Clinical and Inflammatory Predictors of Neurocognitive Decline in Long COVID: A Two-Year Longitudinal Study with Propensity Score Matching

Background and Objectives: Neurological complications of SARS-CoV-2 infection frequently impair patients’ long-term quality of life. This study aimed to identify clinical and laboratory risk factors—including inflammatory markers and micronutrients—for the occurrence or worsening of neurocognitive disorders in long COVID patients. Materials and Methods: In this prospective observational study, patients presenting with long COVID neurological manifestations were stratified by baseline MoCA score into two groups (≥23 and <23). Clinical, laboratory (inflammatory markers, 25-hydroxy vitamin D, vitamin B12, folic acid), and neuroimaging assessments (global cortical atrophy scale, Fazekas score) were performed over 24 months. Propensity score matching (PSM) for age, gender, and neurological comorbidities yielded 54 patients per group. Results: In the MoCA ≥ 23 group, significant predictors of cognitive decline included severe COVID-19 (OR = 2.211, 95% CI = 1.819–5.973, p = 0.012), autoimmune comorbidities (OR = 1.676, 95% CI = 1.191–2.390, p = 0.043), and elevated neutrophil-to-lymphocyte ratio (NLR; OR = 1.586, 95% CI = 1.431–2.122, p = 0.011). In the MoCA < 23 group, independent predictors were diabetes mellitus (OR = 3.021, 95% CI = 2.65–14.004, p = 0.016), autoimmune comorbidities (OR = 4.987, 95% CI = 1.412–6.033, p = 0.021), and NLR (OR = 5.944, 95% CI = 2.353–19.321, p = 0.015). Serum vitamin D levels were significantly associated with MoCA scores in both groups. Conclusions: COVID-19 severity, autoimmune comorbidities, NLR, and serum vitamin D represent key risk factors for neurocognitive decline in long COVID, highlighting potential targets for early intervention.