SARS-CoV-2 Infection and Development of Islet Autoimmunity in Early Childhood
Authors: Lugar Marija , Eugster Anne , Achenbach Peter , von dem Berge Thekla , Berner Reinhard , Besser Rachel E. J. , Casteels Kristina , Elding Larsson Helena , Gemulla Gita , Kordonouri Olga , Lindner Annett , Lundgren Markus , Müller Denise , Oltarzewski Mariusz , Rochtus Anne , Scholz Marlon , Szypowska Agnieszka , Todd John A. , Ziegler Anette-Gabriele , Bonifacio Ezio ,   GPPAD Study Group, Gündert Melanie , Haupt Florian , Arnolds Stefanie , Blasius Karina , Friedl Nadine , Gezginci Cigdem , Göppel Gertrud , Heigermoser Martin , Hergl Maja , Höfelschweiger Bianca , Jolink Manja , Kisfügedi Krisztian , Klein Nadine , Matzke Claudia , Niewöhner Rebecca , Schütte-Borkovec Katharina , Weiß Andreas , Zapardiel Gonzalo José Maria , Schmidt Sarah , Vurucu Merve , Sarcletti Katharina , Sporreiter Melanie , Jacobson Stefanie , Janssen Charlien , Morobé Hilde , Vrancken Brontë , Van den Driessche Natalie , Van Poel Gert , Van Heyste Renka , Houben Janne , Vanhuyse Veerle , Arabi Sari , Barbknecht Lisa , Dietz Sevina , Ehrlich Franziska , Gholizadeh Zahra , Hoffmann Raphael , Hommel Angela , Lange Franziska , Loff Anja , Morgenstern Robert , Schille Anne , Sigg Maike , Weigelt Marc , Weise Andre , Zubizarreta  Nicole , Danne Thomas , Galuschka Laura , Kruse Carolin , Landsberg Sarah , Lange Karin , Marquardt Erika , Reschke Felix , Roloff Frank , Weiskorn Jantje , Polier Mareike , Schmidt Bianca , Bunk Melanie , Hofelich Anna , Huber Elisabeth , Kaiser Melina , Käßl Alexandra , Marcus Benjamin , Munzinger Annette , Ramminger Claudia , Reinmüller Franziska , Vollmuth Veronika , Winkler Christiane , Dybkowska Sylwia , Groele Lidia , Owczarek Dorota , Popko Katarzyna , Cieloch Adrianna , Dzygalo Katarzyna , Górska Elżbieta , Mroczek Agnieszka , Zduńczyk Beata , Zych Anna , Czerwińska Wiktoria , Dziedzic Natalia , Samuelsson Hanna , Alström Mortin Sofie , Bennet Rasmus , Brundin Charlotte , Dahlberg Susanne , Fransson Lina , Jönsson Ida , Nenonen Hannah , Ramelius Anita , Törn Carina , Ulvenhag Ulrika , Lindström Marielle , Rhamati Kobra , Goldman Tsubarah Malin , Salami  Falastin , Hawkins Sophia , Mujadidi Yama F , Smith Ian , Roseman Fenella , Robinson Hannah , Taj Nazia , Whelan Conor , Wishlade Tabitha , Vernon Sophie , Ratcliffe Helen 
Published: September 2023

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 (&amp;lt;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.