To the Editor: An increased incidence of pediatric type 1 diabetes during the coronavirus disease 2019 (Covid-19) pandemic has been widely reported.1-4 We conducted a study involving 4586 children 9 to 15 years of age from the United States, Sweden, Finland, and Germany.5 The children were followed from January 2020 (prepandemic) through December 2021 (pandemic) and were tested every 3 months for type 1 diabetes if they had islet autoantibodies (440 participants) and every 6 months if they did not (4146 participants) (Table 1). The children were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (infection) and spike (vaccination) antibodies at each follow-up visit.
Table 1. Characteristics of Children Tested for Covid-19 and followed from January 1, 2020, to December 31, 2021.
| Characteristic | All Children |
Children with Covid-19 |
|---|---|---|
| no. | no. (%) | |
| Sex | ||
| Female | 2264 | 340 (15.0) |
| Male | 2322 | 365 (15.7) |
| Age — yr | ||
| 9 | 161 | 29 (18.0) |
| 10 | 1059 | 190 (17.9) |
| 11 | 934 | 153 (16.4) |
| 12 | 974 | 177 (18.2) |
| 13 | 840 | 129 (15.4) |
| 14 | 590 | 27 (4.6) |
| 15 | 28 | 0 |
| Country | ||
| United States | 1829 | 351 (19.2) |
| Finland | 1053 | 27 (2.6) |
| Germany | 233 | 10 (4.3) |
| Sweden | 1471 | 317 (21.5) |
| First-degree relative with type 1 diabetes | ||
| No | 4066 | 632 (15.5) |
| Yes | 520 | 73 (14.0) |
| Body-mass index* | ||
| ≤15 | 416 | 63 (15.1) |
| 16–20 | 2549 | 395 (15.5) |
| 21–25 | 1058 | 165 (15.6) |
| 26–30 | 275 | 40 (14.5) |
| 31–35 | 65 | 11 (16.9) |
| 36–40 | 20 | 6 (30.0) |
| 41–45 | 3 | 0 |
| Missing data | 200 | 19 (9.5) |
| Persistent, confirmed positivity for islet autoantibodies at study start | ||
| No | 4146 | 623 (15.0) |
| Yes | 440 | 82 (18.6) |
The body-mass index is the weight in kilograms divided by the square of the height in meters. Covid-19 denotes coronavirus disease 2019.
Of the 4586 children, 705 (15.4%) had a positive test for SARS-CoV-2 nucleocapsid antibodies — 623 of the 4146 children without islet autoantibodies (15.0%; 95% confidence interval [CI], 13.9 to 16.1) and 82 of the 440 children with islet autoantibodies (18.6%; 95% CI, 15.0 to 22.3). Among the 4146 children without islet autoantibodies, seroconversion to persistent, confirmed positivity for islet autoantibodies occurred in 40 (1.0%; 95% CI, 0.7 to 1.3). Only 5 of these 40 children had nucleocapsid antibodies, which appeared after seroconversion. The remaining 35 children never had a positive test for nucleocapsid antibodies. Hence, seroconversion did not occur in any children without islet autoantibodies who had had SARS-CoV-2 infection (0 of 623 children); seroconversion occurred only in children without islet autoantibodies who had not had SARS-CoV-2 infection (40 of 3523 children [1.1%; 95% CI, 0.8 to 1.5]).
A total of 45 children received a diagnosis of type 1 diabetes during the 24-month follow-up. Five children received a diagnosis before they had a positive test for SARS-CoV-2 nucleocapsid antibodies. One child received a diagnosis of type 1 diabetes after the detection of SARS-CoV-2 infection. The remaining 39 children with type 1 diabetes never had a positive test for nucleocapsid antibodies: 30 were never vaccinated, 2 were vaccinated before the diagnosis of type 1 diabetes, and 4 were vaccinated after the diagnosis; 3 were not tested. There was no evidence showing that the number of children in whom seroconversion to persistent islet-autoantibody positivity occurred was greater among those with SARS-CoV-2 infection, even with the inclusion of samples obtained after the study period if the last sample within the study period was positive for Covid-19 or islet autoantibodies. The number of children who received a diagnosis of type 1 diabetes did not differ between those with and those without SARS-CoV-2 infection. All the children were seen either four or eight times over the 2 years, depending on islet-autoantibody status.
Despite the plausibility of a biologic connection, systematic testing for the virus and type 1 diabetes in a prospective, multinational cohort of children before and during the pandemic did not show that Covid-19 precipitated type 1 diabetes, in contrast to studies in which Covid-19 testing was not performed. These findings must be tempered somewhat because they reflect a narrow age range among children with an increased genetic risk of type 1 diabetes (representativeness of the study cohort is shown in Table S1 in the Supplementary Appendix, available with the full text of this letter at NEJM.org). Longer follow-up may provide additional insights.
Supplementary Appendix
Disclosure Forms
The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
The data sets generated and analyzed during the current study will be made available in the National Institute of Diabetes and Digestive and Kidney Diseases Central Repository at https://repository.niddk.nih.gov/studies/teddy.
Footnotes
Supported by grants U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, UC4 DK117483, U01 DK124166, and U01 DK128847 and Contract No. HHSN267200700014C from the National Institute of Diabetes and Digestive and Kidney Diseases, in collaboration with the National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, the Centers for Disease Control and Prevention, and the JDRF and supported in part by Clinical and Translational Science Awards from the National Center for Advancing Translational Sciences to the University of Florida (UL1 TR000064) and the University of Colorado (UL1 TR002535).
Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org.
References
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