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COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study
Florian Götzinger1, Begoña Santiago-García2, Antoni Noguera-Julián3
1Department of Paediatric and Adolescent Medicine, National Reference Centre for Childhood Tuberculosis, Wilhelminenspital, Vienna, Austria.
Insights
Severe COVID-19 in children is rare but can occur, especially in infants, males, and those with pre-existing conditions. This European study highlights the need for more research on effective treatments for pediatric SARS-CoV-2 infection.
Area of Science:
- Pediatric Infectious Diseases
- Virology
- Epidemiology
Background:
- Limited data on pediatric COVID-19 (SARS-CoV-2) existed, primarily from China.
- European data were needed for physicians and health-care planning during the pandemic.
Purpose of the Study:
- To capture key data on children and adolescents with SARS-CoV-2 infection across Europe.
- To identify factors associated with severe disease requiring intensive care unit (ICU) admission.
Main Methods:
- Multicentre cohort study across 25 European countries.
- Included 582 individuals aged 18 or younger with confirmed SARS-CoV-2 infection (April 1-24, 2020).
- Used logistic regression to analyze factors associated with ICU admission.
Main Results:
- 8% of children required ICU admission; risk factors included age <1 month, male sex, pre-existing conditions, and lower respiratory tract symptoms.
- The case-fatality rate was 0.69%.
- Uncertainty remains regarding optimal antiviral and immunomodulatory treatments.
Conclusions:
- While generally mild, a small proportion of children develop severe COVID-19 requiring intensive care.
- Infants, males, and children with pre-existing conditions are at higher risk for severe disease.
- Further research on pediatric COVID-19 treatments is urgently needed.
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.
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