Divergent Inflammatory Profiles but No Predictive Biomarkers of Psychiatric Sequelae After Viral Infection: A 12-Month Cohort Study

Viral infections have been implicated in psychiatric outcomes through immune-mediated pathways. This 12-month prospective cohort study compared psychiatric symptoms and inflammatory cytokine profiles in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), hepatitis C virus (HCV), and tick-borne encephalitis virus (TBEV), and assessed their predictive value. 37 patients hospitalized with viral infections and 32 healthy controls were evaluated using psychiatric interviews and the Hospital Anxiety and Depression Scale (HADS). The study was divided into two stages. In Stage 1, during the acute infection, a psychiatric assessment was conducted and cytokine levels were measured in the patients’ blood. In Stage 2, one year later, the psychiatric as-sessment was repeated. No significant differences were found in psychiatric diagnosis rates or symptom severity between infection groups, regardless of viral type or neu-roinvasive capacity. Some cytokines (eg., IL-1β, TNF-α, IL-10, and sIL-2Rα) showed as-sociations with individual symptoms, but these were inconsistent and not predictive. Cluster analysis identified two distinct inflammatory profiles - one characterized by higher cytokine levels (predominantly in COVID-19 and TBEV cases) and the other by lower cytokine levels (mostly in HCV and controls). However, different cytokine profiles did not correspond to clinical outcomes. The results suggest that psychiatric sequelae after viral infections are not directly driven by specific cytokines or infection type but rather emerge from a complex interaction of immune, psychological, and environmental factors. Single cytokine measurement is insufficient and cannot be used as a tool for assessing the risk of developing psychiatric disorders. Future studies should focus on composite bi-omarkers and systems-based models such as neuroimmune-metabolic-oxidative path-ways (NIMETOX), Immune-Inflammatory Response System (IRS)/ Compensatory Im-mune Response System (CIRS)/ Oxidative & Nitrosative Stress (O&NS) for improved predictive accuracy.