia.
¹⁰ Faculty of Medicine, Islamic University of Gaza, Palestine.
¹¹ Massachusetts General Hospital, Harvard Medical School, USA.
¹² Department of Biomedical Informatics, Ajou University School of Medicine, Suwon, South Korea.
¹³ Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, OX3 9DU, UK.
¹⁴ Department of Veterans Affairs, Salt Lake City, UT, US.
¹⁵ University of Utah School of Medicine, Salt Lake City, UT, US.
¹⁶ Department of Biomedical Informatics, Columbia University, New York, NY, US.
¹⁷ Regeneron Pharmaceutical, NY USA.
¹⁸ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, MD USA.
¹⁹ DHC Technologies Co. Ltd. Beijing, China.
²⁰ Lister Hill National Center for Biomedical Communications, National Library of Medicine, National Institutes of Health, Bethesda, MD, USA.
²¹ Bayer AG, Wuppertal, Germany.
²² Division of Population Health and Genomics, University of Dundee, UK.
²³ School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
²⁴ Department of Medicine, Stanford University, USA.
²⁵ Universitat Autònoma de Barcelona, Spain.
²⁶ Data Science to Patient Value Program, Department of Medicine, University of Colorado Anschutz Medical Campus, US.
²⁷ Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, USA.
²⁸ School of Population Medicine and Public Health, Peking Union Medical College and Chinese Academy of Medical Sciences, China.
²⁹ Melbourne School of Population and Global Health, The University of Melbourne, Australia.
³⁰ Tufts Institute for Clinical Research and Health Policy Studies, US.
³¹ Real World Solutions, IQVIA, Cambridge, MA, USA.

PMID: 33140074
PMCID: PMC7605587
DOI: 10.1101/2020.10.29.20222083

Update in

Thirty-Day Outcomes of Children and Adolescents With COVID-19: An International Experience.
Duarte-Salles T, Vizcaya D, Pistillo A, Casajust P, Sena AG, Lai LYH, Prats-Uribe A, Ahmed WU, Alshammari TM, Alghoul H, Alser O, Burn E, You SC, Areia C, Blacketer C, DuVall S, Falconer T, Fernandez-Bertolin S, Fortin S, Golozar A, Gong M, Tan EH, Huser V, Iveli P, Morales DR, Nyberg F, Posada JD, Recalde M, Roel E, Schilling LM, Shah NH, Shah K, Suchard MA, Zhang L, Zhang Y, Williams AE, Reich CG, Hripcsak G, Rijnbeek P, Ryan P, Kostka K, Prieto-Alhambra D. Duarte-Salles T, et al. Pediatrics. 2021 Sep;148(3):e2020042929. doi: 10.1542/peds.2020-042929. Epub 2021 May 28. Pediatrics. 2021. PMID: 34049958

Abstract

Objectives To characterize the demographics, comorbidities, symptoms, in-hospital treatments, and health outcomes among children/adolescents diagnosed or hospitalized with COVID-19. Secondly, to describe health outcomes amongst children/adolescents diagnosed with previous seasonal influenza. Design International network cohort. Setting Real-world data from European primary care records (France/Germany/Spain), South Korean claims and US claims and hospital databases. Participants Diagnosed and/or hospitalized children/adolescents with COVID-19 at age <18 between January and June 2020; diagnosed with influenza in 2017-2018. Main outcome measures Baseline demographics and comorbidities, symptoms, 30-day in-hospital treatments and outcomes including hospitalization, pneumonia, acute respiratory distress syndrome (ARDS), multi-system inflammatory syndrome (MIS-C), and death. Results A total of 55,270 children/adolescents diagnosed and 3,693 hospitalized with COVID-19 and 1,952,693 diagnosed with influenza were studied. Comorbidities including neurodevelopmental disorders, heart disease, and cancer were all more common among those hospitalized vs diagnosed with COVID-19. The most common COVID-19 symptom was fever. Dyspnea, bronchiolitis, anosmia and gastrointestinal symptoms were more common in COVID-19 than influenza. In-hospital treatments for COVID-19 included repurposed medications (<10%), and adjunctive therapies: systemic corticosteroids (6.8% to 37.6%), famotidine (9.0% to 28.1%), and antithrombotics such as aspirin (2.0% to 21.4%), heparin (2.2% to 18.1%), and enoxaparin (2.8% to 14.8%). Hospitalization was observed in 0.3% to 1.3% of the COVID-19 diagnosed cohort, with undetectable (N<5 per database) 30-day fatality. Thirty-day outcomes including pneumonia, ARDS, and MIS-C were more frequent in COVID-19 than influenza. Conclusions Despite negligible fatality, complications including pneumonia, ARDS and MIS-C were more frequent in children/adolescents with COVID-19 than with influenza. Dyspnea, anosmia and gastrointestinal symptoms could help differential diagnosis. A wide range of medications were used for the inpatient management of pediatric COVID-19.

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Conflict of interest statement

Competing interest statement

All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: DV reports personal fees from Bayer, outside the submitted work, and full-time employment at Bayer. AG reports personal fees from Regeneron Pharmaceuticals, outside the submitted work; and she a full-time employee at Regeneron Pharmaceuticals. GH reports grants from US National Library of Medicine, during the conduct of the study; grants from Janssen Research, outside the submitted work. AS reports personal fees from Janssen Research & Development, during the conduct of the study; personal fees from Janssen Research & Development, outside the submitted work. SF is an employee of Janssen, Research and Development, a subsidiary of Johnson & Johnson. PR is an employee of Janssen Research and Development and shareholder of Johnson & Johnson. KK and CR report being employees of IQVIA. MS reports grants from US National Institutes of Health, grants from Department of Veterans Affairs, during the conduct of the study; grants from IQVIA, personal fees from Janssen Research and Development, outside the submitted work. DPA reports grants and other from AMGEN, grants, non-financial support and other from UCB Biopharma, grants from Les Laboratoires Servier, outside the submitted work; and Janssen, on behalf of IMI-funded EHDEN and EMIF consortiums, and Synapse Management Partners have supported training programs organized by DPA’s department and open for external participants. FN was an employee of AstraZeneca until 2019 and holds some AstraZeneca shares. The views expressed are those of the authors and do not necessarily represent the views or policy of the Department of Veterans Affairs or the United States Government. No other relationships or activities that could appear to have influenced the submitted work.

Figures

**Figure 1.. Database selection process**
Colorado University Anschuz Medical Campus Health Data Compass (CU-AMC HDC), Columbia University Irving Medical Center (CUIMC), Clinical Practice Research Datalink (CPRD), Data Analyzer (DA), Daegu Catholic University Medical Center (DCMC), Health Insurance Review & Assessment Service (HIRA), Integrated Primary Care Information (IPCI), Longitudinal Patient Data (LPD), Nanfang Hospital COVID-19 Research Database (NFHCRD), Information System for Research in Primary Care (SIDIAP), STAnford medicine Research data Repository (STARR-OMOP), Tufts Research Data Warehouse (TRDW), Department of Veterans Affairs (VA-OMOP) *No prior observation time available and therefore excluded from description of comorbidities.

**Figure 2.**
Prevalence of previous comorbidities among children/adolescents (<18 years of age) diagnosed (X axis) compared to hospitalized (Y axis) with COVID-19. SMD = Standardized Mean Differences in prevalence between X and Y.

**Figure 3.**
Symptoms recorded at index date among children/adolescents (<18 years of age)

**Figure 4.**
30-day in-hospital use of treatments among children/adolescents (<18 years of age) with COVID-19

**Figure 5.**
Main 30-day outcomes among children/adolescents (<18 years of age)

See this image and copyright information in PMC

References

1. World Health Organization (WHO) [Internet]. WHO Coronavirus Disease (COVID-19) Dashboard [cited 2020 Sep 19]. Available from: https://covid19.who.int/
1. Dong Y, Mo X, Hu Y, et al. Epidemiology of COVID-19 among children in China. Pediatrics. 2020;145(6):e20200702. - PubMed
1. He J, Guo Y, Mao R, Zhang J. Proportion of asymptomatic coronavirus disease 2019: a systematic review and meta-analysis. J Med Virol. 2020;10.1002/jmv.26326 - DOI - PMC - PubMed
1. Kim L, Whitaker M, O’Halloran A, et al. Hospitalization Rates and Characteristics of Children Aged <18 Years Hospitalized with Laboratory-Confirmed COVID-19 - COVID-NET, 14 States, March 1-July 25, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(32):1081–1088. - PMC - PubMed
1. CDC COVID-19 Response Team. Coronavirus Disease 2019 in Children — United States, February 12–April 2, 2020. MMWR Morb Mortal Wkly Rep. 2020;69(14):422–426. - PMC - PubMed

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This is a preprint.

Baseline characteristics, management, and outcomes of 55,270 children and adolescents diagnosed with COVID-19 and 1,952,693 with influenza in France, Germany, Spain, South Korea and the United States: an international network cohort study

Affiliations

Baseline characteristics, management, and outcomes of 55,270 children and adolescents diagnosed with COVID-19 and 1,952,693 with influenza in France, Germany, Spain, South Korea and the United States: an international network cohort study

Authors

Affiliations

Update in

Abstract

Conflict of interest statement

Figures

References

Publication types

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