Is T1D risk greater in children with COVID than other respiratory infections?

Children with a previous COVID-19 infection seemed more likely to develop type 1 diabetes (T1D) than children who had other respiratory infections during the pandemic, a cohort study showed.

In this propensity score matching analysis of over 500,000 pediatric patients, those previously infected with SARS-CoV-2 were at greater risk of a new T1D diagnosis than other respiratory infections at the following time points after 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)

Similar risks were seen for the SARS-CoV-2 group compared to other control cohorts who had contact with the healthcare system at 6 months, such as those who had fractures (HR 2.09, 95% CI 1.41-3 ,10), Rong Xu, PhD, of Case Western Reserve University School of Medicine in Cleveland, and colleagues reported in a research letter published in JAMA network open.

In a subgroup analysis that divided the children into two age groups—ages 0 to 9 years and ages 10 to 18—both groups were found to be at higher risk at 6 months:

• Age 0-9: HR 1.73 (95% CI 1.02-2.94)
• Age 10-18: HR 2.18 (95% CI 1.57-3.03)

“Respiratory tract infections have previously been associated with the occurrence of T1D, but this risk was even higher in those with COVID-19 in our study, raising concerns about long-term autoimmune complications after COVID-19 in adolescents,” they wrote.

“The increased risk of emerging T1D after COVID-19 adds an important consideration for risk-benefit discussions on prevention and treatment of SARS-CoV-2 infection in pediatric populations,” they concluded.

A surge in T1D cases has been seen in children during the pandemic, Xu’s group noted. The CDC reported that children diagnosed with SARS-CoV-2 were more likely to develop diabetes but did not differentiate between type 1 and type 2. However, other studies have suggested that more evidence is needed to confirm the link.

“COVID-19 can have significant effects on multiple organ systems in children, including the pancreas and immune system,” Xu said MedPage today.

As for the next research steps, “first, we want to follow the cohorts longer to see if the increased risk of T1D is transient or persistent,” Xu noted. “Second, [we would like to] quickly evaluate whether existing drugs (e.g., antivirals, anti-inflammatory drugs) can be repurposed to treat COVID-19-associated T1D.”

“Third, we need to investigate whether COVID-19-triggered T1D differs from traditional T1D,” he added. “Fourth, we want to investigate whether COVID-19 is also associated with new diagnoses of type 2 diabetes in children.”

For this study, Xu and colleagues examined electronic medical record data from the Global Collaborative Network of 1,091,494 pediatric patients with COVID-19 (n=314,917) or non-COVID respiratory infections (n=776,577) at 74 centers in 50 US states and 14 countries from March 2020 to December 2021. They matched 285,628 patients from each infection group 1:1 for family history of diabetes and demographics. Patients were further divided into younger and older age groups.

The mean patient age after matching was 9 years in both groups. Over half of all patients were white and half were boys. Only 1-2% had a family history of diabetes.

6 months after infection, 0.04% of the COVID-19 group received a new diagnosis of T1D compared to 0.03% of the non-COVID group.

Xu and colleagues noted the observational, retrospective design of their study, which may have introduced potential bias. In addition, the use of electronic medical records increased the risk of diagnostic misclassification.