• Marija Lugar, Anne Eugster, Peter Achenbach, Thekla von dem Berge, Reinhard Berner, BesserRachel E JREJDepartment of Pediatrics, University of Oxford, Oxford, United Kingdom.Wellcome Centre for Human Genetics, Nuffield Department of Medicine, NIHR Oxford Biomedical Research Centre, Oxford University, Oxford, United Kingdom., Kristina Casteels, Helena Elding Larsson, Gita Gemulla, Olga Kordonouri, Annett Lindner, Markus Lundgren, Denise Müller, Mariusz Oltarzewski, Anne Rochtus, Marlon Scholz, Agnieszka Szypowska, John A Todd, Anette-Gabriele Ziegler, Ezio Bonifacio, and GPPAD Study Group.
• Technische Universität Dresden, Center for Regenerative Therapies Dresden, Dresden, Germany.
• JAMA. 2023 Sep 26; 330 (12): 115111601151-1160.

ImportanceThe incidence of diabetes in childhood has increased during the COVID-19 pandemic. Elucidating whether SARS-CoV-2 infection is associated with islet autoimmunity, which precedes type 1 diabetes onset, is relevant to disease etiology and future childhood diabetes trends.ObjectiveTo determine whether there is a temporal relationship between SARS-CoV-2 infection and the development of islet autoimmunity in early childhood.Design, Setting, And ParticipantsBetween February 2018 and March 2021, the Primary Oral Insulin Trial, a European multicenter study, enrolled 1050 infants (517 girls) aged 4 to 7 months with a more than 10% genetically defined risk of type 1 diabetes. Children were followed up through September 2022.ExposureSARS-CoV-2 infection identified by SARS-CoV-2 antibody development in follow-up visits conducted at 2- to 6-month intervals until age 2 years from April 2018 through June 2022.Main Outcomes And MeasuresThe development of multiple (≥2) islet autoantibodies in follow-up in consecutive samples or single islet antibodies and type 1 diabetes. Antibody incidence rates and risk of developing islet autoantibodies were analyzed.ResultsConsent was obtained for 885 (441 girls) children who were included in follow-up antibody measurements from age 6 months. SARS-CoV-2 antibodies developed in 170 children at a median age of 18 months (range, 6-25 months). Islet autoantibodies developed in 60 children. Six of these children tested positive for islet autoantibodies at the same time as they tested positive for SARS-CoV-2 antibodies and 6 at the visit after having tested positive for SARS-CoV-2 antibodies. The sex-, age-, and country-adjusted hazard ratio for developing islet autoantibodies when the children tested positive for SARS-CoV-2 antibodies was 3.5 (95% CI, 1.6-7.7; P = .002). The incidence rate of islet autoantibodies was 3.5 (95% CI, 2.2-5.1) per 100 person-years in children without SARS-CoV-2 antibodies and 7.8 (95% CI, 5.3-19.0) per 100 person-years in children with SARS-CoV-2 antibodies (P = .02). Islet autoantibody risk in children with SARS-CoV-2 antibodies was associated with younger age (<18 months) of SARS-CoV-2 antibody development (HR, 5.3; 95% CI, 1.5-18.3; P = .009).Conclusion And RelevanceIn young children with high genetic risk of type 1 diabetes, SARS-CoV-2 infection was temporally associated with the development of islet autoantibodies.

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