Asymptomatic SARS-CoV-2 Detection in Children
Asymptomatic SARS-CoV-2 Detection in Children
The primary objective of this study is quantify the transmission risk posted by SARS-CoV-2 in
 pre/asymptomatic infected children in order to inform the public health response to the
 COVID-19 pandemic.
1. Background & Rationale:

 Background: Transmission from individuals with pre-symptomatic and asymptomatic
 (hereafter abbreviated as pre/asymptomatic) SARS-CoV-2 infections is the Achilles' heel
 of COVID-19 pandemic control1. While pediatric SARS-CoV-2 infection is yet to be fully
 characterized, and generally children are more likely to experience asymptomatic
 infection or mild disease compared with adults, severe outcomes are possible. Although
 person-to-person spread is well described in children, as schools have been closed, the
 transmission risk in that environment remains unknown. More importantly, the
 contribution of pre/asymptomatic children to overall transmission of SARS-CoV-2 is
 unclear with most pediatric cases linked to a symptomatic household member. According to
 China's National Health Commission, 130 (78%) of 166 new infections identified on April
 1, 2020 were asymptomatic. In addition, data from an adult long-term care facility in
 Washington indicates that symptom-based screening failed to identify a significant
 proportion of COVID-19 cases. Furthermore, based on RT-PCR cycle threshold values, large
 quantities of viral RNA were detected in pre/asymptomatic residents, suggesting the
 potential for transmission regardless of symptoms. Asymptomatic pediatric colonization,
 while reported, is poorly described.

 Rationale: SARS-CoV-2 shedding has been noted to occur in minimally symptomatic and
 asymptomatic infected persons. Children therefore, who appear to more commonly
 experience mild and asymptomatic infection, may represent a significant risk of
 household and community transmission. Recommendations for school closures are currently
 based on assumptions as well as evidence gathered from influenza outbreaks where these
 measures are known to reduce social contacts and interrupt transmission. School
 closures, however, disrupt the lives of students and their families and may have
 negative consequences on child health16. Moreover, COVID-19 transmission modelling
 studies predict that school closures alone prevent only 2 - 4% of COVID-19-related
 deaths in the general population, much less than other physical distancing
 interventions. It should be noted that as school closures were in place before
 observational studies could begin, the secondary clinical attack rate of
 pre/asymptomatic children is unknown.

 2. Research Questions & Objectives:

 The primary objective of this study is quantify the transmission risk posted by
 SARS-CoV-2 in pre/asymptomatic infected children in order to inform the public health
 response to the COVID-19 pandemic by determining the following:

 If the proportion of household members who develop symptomatic illness over the
 subsequent 12 days is greater among households of pre/asymptomatic SARS-CoV-2 positive
 children relative to negative children. Mathematical models will be developed to
 understand the risks associated with other community transmission settings.

 In SARS-CoV-2 positive children, if quantitative viral loads differ between those who
 become symptomatic relative to those who remain asymptomatic and have secondary
 household cases.

 Secondary aims of this study include the following:

 Determining risk factors for SARS-CoV-2 pre/asymptomatic infection in children.

 3. Study Design and Methods:

 A prospective cohort study, taking place at multiple institutions throughout the United
 States and Canada, of children brought to the Emergency Department for care due to a
 condition or illness unrelated to SARS-CoV-2 infection who are tested as part of ongoing
 local asymptomatic surveillance programs.

 For every SARS-CoV-2-positive asymptomatic child enrolled, three asymptomatic SARS-CoV-2-test
 negative children will also be recruited.

 Any child that is tested for the presence of SARS-CoV-2 who is asymptomatic as part of
 clinical care, will be potentially eligible for the study. Locally, any child who is tested
 for the presence of SARS-CoV-2 and who is not displaying any known COVID-19 symptoms will be
 asked by an Alberta Health Services ED staff member for consent to provide their information
 to the research team to be contacted about potential participation in the study (consent to
 contact). Due to testing result timelines and to minimize possible exposure, informed
 consent/assent will be obtained via telephone and a copy of the consent documentation will be
 sent via email to the consenting individual, if required. Eligibility for the study based on
 inclusion and exclusion criteria will be determined over the telephone. Data will be obtained
 from the participant, their caregiver, and their medical chart, as appropriate. To obtain
 data related to symptomology, additional medical care, additional testing, and household
 transmission, a follow up questionnaire will be performed 14 days after the baseline ED
 visit. If a member of the household is waiting on SARS-CoV-2 testing results at the 14 day
 follow up time point, an additional call will be made 21 days after the baseline ED visit to
 obtain SARS-CoV-2 test results. A follow-up call will be performed at 90 days to identify any
 chronic symptoms that may have developed.
Inclusion Criteria:

 -  Younger than 18 years of age

 -  Had SARS-CoV-2 NAT testing performed during the ED visit as part of an ongoing active
 asymptomatic surveillance program:

 1. Exposed (SARS-CoV-2 positive) specific: Was found positive by SARS-CoV-2 NAT
 testing in the ongoing active surveillance program

 2. Unexposed (SARS-CoV-2 negative/control) specific: Was found negative by
 SARS-CoV-2 NAT testing in the ongoing active surveillance program

 Exclusion Criteria:

 -  Presence of any of the following viral symptoms commonly associated with SARS-CoV- 2
 infection: fever, cough, dyspnea/difficulty breathing, generalized fatigue/weakness,
 myalgia (muscle or body aches), chills, feeling very unwell, sore throat, runny nose,
 gastrointestinal symptoms (vomiting, diarrhea), conjunctivitis, headache, anosmia
 (loss of smell), ageusia (loss of taste) or rash in the 24 hours preceding the index
 visit (when the child was tested for the presence of SARS-CoV-2).

 -  Previously diagnosed with SARS-CoV-2 infection based on a positive swab or serology
 (blood) test.

 -  Decline to provide informed consent and/or assent, as required