ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This longitudinal cohort study of 885 infants with high genetic risk of type 1 diabetes (T1D) explored the temporal association between SARS-CoV-2 infection and development of T1D–associated autoimmunity. The incidence rate of islet autoantibodies was higher in children with vs. without SARS-CoV-2 antibodies (7.8 vs. 3.5 per 100 person-years). Hence, SARS-CoV-2 infection appears temporally associated with the development of islet autoantibodies.

Several previous studies reported an increased incidence of clinical T1D and diabetic ketoacidosis during the COVID-19 pandemic (1). This could be due to the role of viral infections as triggers for T1D autoimmunity or a direct action of SARS-CoV2 on pancreatic β-cells.

This study shifted the focus to earlier asymptomatic stages in the natural history of T1D, defined by the appearance of autoantibodies in children at genetic risk of T1D. Identifying potential modifiable targets during these early stages would allow primary prevention strategies for T1D. The study examined a unique cohort recruited in the European multicenter Primary Oral Insulin Trial (POINT), focusing on infants 4-7 months-old with a genetically defined risk of T1D > 10%, originally recruited in 2018-2021 to a trial of oral insulin (2). SARS-CoV-2 infection was identified by SARS-CoV-2 antibody, and antibodies to influenza A (H1N1) were also measured.

SARS-CoV-2 antibodies developed in 170/885 children at median age 18 months (range 6-25 months), and 60 children developed islet autoantibodies. Islet autoantibodies were more likely to appear concurrent with or soon after the development of SARS-CoV-2 antibodies, but not with H1N1 antibodies. This association was strongest in children infected SARS-CoV-2 before age 18 months.

Although the findings are limited to a specific group, i.e. infants at high genetic risk of T1D, and SARS-CoV2 infection was detected by antibodies only (without PCR confirmation), these results are remarkable. These findings have prompted a vaccine trial (the Antiviral Action against Type 1 diabetes Autoimmunity (AVANT1A)) to assess whether vaccination against COVID-19 at age 6 months can prevent the development of islet autoantibodies in infants at increased genetic risk of T1D (https://www.gppad.org/de-en/avant1a/).

References: 1. D’Souza, D., et al., Incidence of Diabetes in Children and Adolescents During the COVID-19 Pandemic: A Systematic Review and Meta-Analysis. JAMA Netw Open. 2023;6(6):e2321281.2. Ziegler, A.G., et al., Oral insulin therapy for primary prevention of type 1 diabetes in infants with high genetic risk: the GPPAD-POInT (global platform for the prevention of autoimmune diabetes primary oral insulin trial) study protocol. BMJ Open. 2019;9(6):e028578.