Impact of SARS-CoV-2 Infection on Disease Trajectory in Youth with T1D: An EHR-Based Cohort Study from the RECOVER Program

Abstract

Background. Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) is associated with worsening diabetes trajectory. It is unknown whether PASC in children with type 1 diabetes (T1D) manifests as worsening diabetes trajectory. Objective. To explore the association between SARS-CoV-2 infection (COVID-19) and T1D-related healthcare utilization (for diabetic ketoacidosis (DKA) or severe hypoglycemia (SH)) or hemoglobin (Hb) A1c trajectory. Methods: We included children <21 years with T1D and ≥1 HbA1c prior to cohort entry, which was defined as COVID-19 (positive diagnostic test or diagnosis code for COVID-19, multisystem inflammatory syndrome in children, or PASC) or a randomly selected negative test for those who were negative throughout the study period (Broad Cohort). A subset with ≥1 HbA1c value from 28 to 275 days after cohort entry (Narrow Cohort) was included in the trajectory analysis. Propensity score-based matched cohort design followed by weighted Cox regression was used to evaluate the association of COVID-19 with healthcare utilization ≥28 days after cohort entry. Generalized estimating equation (GEE) models were used to measure change in HbA1c in the Narrow Cohort. Results. From March 01, 2020 to June 22, 2022, 2,404 and 1,221 youth met entry criteria for the Broad and Narrow Cohorts, respectively. The hazard ratio for utilization was (HR 1.45 (95% CI: 0.97, 2.16)). In the Narrow Cohort, the rate of change (slope) of HbA1c increased 91-180 days after cohort entry for those with COVID-19 (0.138 vs. -0.002, p=0.172). Beyond 180 days, greater declines in HbA1c were observed in the positive cohort (-0.104 vs. 0.008 per month, p=0.024). Conclusion. While a trend toward worse outcomes following COVID-19 in T1D patients was observed, these findings were not statistically significant. Continued clinical monitoring of youth with T1D following COVID-19 is warranted.