Association of SARS-CoV-2 Infection With New-Onset Type 1 Diabetes Among Pediatric Patients From 2020 to 2021

Introduction

Incidence of new-onset type 1 diabetes (T1D) increased during the COVID-19 pandemic,1 and this increase has been associated with SARS-CoV-2 infection.2 The US Centers for Disease Control and Prevention reported that pediatric patients with COVID-19 were more likely to be diagnosed with diabetes after infection, although types 1 and 2 were not separated.3 Therefore, whether COVID-19 was associated with new-onset T1D among youths remains unclear. This cohort study assessed whether there was an increase in new diagnoses of T1D among pediatric patients after COVID-19.

Methods

Data were obtained using TriNetX Analytics Platform, a web-based database of deidentified electronic health records of more than 90 million patients, from the Global Collaborative Network, which includes 74 large health care organizations across 50 US states and 14 countries with diverse representation of geographic regions, self-reported race, age, income, and insurance types.4 The MetroHealth System institutional review board deemed the study exempt because it was determined to be non–human participant research. The study followed the STROBE reporting guideline.

The study population comprised pediatric patients in 2 cohorts: (1) patients aged 18 years or younger with SARS-CoV-2 infection between March 2020 and December 2021 and (2) patients aged 18 years or younger without SARS-CoV-2 infection but with non–SARS-CoV-2 respiratory infection during the same period. SARS-CoV-2 infection was defined as described in prior studies.5 These cohorts were subdivided into groups aged 0 to 9 years and 10 to 18 years.

Cohorts were propensity score matched (1:1 using nearest-neighbor greedy matching) for demographics and family history of diabetes (Table). Risk of new diagnosis of T1D within 1, 3, and 6 months after infection were compared between matched cohorts using hazard ratios (HRs) and 95% CIs. Statistical analyses were conducted in the TriNetX Analytics Platform. Further details and analyses from the TriNetX database are given in the eMethods in the Supplement.

Results

The Table shows population characteristics before and after matching. The study population included 1 091 494 pediatric patients: 314 917 with COVID-19 and 776 577 with non–COVID-19 respiratory infections. The matched cohort included 571 256 pediatric patients: 285 628 with COVID-19 and 285 628 with non–COVID-19 respiratory infections. By 6 months after COVID-19, 123 patients (0.043%) had received a new diagnosis of T1D, but only 72 (0.025%) were diagnosed with T1D within 6 months after non–COVID-19 respiratory infection. At 1, 3, and 6 months after infection, risk of diagnosis of T1D was greater among those infected with SARS-CoV-2 compared with those with non–COVID-19 respiratory infection (1 month: HR, 1.96 [95%CI, 1.26-3.06]; 3 months: HR, 2.10 [95% CI, 1.48-3.00]; 6 months: HR, 1.83 [95% CI, 1.36-2.44]) and in subgroups of patients aged 0 to 9 years, a group unlikely to develop type 2 diabetes, and 10 to 18 years (Figure). Similar increased risks were observed among children infected with SARS-CoV-2 compared with other control cohorts at 6 months (fractures: HR, 2.09 [95% CI, 1.41- 3.10]; well child visits: HR, 2.10 [95% CI, 1.61- 2.73]).

Discussion

In this study, new T1D diagnoses were more likely to occur among pediatric patients with prior COVID-19 than among those with other respiratory infections (or with other encounters with health systems). Respiratory infections have previously been associated with onset of T1D,6 but this risk was even higher among those with COVID-19 in our study, raising concern for long-term, post–COVID-19 autoimmune complications among youths. Study limitations include potential biases owing to the observational and retrospective design of the electronic health record analysis, including the possibility of misclassification of diabetes as type 1 vs type 2, and the possibility that additional unidentified factors accounted for the association. Results should be confirmed in other populations. The increased risk of new-onset T1D after COVID-19 adds an important consideration for risk-benefit discussions for prevention and treatment of SARS-CoV-2 infection in pediatric populations.

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Accepted for Publication: August 6, 2022.

Published: September 23, 2022. doi:10.1001/jamanetworkopen.2022.33014

Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2022 Kendall EK et al. JAMA Network Open.

Corresponding Author: Rong Xu, PhD, Sears Tower T303, Center for Artificial Intelligence in Drug Discovery (rxx@case.edu); Pamela B. Davis, MD, PhD, Sears Tower T402, Center for Community Health Integration (pbd@case.edu), Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH 44106.

Author Contributions: Ms Kendall and Ms Olaker had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Kendall, Xu, Davis.

Acquisition, analysis, or interpretation of data: Kendall, Olaker, Kaelber, Xu.

Drafting of the manuscript: Kendall, Olaker.

Critical revision of the manuscript for important intellectual content: Kendall, Kaelber, Xu, Davis.

Statistical analysis: Kendall, Olaker, Xu.

Obtained funding: Xu.

Administrative, technical, or material support: All authors.

Supervision: Kaelber, Xu, Davis.

Conflict of Interest Disclosures: Dr Kaelber reported receiving grants from the National Institutes of Health during the conduct of the study. No other disclosures were reported.

Funding/Support: This study was supported by grants AG057557 (Dr Xu), AG061388 (Dr Xu), AG062272 (Dr Xu), and AG076649 (Drs Xu and Davis) from the National Institute on Aging; grant R01AA029831 (Drs Xu and Davis) from the National Institute on Alcohol Abuse and Alcoholism; grant UG1DA049435 from the National Institute on Drug Abuse, and grant 1UL1TR002548-01 from the Clinical and Translational Science Collaborative of Cleveland.

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.

Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.