Neuropathology of Severe Depression in Long COVID-19 Infection; Possible Roles for Astrocytes, Creatine Kinase and Lactate Dehydrogenase Activity

Abstract

Background: The incidence of depression has increased significantly during the COVID-19 pandemic. Some individuals infected with COVID-19 develop persistent neurological and neuropsychiatric symptoms approximately 12 weeks after the acute infection, a condition known as long COVID-19 syndrome. However, the underlying pathogenesis remains unclear. Glial fibrillary acidic protein (GFAP), creatine kinase (CK), and lactate dehydrogenase (LDH) are enzymes abundant in the central nervous system (CNS), playing important roles in neuronal energy homeostasis. Objectives: This study aimed to investigate the correlation between serum GFAP, CK, and LDH levels and depression in patients with long COVID-19 syndrome. Methods: This cross-sectional study involved 150 patients (75 males and 75 females). The Beck Depression Inventory-II (BDI-II) was used, along with standardized peripheral serum assessments. Serum GFAP, CK, and LDH levels were measured using customized direct ELISA. Data were matched by age and sex, and analyzed using Spearman non-parametric tests to assess the correlation between variables. Results: The serum level of GFAP was significantly higher in both males and females with severe depression compared to those with mild depression (282 ± 3 pg/mL, 280 ± 2.9 pg/mL, P = 0.001). The mean serum CK level was 239 ± 24.05 U/L in males and 142 ± 18.08 U/L in females (P < 0.0001). Furthermore, a significant positive correlation was found between CK serum levels and Beck scores (r = 0.33, 95% CI = 0.176 to 0.469), with a similar pattern observed for LDH (r = 0.22, 95% CI = 0.042 to 0.358). GFAP, CK, and LDH levels were higher in male patients. Conclusions: This study identified potential neurobiological mechanisms in CNS-related long COVID syndrome, suggesting that elevated astrocyte activity, along with increased serum CK and LDH levels, may contribute to the neurobiological issues seen in depressed long COVID survivors. Men appeared to be more susceptible to these changes than women. Further research is essential.