Pediatric Research Observing Trends and Exposures in COVID-19 Timelines (PROTECT): Protocol for a Multisite Longitudinal Cohort Study
Authors: Burns Joy , Rivers Patrick , LeClair Lindsay B , Jovel Krystal S , Rai Ramona P , Lowe Ashley A , Edwards Laura J , Khan Sana M , Mathenge Clare , Ferraris Maria , Kuntz Jennifer L , Lamberte Julie Mayo , Hegmann Kurt T , Odean Marilyn J , McLeland-Wieser Hilary , Beitel Shawn , Odame-Bamfo Leah , Schaefer Solle Natasha , Mak Josephine , Phillips Andrew L , Sokol Brian E , Hollister James , Ochoa Jezahel S , Grant Lauren , Thiese Matthew S , Jacoby Keya B , Lutrick Karen , Pubillones Felipe A , Yoo Young M , Rentz Hunt Danielle , Ellingson Katherine , Berry Mark C , Gerald Joe K , Lopez Joanna , Gerald Lynn B , Wesley Meredith G , Krupp Karl , Herring Meghan K , Madhivanan Purnima , Caban-Martinez Alberto J , Tyner Harmony L , Meece Jennifer K , Yoon Sarang K , Fowlkes Ashley L , Naleway Allison L , Gwynn Lisa , Burgess Jefferey L , Thompson Mark G , Olsho Lauren EW , Gaglani Manjusha 
Published: May 2022

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

Objective
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.

Methods
The PROTECT multisite network was initiated in July 2021, which aims to enroll approximately 2305 children across four US locations and collect data over a 2-year surveillance period. The enrollment target was based on prospective power calculations and accounts for expected attrition and nonresponse. Study sites recruit parents and legal guardians of age-eligible children participating in the existing Arizona Healthcare, Emergency Response, and Other Essential Workers Surveillance (HEROES)-Research on the Epidemiology of SARS-CoV-2 in Essential Response Personnel (RECOVER) network as well as from surrounding communities. Child demographics, medical history, COVID-19 exposure, vaccination history, and parents/legal guardians’ knowledge and attitudes about COVID-19 are collected at baseline and throughout the study. Mid-turbinate nasal specimens are self-collected or collected by parents/legal guardians 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 permission of their parents/legal guardians, 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 record (EMR) linkages where available, and verifies COVID-19 and influenza vaccinations through EMR or state vaccine registries.

Results
Data collection began in July 2021 and is expected to continue through the spring of 2023. As of April 13, 2022, 2371 children are enrolled in PROTECT. Enrollment is ongoing at all study sites.

Conclusions
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.

International Registered Report Identifier (IRRID)
RR1-10.2196/37929