Pediatric Research Observing Trends and Exposures in COVID-19 Timelines (PROTECT): Protocol for a Multisite Longitudinal Cohort Study (Preprint)

Assessing the real-world effectiveness of COVID-19 vaccines and understanding the incidence and severity of SARS-CoV-2 illness in children is essential to inform policy and guide healthcare professionals advising parents and caregivers of children who test positive for SARS-CoV-2.

This report describes the objectives and methods for conducting the Pediatric Research Observing Trends and Exposures in COVID-19 Timelines (PROTECT) study. PROTECT is a longitudinal prospective pediatric cohort study designed to estimate SARS-CoV-2 incidence and COVID-19 vaccine effectiveness (VE) against infection among children aged 6 months to 17 years as well as differences in SARS-CoV-2 infection and vaccine response between children and adolescents.

The PROTECT multisite network was initiated in July 2021 and aims to enroll approximately 2,305 children across four U.S. locations and collect data over a two-year surveillance period; the enrollment target was based on prospective power calculations and account for expected attrition and nonresponse. Study sites recruit parents and legal guardians (PLGs) of age-eligible children participating in the existing HEROES-RECOVER network as well as from surrounding communities. Child demographics, medical history, COVID-19 exposure, vaccination history, and PLGs’ knowledge and attitudes about COVID-19 are collected at baseline and throughout the study. Mid-turbinate nasal specimens are self- or PLG-collected weekly, regardless of symptoms, for SARS-CoV-2 and influenza testing via reverse transcription-polymerase chain reaction (RT-PCR) assay, and the presence of COVID-like-illness (CLI) is reported. Children who test positive for SARS-CoV-2 or influenza or report CLI are monitored weekly by online surveys to report exposure and medical utilization until no longer ill. Children, with their PLG’s permission, may elect to contribute blood at enrollment, following SARS-CoV-2 infection, following COVID-19 vaccination, and at the end of the study period. PROTECT uses electronic medical records (EMR) linkages where available and verifies COVID-19 and influenza vaccinations through EMR or state vaccine registries.

Data collection began in July 2021 and is expected to continue through Spring 2023. As of 02/07/2022, 2,161 children are enrolled in PROTECT. Enrollment is ongoing at all study sites.

As COVID-19 vaccine products are authorized for use in pediatric populations, PROTECT study data will provide real-world estimates of VE in preventing infection. In addition, this prospective cohort provides a unique opportunity to further understand SARS-CoV-2 incidence, clinical course, and key knowledge gaps that may inform public health.