Environmental triggers of pediatric type 1 diabetes: A protocol for a systematic review and meta-analysis on the impact of COVID-19 infection and vaccination

Introduction
The study aimed to systematically evaluate whether coronavirus disease (COVID-19) infection and/or vaccination act as environmental triggers for new-onset type 1 diabetes (T1D) in children and adolescents.

Material and methods
We will conduct a systematic review and meta-analysis in accordance with PRISMA 2020 guidelines. PubMed, Embase, Scopus, Web of Science, and Cochrane Library will be searched for studies from 2020 onward. Eligible studies must report new-onset T1D in individuals aged 0–19 years following confirmed SARS-CoV-2 infection or COVID-19 vaccination, with a clearly defined comparator group. Data will be extracted using the Population-Exposure-Comparator-Outcome (PECO) framework, aiming to capture diabetes incidence, diabetic ketoacidosis (DKA) severity, immunologic and genetic markers, direction of effect, and potential confounders. Risk of bias will be assessed with the Newcastle–Ottawa Scale, and GRADE will be used to assess certainty of evidence. A random-effects meta-analysis will be conducted if appropriate.

Expected results
We anticipate mapping the direction of effect (­, ¯, mixed, or = no difference) for each exposure–outcome pair, and identifying gaps related to immunologic markers, diagnostic timing, and confounding factors.

Conclusions
This review will provide a comprehensive synthesis of evidence on infection- and vaccine-triggered pediatric T1D, informing future prospective studies and surveillance efforts.