Asymptomatic SARS-CoV-2 Detection in Children

• ClinicalTrials.gov Identifier: NCT04853316
• Recruitment Status: Active, not recruiting
• First Posted: April 21, 2021
• Last Update Posted: May 18, 2022
• Sponsor: University of Calgary
• Collaborator: Canadian Institutes of Health Research (CIHR)
• Information provided by (Responsible Party): University of Calgary

Tracking Information

• First Submitted Date: April 16, 2021
• First Posted Date: April 21, 2021
• Last Update Posted Date: May 18, 2022
• Actual Study Start Date: November 16, 2020
• Estimated Primary Completion Date: June 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 16, 2021)

Symptoms of COVID-19 in household members of participating children in the subsequent 14 days following enrollment [ Time Frame: 14 days ]

The clinical secondary attack rate (SAR) for households of participating children, which will be compared to generate the relative SAR for households of children with varying case and symptom statuses.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: April 16, 2021)

Viral Load of SARS-CoV-2 in positive children [ Time Frame: 14 days ]

The difference in typical viral loads between children of different symptom and case statuses, as well as those with and without clinical secondary cases.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: April 16, 2021)

Presence of epidemiological risk factors for SARS-CoV-2 infection [ Time Frame: 14 days ]

Risk factors such as exposures, travel, following public health policy. The frequency of such risk factors among participating children will allow for calculation of the relative risk of such factors.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Asymptomatic SARS-CoV-2 Detection in Children
• Official Title: Household Transmission Dynamics and Viral Load Among Asymptomatic SARS-CoV-2 Infected Children
• Brief Summary: 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.

Detailed Description

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.

• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

SARS-CoV-2 Testing will be performed according to local public health and institutional guidelines. For any participants who tested positive for the presence of SARS-CoV-2, an aliquot of the corresponding positive test will be obtained. Viral load quantification will be performed on any specimens obtained.

• Sampling Method: Non-Probability Sample
• Study Population: All children younger than 18 years of age presenting to a participating ED who meet institutional surveillance screening guidelines (i.e. present with a non-infectious, non-viral concern) and undergo SARS-CoV-2 testing. The number of children eligible may vary based on evolving SARS-CoV-2 testing procedures, public health policy, and patient volumes.

Condition

• Covid19
• SARS-CoV-2

• Intervention: Not Provided

Study Groups/Cohorts

• Case: Exposed (SARS-CoV-2 positive)
  Participants found positive by SARS-CoV-2 testing.
• Control: Unexposed (SARS-CoV-2 negative)
  Participants found negative by SARS-CoV-2 testing.

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: May 16, 2022): 372
• Original Estimated Enrollment (submitted: April 16, 2021): 1600
• Estimated Study Completion Date: June 30, 2022
• Estimated Primary Completion Date: June 30, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: up to 18 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, United States

Administrative Information

• NCT Number: NCT04853316
• Other Study ID Numbers: REB20-0609
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: University of Calgary
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Calgary
• Original Study Sponsor: Same as current
• Collaborators: Canadian Institutes of Health Research (CIHR)

Investigators

• Principal Investigator: Stephen Freedman, MD; University of Calgary

• PRS Account: University of Calgary
• Verification Date: May 2022