COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study

TY - JOUR

T1 - COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study

AU - Götzinger, Florian

AU - Santiago-García, Begoña

AU - Noguera-Julián, Antoni

AU - Lanaspa, Miguel

AU - Lancella, Laura

AU - Calò Carducci, Francesca I

AU - Gabrovska, Natalia

AU - Velizarova, Svetlana

AU - Prunk, Petra

AU - Osterman, Veronika

AU - Krivec, Uros

AU - Lo Vecchio, Andrea

AU - Shingadia, Delane

AU - Soriano-Arandes, Antoni

AU - Melendo, Susana

AU - Lanari, Marcello

AU - Pierantoni, Luca

AU - Wagner, Noémie

AU - L'Huillier, Arnaud G

AU - Heininger, Ulrich

AU - Ritz, Nicole

AU - Bandi, Srini

AU - Krajcar, Nina

AU - Roglić, Srđan

AU - Santos, Mar

AU - Christiaens, Christelle

AU - Creuven, Marine

AU - Buonsenso, Danilo

AU - Welch, Steven B

AU - Bogyi, Matthias

AU - Brinkmann, Folke

AU - Tebruegge, Marc

AU - ptbnet COVID-19 Study Group

AU - Kobbe, Robin

AU - Rau, Cornelius

N1 - Copyright © 2020 Elsevier Ltd. All rights reserved.

PY - 2020/9

Y1 - 2020/9

N2 - BACKGROUND: To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic.METHODS: This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network-the Paediatric Tuberculosis Network European Trials Group (ptbnet)-that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission.FINDINGS: 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5-12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2-11, range 1-34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72-14·87; p=0·0035), male sex (2·12, 1·06-4·21; p=0·033), pre-existing medical conditions (3·27, 1·67-6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16-21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir-ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20-1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support.INTERPRETATION: COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed.FUNDING: ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit.

AB - BACKGROUND: To date, few data on paediatric COVID-19 have been published, and most reports originate from China. This study aimed to capture key data on children and adolescents with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection across Europe to inform physicians and health-care service planning during the ongoing pandemic.METHODS: This multicentre cohort study involved 82 participating health-care institutions across 25 European countries, using a well established research network-the Paediatric Tuberculosis Network European Trials Group (ptbnet)-that mainly comprises paediatric infectious diseases specialists and paediatric pulmonologists. We included all individuals aged 18 years or younger with confirmed SARS-CoV-2 infection, detected at any anatomical site by RT-PCR, between April 1 and April 24, 2020, during the initial peak of the European COVID-19 pandemic. We explored factors associated with need for intensive care unit (ICU) admission and initiation of drug treatment for COVID-19 using univariable analysis, and applied multivariable logistic regression with backwards stepwise analysis to further explore those factors significantly associated with ICU admission.FINDINGS: 582 individuals with PCR-confirmed SARS-CoV-2 infection were included, with a median age of 5·0 years (IQR 0·5-12·0) and a sex ratio of 1·15 males per female. 145 (25%) had pre-existing medical conditions. 363 (62%) individuals were admitted to hospital. 48 (8%) individuals required ICU admission, 25 (4%) mechanical ventilation (median duration 7 days, IQR 2-11, range 1-34), 19 (3%) inotropic support, and one (<1%) extracorporeal membrane oxygenation. Significant risk factors for requiring ICU admission in multivariable analyses were being younger than 1 month (odds ratio 5·06, 95% CI 1·72-14·87; p=0·0035), male sex (2·12, 1·06-4·21; p=0·033), pre-existing medical conditions (3·27, 1·67-6·42; p=0·0015), and presence of lower respiratory tract infection signs or symptoms at presentation (10·46, 5·16-21·23; p<0·0001). The most frequently used drug with antiviral activity was hydroxychloroquine (40 [7%] patients), followed by remdesivir (17 [3%] patients), lopinavir-ritonavir (six [1%] patients), and oseltamivir (three [1%] patients). Immunomodulatory medication used included corticosteroids (22 [4%] patients), intravenous immunoglobulin (seven [1%] patients), tocilizumab (four [1%] patients), anakinra (three [1%] patients), and siltuximab (one [<1%] patient). Four children died (case-fatality rate 0·69%, 95% CI 0·20-1·82); at study end, the remaining 578 were alive and only 25 (4%) were still symptomatic or requiring respiratory support.INTERPRETATION: COVID-19 is generally a mild disease in children, including infants. However, a small proportion develop severe disease requiring ICU admission and prolonged ventilation, although fatal outcome is overall rare. The data also reflect the current uncertainties regarding specific treatment options, highlighting that additional data on antiviral and immunomodulatory drugs are urgently needed.FUNDING: ptbnet is supported by Deutsche Gesellschaft für Internationale Zusammenarbeit.

KW - Betacoronavirus

KW - COVID-19

KW - Child

KW - Child, Preschool

KW - Coronavirus Infections/epidemiology

KW - Delivery of Health Care/organization & administration

KW - Europe/epidemiology

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Intensive Care Units/organization & administration

KW - Male

KW - Pandemics

KW - Patient Admission/trends

KW - Pneumonia, Viral/epidemiology

KW - Risk Factors

KW - SARS-CoV-2

U2 - 10.1016/S2352-4642(20)30177-2

DO - 10.1016/S2352-4642(20)30177-2

M3 - SCORING: Journal article

C2 - 32593339

VL - 4

SP - 653

EP - 661

JO - LANCET CHILD ADOLESC

JF - LANCET CHILD ADOLESC

SN - 2352-4642

IS - 9

ER -