Clinical Characteristics and Outcomes of Pediatric COVID-19
Condition: COVID-19; SARS-CoV-2 Infection; Pediatric ALL; Pneumonia, Viral; Pandemic Response
MeSH terms: COVID-19; Pneumonia, Viral
Study type: Observational

Summary: 
      Rationale: The clinical manifestations of SARS-CoV-2 infection in children are poorly
      characterized. Preliminary findings indicate that they may be atypical. There is a need to
      identify the spectrum of clinical presentations, predictors of severe disease (COVID-19)
      outcomes, and successful treatment strategies in this population.

      Goals:

      Primary - Describe and compare characteristics of confirmed SARS-CoV-2 infected children with
      symptomatic test-negative children.

      Secondary - 1) Describe and compare confirmed SARS-CoV-2 infected children with mild versus
      severe COVID-19 outcomes; 2) Describe healthcare resource utilization for, and outcomes of,
      screening and care of pediatric COVID-19 internationally, alongside regional public health
      policy changes.

      Methods: This prospective observational study will occur in 50 emergency departments across
      11 countries. We will enroll 12,500 children who meet institutional screening guidelines and
      undergo SARS-CoV-2 testing. Data collection focuses on epidemiological risk factors,
      demographics, signs, symptoms, interventions, laboratory testing, imaging, and outcomes.
      Collection will occur at enrollment, 14 days, and 90 days.

      Timeline: Recruitment will last for 12 months (worst-case model) and will begin within 7-14
      days of funding notification after ongoing expedited review of ethics and data sharing
      agreements.

      Impact: Results will be shared in real-time with key policymakers, enabling rapid
      evidence-based adaptations to pediatric case screening and management.
    

Detailed description: 
      Pediatric COVID-19: The characteristics of pediatric 2019 novel coronavirus disease
      (COVID-19) are not yet well understood. Preliminary findings indicate that atypical
      presentations of COVID-19 occur in children. Thus, there is an urgent need to identify risk
      factors for pediatric COVID-19 infection, the range of clinical manifestations, predictors of
      severe outcomes, and successful treatment strategies.

      Objectives: Primary: To contribute to the optimization of medical countermeasures to
      pediatric COVID-19 through describing and comparing the clinical characteristics of
      SARS-CoV-2 infected children (i.e. test positive) with children who were screened for
      SARS-CoV-2 but tested negative. We will also describe and compare SARS-CoV-2 infected
      children with mild versus those with severe outcomes. This study will also describe the
      health care resources utilized for screening, isolation, and care of pediatric COVID-19,
      examined alongside relevant public health policies.

      Methods: This is a two-year prospective observational study that will take place at 50 EDs
      across 19 countries. We will enroll children (<18 years old) presenting to participating
      study EDs who meet institutional screening guidelines and undergo testing for COVID-19. Data
      collection is aligned with WHO templates and focuses on epidemiological factors,
      demographics, signs, symptoms, exposures, interventions, and test results. Collection will
      occur at the time of enrolment, during the course of illness, at hospital discharge (if
      admitted), and at two weeks and three months following enrolment. Over a period of 18 months
      (starting March 31st, 2020) we aim to enroll and complete follow-up for a total of 5000
      children with screened for suspected SARS-CoV-2 infection. Data will be entered into a
      centralized database, and analyzed using simple and multiple ordinal logistic regression
      models. Data will be interpreted alongside detailed, prospectively collected, information on
      the changes to case isolation, screening, and management policies that occur throughout the
      epidemic in each institution and study region.

      Feasibility: The Pediatric Emergency Research Networks (PERN) represents the largest
      international acute pediatric care collaboration in the world, including more than 200
      hospitals across 35 countries. Currently, PERN is carrying out the PERN-Pneumonia prospective
      cohort study, designed to identify predictors of severe pneumonia at 70 hospitals around the
      globe, including at eight Canadian pediatric emergency departments (ED). This study will
      build onto the PERN-Pneumonia study infrastructure (e.g. ethics approvals, data sharing
      agreements, research teams) in order to facilitate a unique, rapid, and global response to
      the COVID-19 epidemic. Feasibility is enhanced by our design - we will not interfere with the
      existing COVID-19 screening and management procedures in-place in study EDs; we will not
      collect any biological specimens, and will not prescribe any interventions.

      Project Team: This international multidisciplinary team includes pediatric emergency medicine
      and infectious disease clinicians, epidemiologists, statisticians, and public health leaders
      from around the globe. Team members have led many landmark trials in pediatric emergency
      medicine, and lead large pediatric research networks and studies including the PERN-Pneumonia
      study. They also came together to study the H1N1 pandemic and identified predictors of severe
      outcomes. Team members also have expertise in pediatric lower respiratory tract infections,
      biostatistics, and epidemiology (including the CDC lead on the MERS-CoV outbreak). This study
      team also includes the Public Health Agency of Canada's senior medical/technical expert on
      COVID-19.

      Impact of the research: The results of this study, which will be shared in real-time with
      appropriate national and international authorities, will enable policymakers to make rapid
      evidence-based adaptations to case screening and management procedures that will then allow
      for the earlier identification of children likely to have confirmed infection with COVID-19
      as well as to prioritize those children likely to have severe outcomes. Finally, the
      establishment of this global multi-site study will be the first trial of a rapid PERN
      networks response to a pandemic novel respiratory virus, which, applying lessons-learned, can
      be urgently reactivated for future public health emergencies.
    

Intervention name(s): Exposure (not intervention) - SARS-CoV-2 infection
Intervention type(s): Other
Intervention description(s): Exposure is infection with the virus. There is no intervention
Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        All children presenting to a participating ED who are screened (i.e. tested) for SARS-CoV-2
        during the duration of the study. Children will be mainly from urban areas across Canada,
        United States of America, Italy, Spain, Australia, New Zealand, Argentina, Singapore, and
        other countries.