Divergent Inflammatory Profiles but No Predictive Biomarkers of Psychiatric Sequelae After Viral Infection: A...

Viral infections have been implicated in psychiatric outcomes through immune-mediated pathways. This 12-month prospective cohort study, designed as a pilot and hypothesis-generating investigation, 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 explored their potential predictive value. Thirty-seven patients hospitalized with viral infections and 32 healthy controls were evaluated, acknowledging the limited sample size. Psychiatric interviews and the Hospital Anxiety and Depression Scale (HADS) were used for assessment. 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 assessment was repeated. No significant differences were found in psychiatric diagnosis rates or symptom severity between infection groups, regardless of viral type or neuroinvasive capacity. However, these findings should be interpreted as preliminary given the limited sample size. Some cytokines, eg., interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), and soluble interleukin-2 receptor subunit alpha (sIL-2Rα), showed associations with individual symptoms, but these were inconsistent and did not demonstrate robust predictive value. Cluster analysis identified two distinct inflammatory profiles-one characterized by higher cytokine levels (predominantly in Coronavirus disease 2019 (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. Given the exploratory nature of the study, all results require confirmation in larger, adequately powered cohorts. Future studies should focus on composite biomarkers and systems-based models such as neuroimmune-metabolic-oxidative pathways (NIMETOX), or Immune-Inflammatory Response System (IRS)/Compensatory Immune Response System (CIRS)/Oxidative & Nitrosative Stress (O&NS) for improved predictive accuracy.