Physical symptoms and inflammatory levels characterize post-COVID-19 depressive episodes compared to non-post-COVID-19 depression

Major depressive episodes (MDE) following COVID-19 have been described in approximately 30 % of cases. A clinical picture characterized by physical and cognitive symptoms with underlying immune-inflammatory changes has been reported. However, a comparison of post-COVID-19 MDE with non-post-COVID-19 depression is still lacking. This study aims to characterize 209 patients with MDE, post-COVID-19 vs. non-post-COVID-19, focusing on physical and cognitive symptomatology evaluated through Hamilton Depression (HDRS) and Anxiety Rating Scales (HARS), Digit Symbol Substitution Test (DSST), Perceived Deficits Questionnaire-Depression 5-items (PDQ-D5). Inflammatory levels were assessed with blood count-derived indexes. Post-COVID-19 group (46.9 % of patients) displayed higher rates of first-onset depressive episodes (p = 0.001), an older age at onset (p = 0.006), more physical and cognitive features according to subitems of HDRS (p = 0.001), HARS (p < 0.001), and PDQ-D5 scores (p = 0.019), as well as higher inflammatory indexes (p < 0.001). Logistic regression showed a significant association of post-COVID-19 MDE with physical symptomatology (p = 0.02) and Systemic Immune-Inflammatory Index (p = 0.04). Receiver Operating Characteristic (ROC) curves displayed a discriminative potential for this association (AUC = 0.921). These results highlight the specific clinical presentation of post-COVID-19 MDE, with prominent physical symptoms and increased inflammation levels, suggesting that a more careful characterization might inform personalized interventions and promote full functional recovery in these patients.