Neurofunctional Outcomes After Pediatric SARS-CoV-2 Infection and Acute Interferon-Related Gene Expression: An Exploratory Observational Pilot Study

Long-term neurofunctional outcomes after pediatric SARS-CoV-2 infection remain incompletely understood, particularly in relation to acute antiviral immune responses. This exploratory observational pilot study assessed neurofunctional performance approximately six months after infection and its association with acute nasopharyngeal interferon-related gene expression. Sixteen children aged 3–10 years with RT-qPCR-confirmed mild COVID-19 underwent cognitive, gross motor, and functional exercise assessments. Transcript abundance of IFNA2, IFNB1, IFNL2/3, IFI6, and OAS2 was evaluated by qPCR. Five children (31.25%) scored below the age-specific MMSE cutoff, and five of 14 children (35.71%) had below-average TGMD-2 performance. Thirteen completed the ISWT, achieving 53.95 ± 13.55% of the individually predicted distance. IFNB1, IFI6, and OAS2 were detected in all acute-phase samples, whereas IFNA2 and IFNL2/3 were not detected. No statistically significant associations were identified between the detected transcripts and subsequent neurofunctional outcomes. Although the small sample size, absence of pre-infection assessments, and lack of an uninfected comparison group limit interpretation of the findings, this pilot study provides preliminary descriptive data integrating acute mucosal interferon-related gene expression with subsequent neurofunctional assessments in children, supporting further investigation in larger, controlled cohorts.