COVID-19 infection increases risk of type 1 diabetes among young children with high genetic risk: JAMA

"The incidence rate of islet autoantibodies developing concurrently with or soon after SARS-CoV-2 antibodies were detected was 7.8 per 100 person-years and in children without SARS-CoV-2 antibodies it was 3.5 per 100 person-years, a significant difference," the researchers reported.

Childhood type 1 diabetes is characteristically preceded by the development of antibodies against multiple pancreatic islet β-cell proteins. The researchers noted a peak period of susceptibility for developing these autoantibodies at about 1 year of age. Children who develop multiple islet autoantibodies usually advance to clinical type 1 diabetes within ten years.

Susceptibility for early islet autoimmunity is conferred by genes involved in islet β-cell function, immunity, and responses to viral infections. There is no clarity on the cause of islet autoimmunity, suspected contributors include early viral infections.

During the COVID-19 pandemic, there has been an increase in the incidence of childhood diabetes. Elucidating whether SARS-CoV-2 infection is linked with islet autoimmunity, which precedes type 1 diabetes onset, is relevant to future childhood diabetes trends and disease aetiology.

Marija Lugar, Center for Regenerative Therapies Dresden, Dresden, Germany, and colleagues aimed to determine whether there is a temporal relationship between SARS-CoV-2 infection and the development of islet autoimmunity in early childhood.

The Primary Oral Insulin Trial, a European multicenter study enrolled 1050 infants (aged 4 to 7 months) between 2018 to 2021 with a more than 10% genetically defined risk of type 1 diabetes.

SARS-CoV-2 infection was identified by the development of SARS-CoV-2 antibody in follow-up visits conducted at 2- to 6-month intervals until age 2 years from 2018 to 2022.

The study's main outcome was the development of multiple (≥2) islet autoantibodies in follow-up in consecutive samples or single islet antibodies and type 1 diabetes. The researchers analyzed antibody incidence and risk of developing islet autoantibodies.

The authors reported the following findings:

• 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.
• 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.
• The incidence rate of islet autoantibodies was 3.5 per 100 person-years in children without SARS-CoV-2 antibodies and 7.8 per 100 person-years in children with SARS-CoV-2 antibodies.
• 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).

"SARS-CoV-2 infection was temporally associated with the development of islet autoantibodies in young children with high genetic risk of type 1 diabetes," the researchers concluded.

Reference:

Lugar M, Eugster A, Achenbach P, et al. SARS-CoV-2 Infection and Development of Islet Autoimmunity in Early Childhood. JAMA. Published online September 08, 2023. doi:10.1001/jama.2023.16348