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SARS-CoV-2 Infections and Presymptomatic Type 1 Diabetes Autoimmunity in Children and Adolescents From Colorado, USA, and Bavaria, Germany

Educational Objective
To identify the key insights or developments described in this article
1 Credit CME

An increased incidence of clinical diabetes has been reported in children with previous COVID-19.1,2 It is plausible that the virus may trigger autoimmune response to the islets or hasten metabolic decompensation in persons with already established islet autoimmunity. We tested the hypothesis that previous SARS-CoV-2 infection was associated with autoimmunity, which predicts future type 1 diabetes.

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Article Information

Accepted for Publication: July 27, 2022.

Published Online: August 5, 2022. doi:10.1001/jama.2022.14092

Corresponding Author: Marian Rewers, MD, PhD, Barbara Davis Center for Diabetes, University of Colorado School of Medicine, 1775 Aurora Ct, B-140, Aurora, CO 80045 (marian.rewers@cuanschutz.edu).

Author Contributions: Dr Rewers had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Rewers, Bonifacio, Geno Rasmussen, Ziegler.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Rewers, Geno Rasmussen, Ziegler.

Critical revision of the manuscript for important intellectual content: Bonifacio, Ewald, Geno Rasmussen, Jia, Pyle, Ziegler.

Statistical analysis: Geno Rasmussen, Pyle, Ziegler.

Obtained funding: Rewers, Ziegler.

Administrative, technical, or material support: Rewers, Ewald, Geno Rasmussen, Jia, Ziegler.

Supervision: Rewers, Bonifacio.

Other - Measurement of antibodies: Bonifacio.

Conflict of Interest Disclosures: None reported.

Funding/Support: The ASK Study (3-SRA-2018-564-M-N) is funded by JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, and Janssen Research and Development LLC. Additional support came from the Courtenay C. and Lucy Patten Davis Foundation and the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases (University of Colorado Diabetes Research Center grant DK116073). The Fr1da Study was supported by grants from LifeScience-Stiftung (HMGU 2014.01 and HMGU 2016.01), Juvenile Diabetes Research Foundation International (1-SRA-2014-310-M-R, 3-SRA-2015-72-M-R, 3-SRA-2019-718-Q-R), the Bavarian State Ministry of Health and Care (Gesund.Leben.Bayern, LP00228), The Leona M. and Harry B. Helmsley Charitable Trust (G-1911-03274), and the German Center for Diabetes Research (DZD e.V.). This work was supported by a grant from the German Federal Ministry of Education and Research (FKZ01KX1818).

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Group Information: The members of the ASK Study Group can be found at https://www.askhealth.org/about-us and the Fr1da Study Group at https://www.typ1diabetes-frueherkennung.de/informationen-fuer-aerzte/the-fr1da-study-group.html.

Additional Contributions: We thank Brigitte I. Frohnert, MD, PhD, Hanan Shorrosh, BS, Kimber Simmons, MD, Marisa Stahl, MD, Andrea K. Steck, MD, and Liping Yu, MD (Barbara Davis Center University of Colorado, Aurora), Peter Achenbach, MD, Marlon Scholz, CTA, and Franziska Voss, MS (Institute of Diabetes Research Helmholtz Munich, German Research Center for Environmental Health, Munich, Germany), and Esra Karapinar, MD (Technical University Munich, School of Medicine, Forschergruppe Diabetes at Klinikum rechts der Isar, Munich, Germany), for their contributions and critical review of the manuscript as well as other members of the ASK Study Group and Fr1da Study Group. They were supported by the ASK and Fr1da studies.

Barrett  CE , Koyama  AK , Alvarez  P ,  et al.  Risk for newly diagnosed diabetes >30 days after SARS-CoV-2 infection among persons aged <18 years—United States, March 1, 2020-June 28, 2021.   MMWR Morb Mortal Wkly Rep. 2022;71(2):59-65. doi:10.15585/mmwr.mm7102e2PubMedGoogle ScholarCrossref
Kamrath  C , Rosenbauer  J , Eckert  AJ ,  et al.  Incidence of type 1 diabetes in children and adolescents during the COVID-19 pandemic in Germany: results from the DPV Registry.   Diabetes Care. 2022;dc210969. doi:10.2337/dc21-0969PubMedGoogle ScholarCrossref
McQueen  RB , Geno Rasmussen  C , Waugh  K ,  et al.  Cost and cost-effectiveness of large-scale screening for type 1 diabetes in Colorado.   Diabetes Care. 2020;43(7):1496-1503. doi:10.2337/dc19-2003PubMedGoogle ScholarCrossref
Ziegler  AG , Kick  K , Bonifacio  E ,  et al; Fr1da Study Group.  Yield of a public health screening of children for islet autoantibodies in Bavaria, Germany.   JAMA. 2020;323(4):339-351. doi:10.1001/jama.2019.21565PubMedGoogle ScholarCrossref
Jia  X , Gesualdo  P , Geno Rasmussen  C ,  et al.  Prevalence of SARS-CoV-2 antibodies in children and adults with type 1 diabetes.   Diabetes Technol Ther. 2021;23(7):517-521. doi:10.1089/dia.2020.0609PubMedGoogle ScholarCrossref
Hippich  M , Holthaus  L , Assfalg  R ,  et al.  A public health antibody screening indicates a 6-fold higher SARS-CoV-2 exposure rate than reported cases in children.   Med (N Y). 2021;2(2):149-163.e4. doi:10.1016/j.medj.2020.10.003PubMedGoogle ScholarCrossref
AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
  • 1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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