SARS-CoV-2 Infection and Development of Islet Autoimmunity in Early Childhood

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Marija Lugar - , TUD Dresden University of Technology (Author)
  • Anne Eugster - , TUD Dresden University of Technology (Author)
  • Peter Achenbach - , Helmholtz Zentrum München - German Research Center for Environmental Health, Klinikum Rechts der Isar (MRI TUM) (Author)
  • Thekla Von Dem Berge - , Children's Hospital Auf der Bult (Author)
  • Reinhard Berner - , Department of Paediatrics (Author)
  • Rachel E.J. Besser - , University of Oxford (Author)
  • Kristina Casteels - , KU Leuven (Author)
  • Helena Elding Larsson - , Lund University (Author)
  • Gita Gemulla - , Center for Regenerative Therapies Dresden, Department of Paediatrics (Author)
  • Olga Kordonouri - , Children's Hospital Auf der Bult (Author)
  • Annett Lindner - , TUD Dresden University of Technology (Author)
  • Markus Lundgren - , Lund University, Kristianstad Hospital (Author)
  • Denise Müller - , TUD Dresden University of Technology (Author)
  • Mariusz Oltarzewski - , Institute of Mother and Child (Author)
  • Anne Rochtus - , KU Leuven (Author)
  • Marlon Scholz - , Technical University of Munich, Helmholtz Zentrum München - German Research Center for Environmental Health (Author)
  • Agnieszka Szypowska - , Medical University of Warsaw (Author)
  • John A. Todd - , University of Oxford (Author)
  • Anette Gabriele Ziegler - , Helmholtz Zentrum München - German Research Center for Environmental Health, Klinikum Rechts der Isar (MRI TUM) (Author)
  • Ezio Bonifacio - , Center for Regenerative Therapies Dresden, Chair of Preclinical stem cell therapy and diabetes, Helmholtz Zentrum München - German Research Center for Environmental Health (Author)

Abstract

Importance: The 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. Objective: To determine whether there is a temporal relationship between SARS-CoV-2 infection and the development of islet autoimmunity in early childhood. Design, Setting, and Participants: Between 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. Exposure: SARS-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 Measures: The 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. Results: Consent 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 relevance: In young children with high genetic risk of type 1 diabetes, SARS-CoV-2 infection was temporally associated with the development of islet autoantibodies..

Details

Original languageEnglish
Pages (from-to)1151-1160
Number of pages10
JournalJAMA
Volume330
Issue number12
Publication statusPublished - 26 Sept 2023
Peer-reviewedYes

External IDs

PubMed 37682551
ORCID /0000-0002-8704-4713/work/149436785

Keywords

Sustainable Development Goals

ASJC Scopus subject areas

Keywords

  • Genetic Predisposition to Disease, Pandemics, COVID-19/complications, Humans, Islets of Langerhans/immunology, Autoantibodies/immunology, Child, Preschool, Infant, Male, Antibodies, Viral/immunology, SARS-CoV-2, Autoimmunity/immunology, Diabetes Mellitus, Type 1/etiology, Female