#parent | #kids | COVID-19 in children and adolescents in Europe: a multinational, multicentre cohort study | #covid19 | #kids | #childern


Summary

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.

Introduction

In late December, 2019, WHO was notified of an unusual cluster of pneumonia cases in Wuhan, China. The disease, later termed COVID-19, spread quickly beyond the borders of China, with the first cases in Europe being recorded on Jan 25, 2020.

1

WHO
Novel coronavirus (2019-nCoV) situation report 5.

Subsequent investigations identified a novel betacoronavirus now designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

2

Coronaviridae Study Group of the International Committee on Taxonomy of Viruses
The species severe acute respiratory syndrome-related coronavirus: classifying 2019-nCoV and naming it SARS-CoV-2.

Currently, there are no antiviral treatment options with proven efficacy, but several randomised controlled trials are investigating agents such as hydroxychloroquine, lopinavir–ritonavir, favipiravir, and remdesivir (eg, NCT04336904, NCT04328285, and NCT04280705). Other trials are focusing on immunomodulators, including tocilizumab and anakinra (eg, NCT04317092 and NCT04330638).

To date, data on COVID-19 in children and adolescents remain scarce, despite the number of confirmed COVID-19 cases now exceeding 8 million globally.

3

WHO
Novel coronavirus (2019-nCoV) situation report 148.

4

Zimmermann P, Goetzinger F, Ritz N. Severe and fatal COVID-19 occurs in young children. JAMA Pediatrics (in press).

Most published data originate from China, which cannot necessarily be extrapolated to children in Europe and elsewhere.

5

Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding.

6

Novel Coronavirus Pneumonia Emergency Response Epidemiology Team
The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China.

7

  • Chen H
  • Guo J
  • Wang C
  • et al.

Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records.

8

  • Zhu L
  • Wang J
  • Huang R
  • et al.

Clinical characteristics of a case series of children with coronavirus disease 2019.

9

  • Castagnoli R
  • Votto M
  • Licari A
  • et al.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents: a systematic review.

10

SARS-CoV-2 infection in children.

11

Epidemiology of COVID-19 among children in China.

12

  • Liu W
  • Zhang Q
  • Chen J
  • et al.

Detection of Covid-19 in children in early January 2020 in Wuhan, China.

Also, existing papers from China contain very few clinical data on children, and most lack details regarding supportive measures required by children with COVID-19. Similarly, recent epidemiological reports from Europe and North America contain little clinically relevant information.

13

  • Gudbjartsson DF
  • Helgason A
  • Jonsson H
  • et al.

Spread of SARS-CoV-2 in the Icelandic population.

14

CDC COVID-19 Response Team
Coronavirus disease 2019 in children—United States, February 12–April 2, 2020.

Determining the level of support required by children is essential for paediatric service planning during the ongoing COVID-19 pandemic.