HbA1c and leukocyte mtDNA levels as major factors associated with post-COVID-19 syndrome in type 2 diabetes patients

Post-COVID-19 syndrome (PCS) is an emerging health problem in people recovering from COVID-19 infection within the past 3-6 months. The current study aimed to define the predictive factors of PCS development by assessing the mitochondrial DNA (mtDNA) levels in blood leukocytes, inflammatory markers and HbA1c in type 2 diabetes patients (T2D) with regard to clinical phenotype, gender, and biological age. In this case-control study, 65 T2D patients were selected. Patients were divided into 2 groups depending on PCS presence: the PCS group (n = 44) and patients who did not develop PCS (n = 21) for up to 6 months after COVID-19 infection. HbA1c and mtDNA levels were the primary factors linked to PCS in different models. We observed significantly lower mtDNA content in T2D patients with PCS compared to those without PCS (1.26 ± 0.25 vs. 1.44 ± 0.24; p = 0.011). In gender-specific and age-related analyses, the mt-DNA amount did not differ significantly between the subgroups. According to the stepwise multivariate logistic regression analysis, low mtDNA content and HbA1c were independent variables associated with PCS development, regardless of oxygen, glucocorticoid therapy and COVID-19 severity. The top-performing model for PCS prediction was the gradient boosting machine (GBM). HbA1c and mtDNA had a notably greater influence than the other variables, indicating their potential as prognostic biomarkers.