BACKGROUND: The long-term sequelae of COVID-19 remain a growing concern; however, a limited study targeting individuals with preexisting type 2 diabetes mellitus (T2DM) and Asian populations has been conducted. This large-scale, binational cohort study with extended follow-up aimed to evaluate the risk of post-acute sequelae of COVID-19 across multiple organ systems in individuals with T2DM.
METHODS: This study used binational, population-based cohorts in South Korea (K-COV-N; discovery cohort; n = 3,002,271) and Japan (JMDC; validation cohort; n = 1,125,045). All individuals aged >19 years were included from January 1, 2020, to December 31, 2022. We estimated the long-term risk of post-acute sequelae following SARS-CoV-2 infection. We defined the primary outcome as the onset of 65 diseases across 9 organ systems beyond the first 30 days after SARS-CoV-2 infection. After applying propensity score-based overlap weighting, we utilized Cox proportional hazards models to estimate adjusted hazard ratios (HRs) with 95% CIs for post-acute sequelae of COVID-19 within the weighted population. We further examined how the risk of sequelae changed over time following COVID-19 diagnosis. We also conducted multiple subgroup analyses on the severity of COVID-19, COVID-19 vaccination status, and T2DM-related complications.
RESULTS: In the overlap-weighted discovery cohort, 1,056,277 individuals with preexisting T2DM were analyzed (mean age: 58.06 years [SD, 10.02]; 39.41% females). Compared with non-infected individuals, those with SARS-CoV-2 infection showed an increased long-term risk of sequelae across eight organ systems, including cardiovascular diseases (aHR, 1.11 [95% CI, 1.09-1.13]), dermatologic conditions (aHR, 1.20 [1.10-1.31]), endocrine disorders (aHR, 1.04 [1.01-1.08]), gastrointestinal diseases (aHR, 1.11 [1.07-1.14]), hepato-biliary-pancreatic disorders (aHR, 1.07 [1.03-1.11]), kidney disorders (aHR, 1.09 [1.03-1.16]), neurological disorders (aHR, 1.11 [1.03-1.20]), and pulmonary diseases (aHR, 1.11 [1.04-1.18]). Specifically, of 65 diseases, 45 showed a significantly elevated incident risk following a COVID-19 diagnosis. The risk of sequelae was higher in individuals with moderate-to-severe COVID-19 and persisted up to 12 months post-infection, with attenuation thereafter. COVID-19 vaccination was associated with reduced sequelae risk of developing some sequelae; however, the risk was still generally higher than in non-infected individuals. Similar trends were observed in the validation cohort, where all 65 specific diseases showed significant associations with long-term sequelae.
CONCLUSION: Among individuals with preexisting T2DM, SARS-CoV-2 infection was associated with an increased risk of long-term sequelae across multiple organ systems, particularly in moderate-to-severe cases. Risks peaked within 12 months and gradually subsided thereafter, highlighting the enduring impact of COVID-19 and the need for sustained monitoring and preventive care in this high-risk population.
