SARS-CoV-2 infection not associated with autoimmunity related to T1D development

New evidence suggests a lack of association between SARS-CoV-2 infection and autoimmunity associated with the development of type 1 diabetes (T1D).

After screening more than 50,000 adolescent patients in different populations in Colorado and Bavaria, Germany, no association between infection and development was observed.

“Long-term follow-up of individuals with pre-existing autoimmunity is necessary to determine whether SARS-CoV-2 accelerates progression to clinical diabetes,” wrote study author Marian Rewers, MD, PhD, Barbara Davis Center for Diabetes, University of Colorado School of medicine.

An increased incidence of clinical diabetes has been reported in children with prior COVID-19 infection. Rewers and colleagues therefore concluded that it might be plausible that the virus might trigger an autoimmune response to the islets or accelerate metabolic decompensation in individuals with established islet autoimmunity.

The hypothesis tested was that previous SARS-CoV-2 infection was associated with an autoimmunity that predicts future T1D. In 2020 and 2021, individuals ages 1 to 18 enrolled in the Autoimmunity Screening for Kids (ASK) in Colorado and children ages 1 to 10.9 enrolled in the Fr1da study in Germany , a cross-sectional screening for islet autoantibodies.

Autoantibody-negative children were also examined after detection of SARS-CoV-2 antibodies with blood sampling every 3 months in Bavaria.

The study defined past SARS-CoV-2 infection by the presence of antibodies against both the SARS-CoV-2 receptor binding domain and nucleocapsid proteins. In addition, autoantibodies against insulin, glutamic acid decarboxylase, islet antigen 2 and zinc transporter 8 autoantibodies were measured using comparable methods.

Study results included the presence of multiple or single high-affinity islet autoantibodies, which carry a 50% and 30% risk of progression to clinical diabetes at 5 years, respectively. Researchers used multivariable logistic regression to assess independent associations between prior infections and islet autoimmunity and to test for interactions by study site.

Results identified prior SARS-CoV-2 infection in 1524 (32.3%) of 4717 Colorado youth (mean age 8.6 years; 50.3% female) and 2862 (6.1%) of 47,253 Bavarian youth children (mean age 3.9 years; 48.9% female).

Data show that multiple islet autoantibodies were detected in 21 adolescents from Colorado (0.45%) and 141 Bavarian children (0.30%). In addition, 26 (0.55%) and 54 (0.11%) of the adolescents from Colorado and Bavaria, respectively, were positive for a single high-affinity islet autoantibody.

Investigators found that the prevalence of multiple or single high-affinity islet autoantibodies did not differ significantly between adolescents with prior SARS-CoV-2 infection compared to those without prior infection in Colorado (1.18% vs. 0.91%, P = 0.43) or Bavaria (0.42% vs. 0.41%; P = 0.88).

The results also suggest that prior infection was not significantly associated with the presence of multiple islet autoantibodies (odds ratio 1.06 [95% CI, 0.59 – 1.80]; P = 0.83) or a single high-affinity islet autoantibody (odds ratio 1.34 [95% CI, 0.70 – 2.44]; P = 0.36) after controlling for the confounders.

No significant interaction was reported between study site and association with SARS-CoV-2 infection, gender, age, or family history of T1D.

Rewers pointed out that limitations of the study include the low prevalence of autoantibodies, which weakens the ability to detect an increase in risk associated with SARS-CoV-2 infection. In addition, the cross-sectional design did not allow determining the timing of autoantibody development before or after infection.

The study “SARS-CoV-2 Infections and Presymptomatic Type 1 Diabetes Autoimmunity in Children and Adolescents from Colorado, USA, and Bavaria, Germany” was published in JAMA.