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SARS-CoV-2 Infection and Development of Islet Autoimmunity in Early Childhood

Lugar, Marija ; Eugster, Anne ; Achenbach, Peter ; von dem Berge, Thekla ; Berner, Reinhard ; Besser, Rachel E J ; Casteels, Kristina ; Elding Larsson, Helena LU ; Gemulla, Gita and Kordonouri, Olga , et al. (2023) In JAMA 330(12).
Abstract

IMPORTANCE: The incidence of diabetes in childhood has increased during the COVID-19 pandemic. Elucidating whether SARS-CoV-2 infection is associated with islet autoimmunity, which precedes type 1 diabetes onset, is relevant to disease etiology and future childhood diabetes trends.

OBJECTIVE: To determine whether there is a temporal relationship between SARS-CoV-2 infection and the development of islet autoimmunity in early childhood.

DESIGN, SETTING, AND PARTICIPANTS: Between February 2018 and March 2021, the Primary Oral Insulin Trial, a European multicenter study, enrolled 1050 infants (517 girls) aged 4 to 7 months with a more than 10% genetically defined risk of type 1 diabetes. Children were followed up through... (More)

IMPORTANCE: The incidence of diabetes in childhood has increased during the COVID-19 pandemic. Elucidating whether SARS-CoV-2 infection is associated with islet autoimmunity, which precedes type 1 diabetes onset, is relevant to disease etiology and future childhood diabetes trends.

OBJECTIVE: To determine whether there is a temporal relationship between SARS-CoV-2 infection and the development of islet autoimmunity in early childhood.

DESIGN, SETTING, AND PARTICIPANTS: Between February 2018 and March 2021, the Primary Oral Insulin Trial, a European multicenter study, enrolled 1050 infants (517 girls) aged 4 to 7 months with a more than 10% genetically defined risk of type 1 diabetes. Children were followed up through September 2022.

EXPOSURE: SARS-CoV-2 infection identified by SARS-CoV-2 antibody development in follow-up visits conducted at 2- to 6-month intervals until age 2 years from April 2018 through June 2022.

MAIN OUTCOMES AND MEASURES: The development of multiple (≥2) islet autoantibodies in follow-up in consecutive samples or single islet antibodies and type 1 diabetes. Antibody incidence rates and risk of developing islet autoantibodies were analyzed.

RESULTS: 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 (range, 6-25 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 (95% CI, 1.6-7.7; P = .002). The incidence rate of islet autoantibodies was 3.5 (95% CI, 2.2-5.1) per 100 person-years in children without SARS-CoV-2 antibodies and 7.8 (95% CI, 5.3-19.0) per 100 person-years in children with SARS-CoV-2 antibodies (P = .02). 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; 95% CI, 1.5-18.3; P = .009).

CONCLUSION AND RELEVANCE: In young children with high genetic risk of type 1 diabetes, SARS-CoV-2 infection was temporally associated with the development of islet autoantibodies.

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organization
publishing date
type
Contribution to journal
publication status
published
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in
JAMA
volume
330
issue
12
article number
1151
pages
10 pages
publisher
American Medical Association
external identifiers
  • scopus:85172020940
  • pmid:37682551
ISSN
0098-7484
DOI
10.1001/jama.2023.16348
language
English
LU publication?
yes
id
9c7e0f0f-7442-411e-a0c2-32bad59098b3
date added to LUP
2023-09-20 10:50:51
date last changed
2024-04-14 04:45:46
@article{9c7e0f0f-7442-411e-a0c2-32bad59098b3,
  abstract     = {{<p>IMPORTANCE: The incidence of diabetes in childhood has increased during the COVID-19 pandemic. Elucidating whether SARS-CoV-2 infection is associated with islet autoimmunity, which precedes type 1 diabetes onset, is relevant to disease etiology and future childhood diabetes trends.</p><p>OBJECTIVE: To determine whether there is a temporal relationship between SARS-CoV-2 infection and the development of islet autoimmunity in early childhood.</p><p>DESIGN, SETTING, AND PARTICIPANTS: Between February 2018 and March 2021, the Primary Oral Insulin Trial, a European multicenter study, enrolled 1050 infants (517 girls) aged 4 to 7 months with a more than 10% genetically defined risk of type 1 diabetes. Children were followed up through September 2022.</p><p>EXPOSURE: SARS-CoV-2 infection identified by SARS-CoV-2 antibody development in follow-up visits conducted at 2- to 6-month intervals until age 2 years from April 2018 through June 2022.</p><p>MAIN OUTCOMES AND MEASURES: The development of multiple (≥2) islet autoantibodies in follow-up in consecutive samples or single islet antibodies and type 1 diabetes. Antibody incidence rates and risk of developing islet autoantibodies were analyzed.</p><p>RESULTS: 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 (range, 6-25 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 (95% CI, 1.6-7.7; P = .002). The incidence rate of islet autoantibodies was 3.5 (95% CI, 2.2-5.1) per 100 person-years in children without SARS-CoV-2 antibodies and 7.8 (95% CI, 5.3-19.0) per 100 person-years in children with SARS-CoV-2 antibodies (P = .02). Islet autoantibody risk in children with SARS-CoV-2 antibodies was associated with younger age (&lt;18 months) of SARS-CoV-2 antibody development (HR, 5.3; 95% CI, 1.5-18.3; P = .009).</p><p>CONCLUSION AND RELEVANCE: In young children with high genetic risk of type 1 diabetes, SARS-CoV-2 infection was temporally associated with the development of islet autoantibodies.</p>}},
  author       = {{Lugar, Marija and Eugster, Anne and Achenbach, Peter and von dem Berge, Thekla and Berner, Reinhard and Besser, Rachel E J and Casteels, Kristina and Elding Larsson, Helena and Gemulla, Gita and Kordonouri, Olga and Lindner, Annett and Lundgren, Markus and Müller, Denise and Oltarzewski, Mariusz and Rochtus, Anne and Scholz, Marlon and Szypowska, Agnieszka and Todd, John A and Ziegler, Anette-Gabriele and Bonifacio, Ezio}},
  issn         = {{0098-7484}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{12}},
  publisher    = {{American Medical Association}},
  series       = {{JAMA}},
  title        = {{SARS-CoV-2 Infection and Development of Islet Autoimmunity in Early Childhood}},
  url          = {{http://dx.doi.org/10.1001/jama.2023.16348}},
  doi          = {{10.1001/jama.2023.16348}},
  volume       = {{330}},
  year         = {{2023}},
}