SARS-CoV-2 Infection Not Associated with Autoimmunity Related to T1D Development

Marian Rewers, MD, PhD

New findings suggest a lack of association between SARS-CoV-2 infection and autoimmunity related to the development of type 1 diabetes (T1D).

No relationship between infection and development was observed after screening more than 50,000 youth patients in diverse populations of Colorado and Bavaria, Germany.

“Long-term follow-up of persons with preexisting 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.

The increased incidence of clinical diabetes has been reported in children with prior COVID-19 infection. Thus, Rewers and colleagues noted it may be plausible that the virus may trigger autoimmune response to the islets or hasten metabolic decompensation in individuals with established islet autoimmunity.

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

Autoantibody-negative children were additionally followed-up with after detection of SARS-CoV-2 antibodies with blood sample collection every 3 months in Bavaria.

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

The study outcomes included the presence of multiple or single high-affinity islet autoantibodies that carry a 50% and 30% risk of progression to clinical diabetes in 5 years, respectively. Investigators used multivariable logistic regression to assess independent associations between previous infection and islet autoimmunity and testing for interactions by study site.

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

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

Investigators noted the prevalence of multiple or single high-affinity islet autoantibodies did not significant differ between youths with previous SARS-CoV-2 infection compared to those without previous infection in Colorado (1.18% vs 0.91%, P = .43) or Bavaria (0.42% vs 0.41%; P = .88).

The findings additionally suggest previous infection was not significantly associated with the presence of multiple islet autoantibodies (odds ratio, 1.06 [95% CI, 0.59 - 1.80]; P = .83) or a single high-affinity islet autoantibody (odds ratio, 1.34 [95% CI, 0.70 - 2.44]; P = .36) after controlling for confounders.

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

Rewers noted the limitations of the study included the low prevalence of autoantibodies, weakening the ability to detect an increase in risk associated with SARS-CoV-2 infection. As well, the cross-sectional design did not allow determination of the time 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.